Legal Future Shock: The Role of Larger Law Firms by the End of the Century

The Growth of Large Law Firms and Its Effect on the Legal Profession and Legal Education, Symposiu

HID-1 controls formation of large dense core vesicles by influencing cargo sorting and trans-Golgi network acidification

Large dense core vesicles (LDCVs) mediate the regulated release of neuropeptides and peptide hormones. They form at the trans-Golgi network (TGN), where their soluble content aggregates to form a dense core, but the mechanisms controlling biogenesis are still not completely understood. Recent studies have implicated the peripheral membrane protein HID-1 in neuropeptide sorting and insulin secretion. Using CRISPR/Cas9, we generated HID-1 KO rat neuroendocrine cells, and we show that the absence of HID-1 results in specific defects in peptide hormone and monoamine storage and regulated secretion. Loss of HID-1 causes a reduction in the number of LDCVs and affects their morphology and biochemical properties, due to impaired cargo sorting and dense core formation. HID-1 KO cells also exhibit defects in TGN acidification together with mislocalization of the Golgi-enriched vacuolar H+-ATPase subunit isoform a2. We propose that HID-1 influences early steps in LDCV formation by controlling dense core formation at the TGN.</jats:p

A single transcription factor is sufficient to induce and maintain secretory cell architecture

We hypothesized that basic helix–loop–helix (bHLH) MIST1 (BHLHA15) is a “scaling factor” that universally establishes secretory morphology in cells that perform regulated secretion. Here, we show that targeted deletion of MIST1 caused dismantling of the secretory apparatus of diverse exocrine cells. Parietal cells (PCs), whose function is to pump acid into the stomach, normally lack MIST1 and do not perform regulated secretion. Forced expression of MIST1 in PCs caused them to expand their apical cytoplasm, rearrange mitochondrial/lysosome trafficking, and generate large secretory granules. Mist1 induced a cohort of genes regulated by MIST1 in multiple organs but did not affect PC function. MIST1 bound CATATG/CAGCTG E boxes in the first intron of genes that regulate autophagosome/lysosomal degradation, mitochondrial trafficking, and amino acid metabolism. Similar alterations in cell architecture and gene expression were also caused by ectopically inducing MIST1 in vivo in hepatocytes. Thus, MIST1 is a scaling factor necessary and sufficient by itself to induce and maintain secretory cell architecture. Our results indicate that, whereas mature cell types in each organ may have unique developmental origins, cells performing similar physiological functions throughout the body share similar transcription factor-mediated architectural “blueprints.

The Rise of the s-Process in the Galaxy

From newly-obtained high-resolution, high signal-to-noise ratio spectra the abundances of the elements La and Eu have been determined over the stellar metallicity range -3<[Fe/H]<+0.3 in 159 giant and dwarf stars. Lanthanum is predominantly made by the s-process in the solar system, while Eu owes most of its solar system abundance to the r-process. The changing ratio of these elements in stars over a wide metallicity range traces the changing contributions of these two processes to the Galactic abundance mix. Large s-process abundances can be the result of mass transfer from very evolved stars, so to identify these cases, we also report carbon abundances in our metal-poor stars. Results indicate that the s-process may be active as early as [Fe/H]=-2.6, alalthough we also find that some stars as metal-rich as [Fe/H]=-1 show no strong indication of s-process enrichment. There is a significant spread in the level of s-process enrichment even at solar metallicity.Comment: 64 pages, 15 figures; ApJ 2004 in pres

Differential Brain Activation to Angry Faces by Elite Warfighters: Neural Processing Evidence for Enhanced Threat Detection

10.1371/journal.pone.0010096PLoS ONE54