Role of brain insulin receptor in control of body weight and reproduction

Insulin receptors (IRs) and insulin signaling proteins are widely distributed throughout the central nervous system (CNS). To study the physiological role of insulin signaling in the brain, we created mice with a neuron-specific disruption of the IR gene (NIRKO mice). Inactivation of the IR had no impact on brain development or neuronal survival. However, female NIRKO mice showed increased food intake, and both male and female mice developed diet-sensitive obesity with increases in body fat and plasma leptin levels, mild insulin resistance, elevated plasma insulin levels, and hypertriglyceridemia. NIRKO mice also exhibited impaired spermatogenesis and ovarian follicle maturation because of hypothalamic dysregulation of luteinizing hormone. Thus, IR signaling in the CNS plays an important role in regulation of energy disposal, fuel metabolism, and reproduction.     

Microbiology. Turning up the heat on Histoplasma capsulatum

Many fungal pathogens are opportunistic, that is, they infect individuals who have a compromised immune system. Histoplasma capsulatum is a common pathogenic fungus that lives happily inside the phagosomes of macrophages. As Klein explains in his Perspective, an important H. capsulatum virulence factor, CBP1, has been found, which mops up free calcium ions within the phagosome, enabling the yeast to live under calcium-poor conditions (Sebhgati et al.). Chelating calcium ions may also have the added benefit that when the phagosome fuses with the lysosome, destructive lysosomal enzymes that require calcium ions for activity remain inactive.     

Contributions of two types of calcium channels to synaptic transmission and plasticity

In Aplysia sensory and motor neurons in culture, the contributions of the major classes of calcium current can be selectively examined while transmitter release and its modulation are examined. A slowly inactivating, dihydropyridine-sensitive calcium current does not contribute either to normal synaptic transmission or to any of three different forms of plasticity: presynaptic inhibition, homosynaptic depression, and presynaptic facilitation. This current does contribute, however, to a fourth form of plasticity--modulation of transmitter release by tonic depolarization of the sensory neuron. By contrast, a second calcium current, which is rapidly inactivating and dihydropyridine-insensitive, contributes to release elicited by the transient depolarization of an action potential and to the other three forms of plasticity.     

A novel mechanism of somatic rearrangement predicted by a human T-cell antigen receptor beta-chain complementary DNA

The T-cell antigen receptor is a cell surface molecule vital in mediating the cellular immune response. The arrangement and rearrangement of the gene segments encoding the beta-chain polypeptide of the receptor are similar to those of immunoglobulin gene segments. The two constant region genes of the human T-cell antigen receptor are 8 kilobases apart with a cluster of joining segments located 5' of each constant region gene. Although most beta-chain gene rearrangements involve the variable, diversity, and joining segments, analysis of a beta-chain complementary DNA clone suggests the occasional occurrence of another type of rearrangement.     

Sampling and characterization of air for organic compounds

Computerized gas chromatography/mass spectrometry was applied to the analysis of organic compounds in air at a National Air Surveillance Network station in Kansas City. Sampling approaches used included particulate sampling, adsorption on XAD-2 resin followed by solvent elution, and adsorption on Tenax GC followed by direct desorption onto a gas chromatography column. Eighty-two compounds were identified. Unusually large amounts of phenol and phenolformaldehyde resin intermediates were found.     

Metabolism of naturally occurring [13C]glucose given orally to horses

In 5 horses, 13CO2/12CO2 ratios in expired air were determined using isotope mass spectroscopy to investigate metabolism of naturally occurring [13C]glucose. Oral glucose tolerance tests (OGTT) were performed using maize or beet glucose. Maize has a higher 13C concentration than that of most plants. The 13CO2/12CO2 ratios after OGTT was performed using maize glucose were compared with 13CO2/12CO2 ratios in expired air after OGTT was performed using beet glucose. The ratio also was determined during the period horses were not fed. Using OGTT, all horses were glucose tolerant. The OGTT performed using beet glucose led to minimal changes in 13CO2/12CO2 ratios. The 13CO2/12CO2 ratios decreased significantly (P less than 0.01) when horses were not fed. After oral dosing with maize glucose, 13CO2/12CO2 ratios reached maximal increases 5 hours after dosing and reached baseline values 15 hours after dosing.     

Histamine inhalation provocation test: method to identify nonspecific airway reactivity in equids

After inhalation of increased concentrations of histamine solutions, equids had a decrease in dynamic compliance (Cdyn) and an increase in airway resistance, work of breathing, and maximum intrathoracic differences in pressure. Because the change in Cdyn correlated best with the inhaled histamine concentrations, airway reactivity was assessed by the decrease in Cdyn. With the use of linear regression, histamine concentrations were calculated; this resulted in a 35% reduction of Cdyn and these concentrations were defined as 35% provoking concentration Cdyn. The histamine inhalation provocation test was carried out in 40 equids. Nonspecific airway hyperreactivity was not present in equids that did not have clinical signs of respiratory tract disease, but it was present in 25% of the equids with low-grade lung disease and in all equids with severe lung disease.