Insulin receptors: Structure and function

Summary and conclusions The recent characterization of the human insulin receptor structure and its intrinsic tyrosine kinase activity represent major advances in our understanding of the mechanism of insulin action. It is reasonable to think that the insulin-induced autophosphorylation and activation of its receptor kinase represent an important event in the action of insulin on cell metabolism and growth. The fundamental research reviewed may be followed by the discovery of molecular receptor defects in clinical syndromes of insulin resistance.     

Hemoglobin causes both endothelium-dependent and endothelium-independent contraction of the pig coronary arteries, independently of an inhibition of EDRF effects

Hemoglobin is widely used as an inhibitor of EDRF effects. Hemoglobin contracts pig coronary arteries in vitro. However, during this contraction, effects of substance P and bradykinin which act via the EDRF are not inhibited. This means that the hemoglobin contraction is not caused by inhibition of the EDRF. This contraction is caused by a substance released from the endothelium, and by eicosano?ds released from the smooth muscles.     

Effect of aluminium phosphate gel on whole-body retention of simultaneously administered226Ra,85Sr and47Ca in mice

Résumé L'administration presque simultanée d'un gel de phosphate d'alumine et de²²⁶RaCl₂ réduit de 800 fois l'absorption intestinale du²²⁶Ra chez la souris. La charge corporelle en⁸⁵Sr et⁴⁷Ca est réduite d'environ 10 resp. 3 fois.     

Demographic and environmental relations of two rare Astragalus species endemic to Washington County, Utah: Astragalus holmgreniorum and A. ampullarioides

Two endemic locoweeds of Washington County, Utah, Astragalus holmgreniorum and A. ampullarioides , were recently listed as federally endangered plant species (Federal Register 2001). They both occur in few, small populations surrounded by increasing human activity in the St. George, Utah, area. Demographic and habitat studies have been ongoing since 1992 and results of those studies are presented here. Astragalus holmgreniorum (Holmgren locoweed) is presently limited to 1 larger population and 2 smaller, isolated populations on the eastern and western edges of its range. It is a short-lived perennial that grows primarily on the Virgin limestone member of the Moenkopi Formation. Density of A. holmgreniorum over the 10-year study averaged about 2 plants per m 2 . The number of living plants of this species perhaps never exceeds 10,000. In drought years A. holmgreniorum populations are as much as 95% smaller than in years with adequate water, and few plants produce flowers that successfully contribute to the seed bank. Astragalus ampullarioides (Shivwits locoweed) occurs in 4 populations where plant density fluctuated between 0.5 and 4.8 per m 2 during our study period (average = 2.6). This locoweed is restricted to clay soils of the Chinle Formation. Direct threats to both Astragalus species include widespread urbanization, road construction, population fragmentation, and off-highway vehicle use. Indirect threats include competition from aggressive, introduced annual species such as Bromus rubens, B. tectorum, Malcolmia africana , and Erodium cicutarium . Our data show that 3 of 4 species most closely associated with these Astragalus species are introduced. Studies of seed banks and reproduction biology, as well as continued monitoring of these Astragalus species, are critically needed. Studies of the consequences of competition from alien and native species on seedling establishment of these locoweeds are especially needed.     

Dynamics of a dwarf bear-poppy ( Arctomecon humilis ) population over a sixteen-year period

A population of the dwarf bear-poppy ( Arctomecon humilis Coville, Papaveraceae) at Red Bluff, Washington County, Utah, was monitored twice annually between 1987 and 2002. This is a narrowly endemic, gypsophilous species that has been formally listed as endangered since 1979. During the 16 years of observation, density of this species has fluctuated between 3 and 1336 individuals on the 0.07-ha monitoring plot. Moderate to large recruitments of seedlings occurred in 1992, 1995, and 2001. Seedling recruitments from a large, long-lived seed bank are triggered by abundant precipitation during the February-April period. At least 5.0 cm of rainfall is required during that interval to produce any seedlings. Seedlings experienced considerable mortality in the 1st few months of life in all observed cases. The average seedling initiated in the very large recruitment event of 1992 survived for only 2.6 years. Seedlings in that cohort that were alive 1 year after germination had an average longevity of 4.6 years. None of the seedlings that emerged in 1992 were still alive in October 2002. Mortality in this species was poorly correlated with fluctuations in precipitation or temperature. No epidemics of parasites or herbivores were observed. Mortality in the species appears to be caused by a variety of factors acting over a cohort's lifetime.     

Fall diet of blue grouse in Oregon

The early fall diet of Oregon blue grouse ( Dendragapus obscurus pallidus ) from Wallowa County, Oregon, was determined from 145 crops obtained during 1981 and 1982. Of more than 50 plant and animal foods in the diet, short-horned grasshoppers ( Acrididae ), prickly lettuce ( Lactuca serriola ), yellow salsify ( Tragopogon dubius ), wild buck-wheat ( Eriogonum spp.), and snowberry ( Symphoricarpos albus ) occurred in 30% or more of the crops and collectively amounted to 68% of the diet by weight. Seven of the 12 most common foods were consumed differentially by the four sex and age classes of birds. Results indicated that blue grouse foraged in forest and grassland habitats.     

Seasonal trends and colonization patterns of macroinvertebrate assemblages in two streams with contrasting flow regimes

Patterns of colonization by macroinvertebrates were examined in two streams that differ in flow regime: a snowmelt system and a mesic groundwater system. Experiments were conducted during spring runoff, summer baseflow, and winter baseflow using artificial substrata. Colonization patterns reflected seasonal changes in benthic macroinvertebrate assemblages and life histories in each stream. The density and biomass of benthic organisms were approximately 3X greater in winter than in either spring or summer for both streams. Similarly, colonization was greater in winter than in spring or summer for both streams. In spring, colonization patterns were different between streams, with colonization being imperceptible in the snowmelt stream. Macroinvertebrate abundance fluctuated during the summer colonization experiment at both sites, resulting from a complex interplay among population emergence, recruitment, and/or movement. Assemblages in the snowmelt system primarily comprised mobile or ruderal taxa, such as Beatis tricaudatus and Chironomidae, whereas relatively sessile taxa, such as Glossoma nigrior , were predominant in the mesic groundwater system. Seasonal patterns of colonization differed among stream types primarily because of the profound interplay of flow regime and temperature on benthic community structure and organism life history.     

The peripheral myelin protein gene PMP-22 is contained within the Charcot-Marie-Tooth disease type 1A duplication.

Charcot-Marie-Tooth disease (CMT1) is the most common form of inherited peripheral neuropathy. Although the disease is genetically heterogeneous, it has been demonstrated that the gene defect is the most frequent type (CMT1A) is the result of a partial duplication of band 17p11.2. Recent studies suggested that the peripheral hypomyelination syndrome in the trembler (Tr) mouse, a possible animal model for CMT1 disease, is associated with a point mutation in the peripheral myelin protein-22 gene (pmp-22). Expression of pmp-22 is particularly high in Schwann cells, and the protein is found in peripheral myelin. We now report that the human PMP-22 gene is contained within the CMT1A duplication. We therefore, suggest that increased dosage of the PMP-22 gene may be the cause of CMT1A neuropathy.     

Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus

We have recently described two kindreds presenting thoracic aortic aneurysm and/or aortic dissection (TAAD) and patent ductus arteriosus (PDA) and mapped the disease locus to 16p12.2-p13.13 (ref. 3). We now demonstrate that the disease is caused by mutations in the MYH11 gene affecting the C-terminal coiled-coil region of the smooth muscle myosin heavy chain, a specific contractile protein of smooth muscle cells (SMC). All individuals bearing the heterozygous mutations, even if asymptomatic, showed marked aortic stiffness. Examination of pathological aortas showed large areas of medial degeneration with very low SMC content. Abnormal immunological recognition of SM-MHC and the colocalization of wild-type and mutant rod proteins in SMC, in conjunction with differences in their coimmunoprecipitation capacities, strongly suggest a dominant-negative effect. Human MYH11 gene mutations provide the first example of a direct change in a specific SMC protein leading to an inherited arterial disease.     

Mutations in the gene encoding pejvakin, a newly identified protein of the afferent auditory pathway, cause DFNB59 auditory neuropathy

Auditory neuropathy is a particular type of hearing impairment in which neural transmission of the auditory signal is impaired, while cochlear outer hair cells remain functional. Here we report on DFNB59, a newly identified gene on chromosome 2q31.1-q31.3 mutated in four families segregating autosomal recessive auditory neuropathy. DFNB59 encodes pejvakin, a 352-residue protein. Pejvakin is a paralog of DFNA5, a protein of unknown function also involved in deafness. By immunohistofluorescence, pejvakin is detected in the cell bodies of neurons of the afferent auditory pathway. Furthermore, Dfnb59 knock-in mice, homozygous for the R183W variant identified in one DFNB59 family, show abnormal auditory brainstem responses indicative of neuronal dysfunction along the auditory pathway. Unlike previously described sensorineural deafness genes, all of which underlie cochlear cell pathologies, DFNB59 is the first human gene implicated in nonsyndromic deafness due to a neuronal defect.