Carmichael, Stephen W.

Abstract Temporal resolution has long been a challenge to microscopists. Certainly, spatial resolution has occupied center stage, but we're all concerned about what happens over time in a biologic system, for example, a cell. Tags such as green fluorescent protein (GFP) have been used with confocal microscopy and other light microscopic techniques to achieve outstanding temporal resolution, but good spatial and temporal resolution have proven to be difficult to achieve simultaneously. This has been accomplished in a remarkable study by Guido Gaietta, Thomas Deerinck, Stephen Adams, James Bouwer, Oded Tour, Dale Laird, Gina Sosinsky, Roger Tsien, and Mark Ellisman, who demonstrated a pulse-chase technique that correlates with both fluorescence and electron microscopy.

Abstract The atomic force microscope (AFM) is well known for its outstanding spatial resolution, but it is becoming increasingly useful as the instrument for force spectroscopy. In the force spectroscopy mode, the AFM can measure tiny tension forces, in the piconewton (pN) range. Daniel Müller, Wolfgang Baurmeister, and Andreas Engel have used the AFM in both the imaging and force spectroscopy modes to pull proteins out of membranes in a controlled fashion. Müller et al. used Deinococcus radiodurans, a bacterium best known for its high resistance to radiation (as its Genus name implies), as their test subject. They extracted a highly regular membrane from the bacterium, the hexagonally packed intermediate (HPl) layer. They mounted the HPI on mica, so that the hydrophilic outer surface of the HPI adsorbed strongly to the mica, exposing the hydrophobic inner surface to the silicon nitride AFM stylus.

Abstract The code for the human genome is essentially complete, opening an expansive book about our biologic composition. But the problem is to read this book. The font size is very small, What you are reading now is 9 point font, and genetic information would correspond to approximately 10-50 point font, six orders of magnitude smaller. There are methods to derive genetic information, but recently Adam Woolley, Chantal Guillemette, Chin-Li Cheung, David Housman, and Charles Lieber have developed an elegant way to directly read genetic information with a microscope. The microscope they used was an atomic force microscope (AFM) that employed a single-walled carbon nanotube as its probe.

Abstract We are all familiar with the 4 groups of human blood types; 0, A, B, and AB. Each group is characterized by specific molecules on the surface of the red blood cells (RBCs). Recently, Michel Grandbois, Wolfgang Dettmann, Martin Benoit, and Hermann Gaub have modified the atomic force microscope (AFM) to use the different affinities of these molecules to produce an image. A key step was to specifically functionalize the scanning probe tip of the AFM. What this means is to covalently attach an active molecule to the tip. The active molecule they used was a Iectin derived from the snail Helix pomatia (this is the same snail valued by the French as escargot). This Iectin binds specifically to molecules found on the surface of RBCs in blood group A (N-acetylgalactosamine-terminated glycolipids), but these molecules are not found in blood group O. But if the Iectin was bound directly to the AFM tip, nonspecific adsorption to the specimens would occur.

Abstract Regulated secretion occurs when the ceil detects a signal, vesicles containing the secretory product fuse with the plasma membrane of the cell, and the contents are released into the extracellular space. This mechanism is called exocytosis. Many laboratories around the world have studied exocytosis for the past couple of decades, and we know a lot about the many steps that are involved. The cytoskeleton appears to play a role in allowing vesicles to approach the plasma membrane, and many other proteins are in the cascade between reception of the signal and the release of the secretory products.

Abstract The compound light microscope has been used by patholo gists for centuries, and remains the common tool for making a diagnosis. A half century ago, the electron microscope (EM) was introduced, and has aiso been proven to be a valuable, but expensive, tool. In the meantime, other tools and methods have worked their way into the pathologists’ armamentarium, with immunohistochemical, genetic, and molecular techniques being the most obvious examples. Josep Lloreta-Truil, Lola Ferrer, Teresa Ribalta, Marco Pavesi, and Sergio Serrano examined the literature to determine the frequency and appropriateness with which pathologists use the EM in their studies.

Hilton's Law, put forth 150 years ago, is well known and frequently taught in anatomy courses. We critically analyzed the complex description of associated muscular, cutaneous, and articular innervations in order to assess the general applicability of Hilton's Law. We applied rules for interpretation of the Law extrapolated upon but based on Hilton's original writings, and excluded obscure supplementary clauses not considered as part of the Law. We found the Law, as originally written and as we interpreted with some latitude, to be reliable and applicable to all cranial and peripheral nerves. Hilton's Law is a powerful springboard to understand articular anatomy and pathophysiology. Clin. Anat. 548–555, 2014. © 2013 Wiley Periodicals, Inc.