A pangram is a sentence or phrase that contains each letter of an alphabetor character set at least once. A perfect pangram is an anagram of thealphabet which contains each letter exactly once. Pangram hash generates a perfect pangram hash digest consisting of aanagram permutation of a character set. Each character in the output isunique and non-repeating. Below is purely procedural source code written in the FreePascalprogramming language. Instructions and explanatory comments are locatedin the source code. A plain text source file is embedded in the PDFdocument. Additional resource files are also embedded in the PDF file.
Weight loss and hypermetabolism are early and prognostically significant features of amyotrophic lateral sclerosis (ALS) and are associated with hypothalamic atrophy and degeneration of melanin-concentrating hormone (MCH) neurons that regulate energy balance. To investigate whether MCH vulnerability arises from upstream network dysfunction, we performed whole-brain retrograde rabies tracing in SOD1G93A mice. We identified an early, selective loss of monosynaptic inputs from the zona incerta (ZI), a dopaminergic (DA)/gamma-aminobutyric acid (GABA)ergic nucleus that preceded MCH neuron degeneration. Neurochemical profiling confirmed the DA/GABAergic identity of these ZI input neurons, and ZI/DAergic neurons later degenerated. ALS-related pathology emerged early in the ZI, paralleling pathology in the motor cortex, while anterograde mapping revealed that motor cortical projections preferentially targeted the ZI, linking vulnerable motor and metabolic networks. Loss of ZI/DAergic neurons was observed in conjunction with weight loss in non-SOD1 ALS models. These findings identify the ZI as an early-affected node within hypothalamic networks and suggest that disruption of DA/GABAergic inputs to MCH neurons is associated with subsequent MCH and DA neuronal vulnerability, degeneration and metabolic imbalance in ALS.The online version contains supplementary material available at 10.1186/s40478-026-02231-z. Scekic-Zahirovic, Jelena; Antonucci, Stefano; Wiesner, Diana; Ebner, Chiara; El Hajj, Hussein; Aousji, Oumayma; Halablab, Kareen; Fan, Yiting; Zelaya, Anneka; Yartas, Gizem; Baskar, Karthik; Çakmak, E. Anastasia; Bayer, David; Sung, Hoon-Ki; Dupuis, Luc; Park, Jeehye; Roselli, Francesco
Digital speech-based assessments provide scalable tools for detecting subtle cognitive decline. Here, we investigated whether digitally derived speech-based composite score of cognition and individual speech features were associated with alterations in functional connectivity (FC) within task-related brain networks in the Alzheimer's disease spectrum, which are known to reflect cognitive performance and disease-related changes.Data were analyzed from 129 participants of the German PROSPECT-AD study, ranging from cognitively healthy individuals to those with mild cognitive impairment. Speech-based cognitive scores and speech features were derived from automated phone-administered semantic verbal fluency (SVF) and verbal learning tasks (VLT). Resting-state fMRI assessed FC, with intrinsic connectivity networks identified via independent component analysis and dual regression. Associations were examined using permutation-based voxel-wise regression, controlling for demographic and clinical covariates. Seed-to-voxel analyses were conducted to support network identification and complement findings.Greater language network connectivity in the left middle temporal gyrus was associated with increased SVF temporal cluster switching (FWE < .05, cluster size = 12 voxels, mean T = 3.86). Exploratory analyses (uncorrected p < .01) demonstrated no significant associations between cognitive composite scores and FC. However, individual SVF and VLT speech features exhibited network-specific associations across executive, language, and default mode networks, indicating exploratory yet spatially distinct connectivity patterns.Digital speech-based assessments may have limited current utility for detecting FC alterations in at-risk individuals. Further validation using complementary methodological approaches, shorter intervals between fMRI and speech assessments, and testing in independent cohorts, are essential to establish their reliability and clinical relevance for monitoring brain network changes. Li, Qingyue; Alexopoulou, Zampeta-Sofia; Dyrba, Martin; Mallick, Elisa; Tröger, Johannes; Spruth, Eike; Altenstein, Slawek; Bartels, Claudia; Glanz, Wenzel; Incesoy, Enise I; Butryn, Michaela; Kilimann, Ingo; Sodenkamp, Sebastian; Maier, Franziska; Rostamzadeh, Ayda; Osterrath, Antje; Priller, Josef; Schneider, Anja; Wiltfang, Jens; Laske, Christoph; Falkenburger, Björn; Wagner, Michael; Duezel, Emrah; Spottke, Annika; Petzold, Gabor C; Jessen, Frank; König, Alexandra; Köhler, Stefanie; Teipel, Stefan; DELCODE, DESCRIBE study groups
Triggering receptor expressed on myeloid cells 2 (TREM2) is a central regulator of microglial activity and loss-of-function coding variants are major risk factors for late onset Alzheimer's disease (LOAD). To better understand the molecular and functional changes associated with TREM2 signalling in microglia, we generated a TREM2 reporter mouse. In APP transgenic animals, bulk RNA-sequencing of isolated microglia sorted based on reporter expression highlighted TREM2 level-related changes in major immunometabolic pathways, and enrichment of genes in oxidative phosphorylation and cholesterol metabolism in microglia with increased TREM2 expression. Metabolic and lipidomic profiling of sorted microglia showed that, independent of Aβ pathology, TREM2 expression correlated with signatures consistent with increased cellular redox, energetics, and cholesterol homoeostasis. In accordance, metabolic activity correlated with phagocytic capacity. Finally, we performed chronic treatment with a TREM2 agonist antibody and identified a window of TREM2 expression where microglia are most responsive, thereby informing clinical applications of TREM2 agonists. Feiten, Astrid Feentje; Dahm, Kilian; Schlepckow, Kai; van Lengerich, Bettina; Suh, Jung H; Reifschneider, Anika; Wefers, Benedikt; Bartos, Laura M; Wind, Karin; de Weerd, Lis; Ulas, Thomas; De-Domenico, Elena; Grundschöttel, Pia; Paulusch, Stefan; Tast, Benjamin; Honda, Tamisa; Müller, Stephan A; Becker, Matthias; Khalin, Igor; Ricci, Alessio; Liesz, Arthur; Brunner, Bettina; Krenner, Claudia; Buschmann, Katrin; Nuscher, Brigitte; Spieth, Lena; Junker, Niklas; Berghoff, Stefan A; Davis, Sonnet S; Neher, Jonas J; Wurst, Wolfgang; Plesnila, Nikolaus; Lewcock, Joseph W; Simons, Mikael; Lichtenthaler, Stefan F; Di Paolo, Gilbert; Brendel, Matthias; Capell, Anja; Monroe, Kathryn M; Schultze, Joachim L; Haass, Christian
N-gated Hacker News
Gregorio Sánchez
OCTADE
Andy
Melting Pot Europa - Rss Bot
Market Designer Bot
Miss Kitty 🌈🌈🌈
Forschungszentrum DZNE