18 research outputs found
A tau homeostasis signature is linked with the cellular and regional vulnerability of excitatory neurons to tau pathology.
Excitatory neurons are preferentially impaired in early Alzheimer's disease but the pathways contributing to their relative vulnerability remain largely unknown. Here we report that pathological tau accumulation takes place predominantly in excitatory neurons compared to inhibitory neurons, not only in the entorhinal cortex, a brain region affected in early Alzheimer's disease, but also in areas affected later by the disease. By analyzing RNA transcripts from single-nucleus RNA datasets, we identified a specific tau homeostasis signature of genes differentially expressed in excitatory compared to inhibitory neurons. One of the genes, BCL2-associated athanogene 3 (BAG3), a facilitator of autophagy, was identified as a hub, or master regulator, gene. We verified that reducing BAG3 levels in primary neurons exacerbated pathological tau accumulation, whereas BAG3 overexpression attenuated it. These results define a tau homeostasis signature that underlies the cellular and regional vulnerability of excitatory neurons to tau pathology
Protein Signature of Lung Cancer Tissues
Lung cancer remains the most common cause of cancer-related mortality. We applied a highly multiplexed proteomic technology (SOMAscan) to compare protein expression signatures of non small-cell lung cancer (NSCLC) tissues with healthy adjacent and distant tissues from surgical resections. In this first report of SOMAscan applied to tissues, we highlight 36 proteins that exhibit the largest expression differences between matched tumor and non-tumor tissues. The concentrations of twenty proteins increased and sixteen decreased in tumor tissue, thirteen of which are novel for NSCLC. NSCLC tissue biomarkers identified here overlap with a core set identified in a large serum-based NSCLC study with SOMAscan. We show that large-scale comparative analysis of protein expression can be used to develop novel histochemical probes. As expected, relative differences in protein expression are greater in tissues than in serum. The combined results from tissue and serum present the most extensive view to date of the complex changes in NSCLC protein expression and provide important implications for diagnosis and treatment
Biological Earth observation with animal sensors
Space-based tracking technology using low-cost miniature tags is now delivering data on fine-scale animal movement at near-global scale. Linked with remotely sensed environmental data, this offers a biological lens on habitat integrity and connectivity for conservation and human health; a global network of animal sentinels of environmen-tal change
The design and construction of dams; including masonry, earth, rock-fill, and timber structures, also the principal types of movable dams,
"The first part of this work was published in 1888 as a treatise on "The design and construction of masonry dams.'"--Pref. to 4th. ed., p. [v]Mode of access: Internet
Early Neolithic genomes from the eastern Fertile Crescent
We sequenced Early Neolithic genomes from the Zagros region of Iran (eastern Fertile Crescent), where some of the earliest evidence for farming is found, and identify a previously uncharacterized population that is neither ancestral to the first European farmers nor has contributed significantly to the ancestry of modern Europeans. These people are estimated to have separated from Early Neolithic farmers in Anatolia some 51- 77,000 years ago and show affinities to modern day Pakistani and Afghan populations, but particularly to Iranian Zoroastrians. We conclude that multiple, genetically differentiated hunter-gatherer populations adopted farming in SW-Asia, that components of pre-Neolithic population structure were preserved as farming spread into neighboring regions, and that the Zagros region was the cradle of eastward expansion