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Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging. Systematic characterization of longitudinal tau variability in human Alzheimer’s disease using an unbiased subtyping algorithm reveals four trajectories of tau deposition with distinct clinical features.

Activation of ATP-Sensitive K + Channels in the Ventromedial Hypothalamus Amplifies Counterregulatory Hormone Responses to Hypoglycemia in Normal and Recurrently Hypoglycemic Rats Rory J. McCrimmon , Mark L. Evans , Xiaoning Fan , Ewan C. McNay , Owen Chan , Yuyan Ding , Wanling Zhu , Dorte X. Gram 2 and Robert S. Sherwin 1 Department of Internal Medicine and Endocrinology, Yale University School of Medicine, New Haven, Connecticut 2 Pharmacology Research 3, Novo Nordisk, Māløv, Denmark Address correspondence and reprint requests to Rory J. McCrimmon, MD, Yale University School of Medicine, Section of Endocrinology, 300 Cedar St., P.O. Box 208020, New Haven, CT 06520-8020. E-mail: rory.mccrimmon{at}yale.edu Abstract The mechanism(s) by which glucosensing neurons detect fluctuations in glucose remains largely unknown. In the pancreatic β-cell, ATP-sensitive K + channels (K ATP channels) play a key role in glucosensing by providing a link between neuronal metabolism and membrane potential. The present study was designed to determine in vivo whether the pharmacological opening of ventromedial hypothalamic K ATP channels during systemic hypoglycemia would amplify hormonal counterregulatory responses in normal rats and those with defective counterregulation arising from prior recurrent hypoglycemia. Controlled hypoglycemia (∼2.8 mmol/l) was induced in vivo using a hyperinsulinemic (20 mU · kg −1 · min −1 ) glucose clamp technique in unrestrained, overnight-fasted, chronically catheterized Sprague-Dawley rats. Immediately before the induction of hypoglycemia, the rats received bilateral ventromedial hypothalamic microinjections of either the potassium channel openers (KCOs) diazoxide and NN414 or their respective controls. In normal rats, both KCOs amplified epinephrine and glucagon counterregulatory responses to hypoglycemia. Moreover, diazoxide also amplified the counterregulatory responses in a rat model of defective hormonal counterregulation. Taken together, our data suggest that the K ATP channel plays a key role in vivo within glucosensing neurons in the ventromedial hypothalamus in the detection of incipient hypoglycemia and the initiation of protective counterregulatory responses. We also conclude that KCOs may offer a future potential therapeutic option for individuals with insulin-treated diabetes who develop defective counterregulation. aECF, artificial extracellular fluid AUC, area under the curve GIR, glucose infusion rate KATP channel, ATP-sensitive K+ channel KCO, potassium channel opener VMH, ventromedial hypothalamus Footnotes Accepted July 27, 2005. Received February 1, 2005. DIABETES

Accurate assessment of leaf functional traits is crucial for a diverse range of applications from crop phenotyping to parameterizing global climate models. Leaf reflectance spectroscopy offers a promising avenue to advance ecological and agricultural research by complementing traditional, time-consuming gas exchange measurements. However, the development of robust hyperspectral models for predicting leaf photosynthetic capacity and associated traits from reflectance data has been hindered by limited data availability across species and environments. Here we introduce the Global Spectra-Trait Initiative (GSTI), a collaborative repository of paired leaf hyperspectral and gas exchange measurements from diverse ecosystems. The GSTI repository currently encompasses over 7500 observations from 397 species and 41 sites gathered from 36 published and unpublished studies, thereby offering a key resource for developing and validating hyperspectral models of leaf photosynthetic capacity. The GSTI database is developed on GitHub (https://github.com/plantphys/gsti, last access: 4 January 2026) and published to ESS-DIVE https://doi.org/10.15485/2530733, Lamour et al., 2025). It includes gas exchange data, derived photosynthetic parameters, and key leaf traits often associated with traditional gas exchange measurements such as leaf mass per area and leaf elemental composition. By providing a standardized repository for data sharing and analysis, we present a critical step towards creating hyperspectral models for predicting photosynthetic traits and associated leaf traits for terrestrial plants.

Samples of ash from the 18 May 1980 eruption of Mount St. Helens were collected from several locations in eastern Washington and Montana. The ash was subjected to a variety of analyses to determine its chemical, physical, mineralogical, and biological characteristics. Chemically, the ash samples were of dacitic composition. Particle size data showed bimodal distributions and differed considerably with location. However, all samples contained comparable amounts of particles less than 3.5 micrometers in diameter (respirable fraction). Mineralogically, the samples ranged from almost totally glassy to almost totally crystalline. Crystalline samples were dominated by plagioclase feldspar (andesine) and orthopyroxene (hypersthene), with smaller amounts of titanomagnetite and hornblende. All but one of the samples contained from less than 1 percent to 3 percent free crystalline silica (quartz, trydimite, or cristobalite) in both the bulk samples and 1 to 2 percent in the fractions smaller than 3.5 micrometers. The long-lived natural radionuclide content of the ash was comparable to that of crustal material; however, relatively large concentrations of short-lived radon daughters were present and polonium-210 content was inversely correlated with particle size. In vitro biological tests showed the ash to be nontoxic to alveolar macrophages, which are an important part of the lungs' natural clearance mechanism. On the basis of a substantial body of data that has shown a correlation between macrophage cytotoxicity and fibrogenicity of minerals, the ash is not predicted to be highly fibrogenic.

The behavior of business fixed investment in the United States in the 1980s is examined. A background discussion of the long-term behavior of the components of business fixed investment is provided, setting the context for the empirical analysis. A standard neoclassical model of business fixed investment is specified and estimated, with output and the cost of capital the primary explanatory variables. Simulation experiments are then conducted with a view to assessing the importance of various contributing factors--in particular tax policy--in influencing the behavior of business fixed investment during the economic expansion that began in late 1982.