Somatostatin: a historical perspective

Following the discovery and biochemical characterization of natural somatostatin its action profile has been thoroughly investigated. Although the name somatostatin was coined in virtue of its growth hormone release-inhibiting properties, a number of central and peripheral endocrine and paracrine actions have been ascribed to this peptide. Its inhibitory effect on a series of pituitary and gastrointestinal hormones has characterized somatostatin as a classical brain-gut hormone. Circulating and tissue levels of somatostatin and its possible physiological role are analyzed and clinical implications are drawn.     

Firefly luminescence: a historical perspective and recent developments.

Significant advances have occurred regarding our knowledge of firefly luciferase mechanisms. Although most of this progress was an outcome of molecular biology and structural studies, important achievements have also occurred on its fundamental chemistry. Those developments are here summarized and presented in a historical perspective.     

BioMetals: a historical and personal perspective

Understanding of BioMetals developed basically from a starting point about 60 years ago to current mechanistic understanding of the biological behavior of many metal ions from protein structural and functional studies. Figure 1 shows a Biochemical Periodic Table, element by element, with requirements, roles and biochemistry of the specific ions indicated. With few exceptions, the biology is of the ions formed and not of the elemental state of each. Early BioMetals efforts defined nutritional growth needs for animals, plants and microbes for inorganic “macro-nutrients” such as magnesium, calcium, potassium, sodium, and phosphate and of “micronutrients” such as copper, iron, manganese and zinc. Surprises came early with regard to microbes, for example the finding that Escherichia coli (then and now the standard microbial model) grows happily in the apparent total absence of calcium, sodium, and chloride, which are certainly major animal nutrients. Some elements such as mercury and arsenic are never required by living cells, but are always toxic, often at very low levels. Therefore, the division into nutrient elements and toxic elements came soon. For most inorganic nutrients, excessive amounts can be toxic as well, for example for copper and iron.     

Intermediate filaments: a historical perspective

Intracellular protein filaments intermediate in size between actin microfilaments and microtubules are composed of a surprising variety of tissue specific proteins commonly interconnected with other filamentous systems for mechanical stability and decorated by a variety of proteins that provide specialized functions. The sequence conservation of the coiled-coil, alpha-helical structure responsible for polymerization into individual 10 nm filaments defines the classification of intermediate filament proteins into a large gene family. Individual filaments further assemble into bundles and branched cytoskeletons visible in the light microscope. However, it is the diversity of the variable terminal domains that likely contributes most to different functions. The search for the functions of intermediate filament proteins has led to discoveries of roles in diseases of the skin, heart, muscle, liver, brain, adipose tissues and even premature aging. The diversity of uses of intermediate filaments as structural elements and scaffolds for organizing the distribution of decorating molecules contrasts with other cytoskeletal elements. This review is an attempt to provide some recollection of how such a diverse field emerged and changed over about 30 years.     

The Tinel sign: a historical perspective

The Tinel sign is one of the most well-known and widely used clinical diagnostic tools in medicine. Aside from Jules Tinel, after whom the sign is named, several authors have described the famous "tingling" sign seen in regenerating injured nerves. In fact, Tinel was not the first to present the sign to the scientific community. The clinical value and utility of the Tinel sign have remained in question since its introduction; many may misinterpret the sign as a prelude to complete functional recovery of injured nerves, when in fact it only signals the progress of nerve regeneration. Today the Tinel sign is widely associated with the diagnosis of carpal tunnel syndrome and in the evaluation of regenerating peripherally injured nerves. Knowledge of the history and misconceptions surrounding the sign provides clinicians today with a greater appreciation of current debates on the use of the Tinel sign.     

Exercise training improves muscle insulin resistance but not insulin receptor signaling in obese Zucker rats.

Exercise training improves skeletal muscle insulin sensitivity in the obese Zucker rat. The purpose of this study was to investigate whether the improvement in insulin action in response to exercise training is associated with enhanced insulin receptor signaling. Obese Zucker rats were trained for 7 wk and studied by using the hindlimb-perfusion technique 24 h, 96 h, or 7 days after their last exercise training bout. Insulin-stimulated glucose uptake (traced with 2-deoxyglucose) was significantly reduced in untrained obese Zucker rats compared with lean controls (2.2 +/- 0.17 vs. 5.4 +/- 0.46 micromol x g(-1) x h(-1)). Glucose uptake was normalized 24 h after the last exercise bout (4.9 +/- 0.41 micromol x g(-1) x h(-1)) and remained significantly elevated above the untrained obese Zucker rats for 7 days. However, exercise training did not increase insulin receptor or insulin receptor substrate-1 (IRS-1) tyrosine phosphorylation, phosphatidylinositol 3-kinase (PI3-kinase) activity associated with IRS-1 or tyrosine phosphorylated immunoprecipitates, or Akt serine phosphorylation. These results are consistent with the hypothesis that, in obese Zucker rats, adaptations occur during training that lead to improved insulin-stimulated muscle glucose uptake without affecting insulin receptor signaling through the PI3-kinase pathway.     

Overview: hepatocytes and cryopreservation--a personal historical perspective.

Hepatocytes represent an important tool for the investigation of species differences in drug metabolism and toxicity. Data obtained with hepatocytes from multiple animal species, including man, allow better prediction of the effects of xenobiotics in man. Cryopreservation of hepatocytes extends the use of this important experimental system by enhancing the convenience of its use. Also, it allows the researchers to perform experiments not plausible with freshly isolated hepatocytes, such as the direct comparison of xenobiotic toxicity and metabolism in hepatocytes from multiple human donors in a single experiment.     

Type III restriction-modification enzymes: a historical perspective

Restriction endonucleases interact with DNA at specific sites leading to cleavage of DNA. Bacterial DNA is protected from restriction endonuclease cleavage by modifying the DNA using a DNA methyltransferase. Based on their molecular structure, sequence recognition, cleavage position and cofactor requirements, restriction–modification (R–M) systems are classified into four groups. Type III R–M enzymes need to interact with two separate unmethylated DNA sequences in inversely repeated head-to-head orientations for efficient cleavage to occur at a defined location (25–27 bp downstream of one of the recognition sites). Like the Type I R–M enzymes, Type III R–M enzymes possess a sequence-specific ATPase activity for DNA cleavage. ATP hydrolysis is required for the long-distance communication between the sites before cleavage. Different models, based on 1D diffusion and/or 3D-DNA looping, exist to explain how the long-distance interaction between the two recognition sites takes place. Type III R–M systems are found in most sequenced bacteria. Genome sequencing of many pathogenic bacteria also shows the presence of a number of phase-variable Type III R–M systems, which play a role in virulence. A growing number of these enzymes are being subjected to biochemical and genetic studies, which, when combined with ongoing structural analyses, promise to provide details for mechanisms of DNA recognition and catalysis.     

Great Salt Lake microbiology: a historical perspective

Over geologic time, the water in the Bonneville basin has risen and  fallen, most dramatically as freshwater Lake Bonneville lost enormous volume 15,000–13,000 years ago and became the modern day Great Salt Lake. It is likely that paleo-humans lived along the shores of this body of water as it shrunk to the present margins, and native peoples inhabited the surrounding desert and wetlands in recent times. Nineteenth century Euro-American explorers and pioneers described the geology, geography, and flora and fauna of Great Salt Lake, but their work attracted white settlers to Utah, who changed the lake immeasurably. Human intervention in the 1950s created two large sub-ecosystems, bisected by a railroad causeway. The north arm approaches ten times the salinity of sea water, while the south arm salinity is a meager four times that of the oceans. Great Salt Lake was historically referred to as sterile, leading to the nickname “America’s Dead Sea.” However, the salty brine is teaming with life, even in the hypersaline north arm. In fact, scientists have known that this lake contains a diversity of microscopic lifeforms for more than 100 years. This essay will explore the stories of the people who observed and researched the salty microbiology of Great Salt Lake, whose discoveries demonstrated the presence of bacteria, archaea, algae, and protozoa that thrive in this lake. These scientists documented the lake’s microbiology as the lake changed, with input from human waste and the creation of impounded areas. Modern work on the microbiology of Great Salt Lake has added molecular approaches and illuminated the community structures in various regions, and fungi and viruses have now been described. The exploration of Great Salt Lake by scientists describing these tiny inhabitants of the brine illuminate the larger terminal lake with its many facets, anthropomorphic challenges, and ever-changing shorelines.     

Laticifers: An historical perspective

This review describes the development of the laticifer concept, with emphasis upon the nonarticulated type, from early observations of plant exudates and “juices” to the presentation of laticifers by Esau (1953). Classical writers and herbalists described practical applications of these substances. With the advent of the microscope early investigators believed that these substances occurred in structures present in most, if not all, plants and, wrongly, equated these structures to the circulatory system in animals. Introduction of the term, latex, into botany derived from its early use as a term for a blood component by physicians, and not for analogy to milk. However, the origin of the terms, laticifer and laticiferous, remains uncertain. Initial studies of laticifers were marked by the controversy of whether they represented intercellular spaces or elongated cells. Confirmation of their cellular character led to the designation of nonarticulated and articulated laticifers. Nonarticulated laticifers were shown to arise during early embryogeny in some plants. The ontogenetic origin of the articulated laticifer was unclear to early workers, but new laticifers were detected to be formed by cambium activity. Nonarticulated laticifers were described to develop by intrusive growth whereby tips of the cell penetrated between adjacent cells. The coenocytic condition of the nonarticulated laticifer resulted from nuclear divisions along the cell positioned in the growth region of the shoot and the subsequent distribution of the daughter nuclei along the length of the cell.     

Reflexes from the lungs and airways: historical perspective.

Historical aspects of respiratory reflexes from the lungs and airways are reviewed, up until about 10 yr ago. For most of the 19th century, the possible reflex inputs into the "respiratory center," the position of which had been identified, were very speculative. There was little concept of reflex control of the pattern of breathing. Then, in 1868, Breuer published his paper on "The self-steering of respiration via the Nervus Vagus." For the first time this established the role of vagal inflation and deflation reflexes in determining the pattern of breathing. Head later extended Breuer's work, and Kratschmer laid a similar basis for reflexes from the nose and larynx. Then, 50-60 yr later, the development of the thermionic valve and the oscilloscope allowed recording action potentials from single nerve fibers in the vagus. In 1933, Adrian showed that slowly adapting pulmonary stretch receptors were responsible for the inflation reflex. Later, Knowlton and Larrabee described rapidly adapting receptors and showed that they mediated deep augmented breaths and the deflation reflex. Still later, it was established that rapidly adapting receptors were, at least in part, responsible for cough. In 1954, Paintal began his study of C-fiber receptors (J receptors), work greatly extended by the Coleridges. Since approximately 10 yr ago, when the field of this review stops, there has been an explosion of research on lung and airway receptors, many aspects of which are dealt with in other papers in this series.