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M Cobb

Publications and source records attributed to M Cobb.

At least 37 records · Page 2Linked to original sources
PubMed1996

World-wide variation in Drosophila melanogaster sex pheromone: behavioural effects, genetic bases and potential evolutionary consequences.

In Drosophila melanogaster, male wing vibration, a key element of courtship behaviour, is most efficiently induced by a female-specific contact pheromone cis, cis 7,11 heptacosadiene (7,11 HD), which is the main mature female cuticular hydrocarbon in the CS laboratory strain. A study of 63 strains from around the world revealed that flies from Sub-Saharan Africa and the Caribbean are unique in showing low levels 7,11 HD and high levels of the position isomer 5,9 HD. This difference maps to chromosome III, perhaps indicating a simple genetic control of the 7,11 HD:5,9 HD ratio. Females from strains with high levels of 7,11 HD showed higher levels of mating and mated more rapidly than females with low levels of 7,11 HD. The results are discussed in light of recent discoveries of genetic differences between D. melanogaster strains from Africa and those from elsewhere around the world.

Animals↗
PubMed1996

Genotypic and phenotypic characterization of the Drosophila melanogaster olfactory mutation Indifferent.

Two Drosophila melanogaster third chromosomes carrying the EMS-induced mutations IndifferentA (IndfA) and IndifferentB (IndfB), previously isolated from larvae showing an anosmia when stimulated with nonanol, were recombined with a multi-marked chromosome in order to localize the mutant character(s). Recombinant strains were tested for their larval olfactory responses and classed as either mutant or wild type; both Indf characters were found to be located on the right arm of the chromosome, between ebony and claret. Deletion mapping suggests that the Indifferent wild-type character is a haplo-insufficiency and that IndfA and IndfB are located in cytological region 96A2-7. Deficiencies and both mutant strains were tested with 14 closely related odors (alcohols, acetates, acids and methyl esters, between eight and 10 carbons long). When stimulated with methyl octanoate, IndfA and IndfB appeared recessive; noncomplementation was observed for this phenotype in IndfA/IndfB hybrids indicating that the two characters are allelic. The overall responses of IndfA, IndfB and the deficiencies indicate that Indf is involved in processing organic odors of between eight and 10 carbons in length.

Animals↗
PubMed1994

Multiple genetic control of acetate-induced olfactory responses in Drosophila melanogaster larvae.

Behavioural responses of Drosophila melanogaster larvae were measured in response to olfactory stimulation with an homologous series of eight aliphatic n-acetates (methyl ... octyl acetate) and with cis-vaccenyl acetate. Larvae tended to be attracted to short-chain acetates (methyl ... pentyl) and repelled by longer chain acetates (hexyl, heptyl and octyl acetate). All larvae were strongly attracted to propyl acetate, irrespective of the dose studied. Larval olfactory responses generally declined with age. Two geographical strains showed specific anosmias. Katsunuma (Japan) larvae showed no response to hexyl acetate; chromosome substitution showed this behaviour to be controlled by genes on chromosome II. Tai (Ivory Coast) larvae showed no response to pentyl acetate; chromosome substitution showed that two genetic factors were primarily involved, on the X chromosome and chromosome III. The response was modulated by chromosome II. No effect of the Y chromosome was found. Two olfactory mutants were studied, olfC (X chromosome) and Indf (chromosome III); both mutants showed abnormal responses to certain acetates. The results are discussed in terms of various models of olfactory processing and the implications of these models for the number of genes involved in olfaction.

Acetates↗
PubMed1994

c-Jun N-terminal phosphorylation correlates with activation of the JNK subgroup but not the ERK subgroup of mitogen-activated protein kinases.

c-Jun transcriptional activity is stimulated by phosphorylation at two N-terminal sites: Ser-63 and -73. Phosphorylation of these sites is enhanced in response to a variety of extracellular stimuli, including growth factors, cytokines, and UV irradiation. New members of the mitogen-activated protein (MAP) kinase group of signal-transducing enzymes, termed JNKs, bind to the activation domain of c-Jun and specifically phosphorylate these sites. However, the N-terminal sites of c-Jun were also suggested to be phosphorylated by two other MAP kinases, ERK1 and ERK2. Despite these reports, we find that unlike the JNKs, ERK1 and ERK2 do not phosphorylate the N-terminal sites of c-Jun in vitro; instead they phosphorylate an inhibitory C-terminal site. Furthermore, the phosphorylation of c-Jun in vivo at the N-terminal sites correlates with activation of the JNKs but not the ERKs. The ERKs are probably involved in the induction of c-fos expression and thereby contribute to the stimulation of AP-1 activity. Our study suggests that two different branches of the MAP kinase group are involved in the stimulation of AP-1 activity through two different mechanisms.

Animals↗
PubMed1993

The interaction of SV40 small tumor antigen with protein phosphatase 2A stimulates the map kinase pathway and induces cell proliferation.

Interaction with SV40 small tumor antigen (small t) compromised the ability of multimeric protein phosphatase 2A to inactivate the mitogen-activated protein kinase ERK1 and the mitogen-activated protein kinase kinase MEK1. Transient expression of small t in CV-1 cells activated MEK and ERK but did not affect Raf activity. Small t stimulated the growth of quiescent CV-1 cells almost as effectively as did serum. Coexpression of kinase-deficient ERK2 blocked most, but not all, of the proliferation caused by small t. Activation of the mitogen-activated protein kinase pathway and stimulation of cell growth were dependent on the interaction of small t with protein phosphatase 2A. These findings indicate that SV40 small t is capable of inducing cell growth through blockade of protein phosphatase and deregulation of the mitogen-activated protein kinase cascade.

Animals↗
PubMed1993

Gender differences in lipoprotein responses to diet.

Gender and dietary saturated fat remain two strong predictors of coronary heart disease susceptibility. In a retrospective meta-analysis of five studies, we analyzed the impact of gender and diet composition on lipoprotein change, or 'response' (delta) in 63 normolipidemic subjects fed two contrasting, metabolically controlled diets. One diet had a low polyunsaturated to saturated fatty acid ratio (low P:S) and the second, a high P:S ratio in a crossover design. Lipid profile 'responsiveness' was calculated as the adjusted difference (mg/dl) following each diet period. Multivariate analysis of variance revealed that triglyceride (delta TG), very low density (delta VLDL-C), and high density lipoprotein cholesterol responses (delta HDL-C) were the only statistically significant, gender-specific lipid responders. Difference in low density lipoprotein (LDL-C) response to diet was similar between the sexes. Multiple regression analysis identified the independent predictors of delta HDL-C for males and females. In females, the HDL-C lowering was predicted by the percentage increase in polyunsaturated fatty acids, baseline HDL-C levels and, inversely by delta TG. The male predictor of delta HDL-C was diet alone (replacement of saturated fat by dietary polyunsaturated fatty acids). Results showed that while normolipidemic males and females show similar reductions in LDL-C following dietary change, delta HDL-C is gender-specific, with females showing a greater fall in the potentially 'beneficial' HDL-C than males. We conclude that a diet crossover may be of less benefit to normolipidemic females than to males, due to HDL-C lowering. Gender and diet may both become pivotal considerations in achieving plasma lipid goals.

Adolescent↗
PubMed1992

Genetic and developmental factors in the olfactory response of Drosophila melanogaster larvae to alcohols.

Olfactory responses of Drosophila melanogaster larvae to a homologous series of primary alcohols (methanol ... decanol) were tested. Alcohols at either extreme of the chain lengths studied (methanol, ethanol and decanol) evoked no significant responses. Heptanol and nonanol both produced dose-independent responses, larvae being attracted to heptanol and repulsed by nonanol. The remaining alcohols elicited dose-related attractive responses. Responses to hexanol and nonanol decline with increasing larval age. Genetic differences were found for the response to heptanol, with larvae from a Japanese strain, Katsunuma, being indifferent to this substance. Chromosome exchange revealed that a major factor involved in the response to heptanol is located on chromosome II; factors on chromosome III quantitatively modulate this response. Three mutant strains were isolated following EMS mutagenesis of chromosome III. These three strains, IndifferentA, IndifferentB and IndifferentC, show incomplete or total anosmia when stimulated with nonanol. Adult flies from these strains show similar effects. IndifferenB and C strains are dominant over the Canton-S control strain; the IndifferentA strain shows semi-dominance. Results are discussed in the light of the ecology of Drosophila larvae and the relation between olfactory stimulus and receptor conformation and number.

Alcohols↗
PubMed1992

c-Kit-kinase induces a cascade of protein tyrosine phosphorylation in normal human melanocytes in response to mast cell growth factor and stimulates mitogen-activated protein kinase but is down-regulated in melanomas.

The proto-oncogene c-Kit, a transmembrane receptor tyrosine kinase, is an important regulator of cell growth whose constitutively active oncogenic counterpart, v-kit, induces sarcomas in cats. Mutations in murine c-kit that reduce the receptor tyrosine kinase activity cause deficiencies in the migration and proliferation of melanoblasts, hematopoietic stem cells, and primordial germ cells. We therefore investigated whether c-Kit regulates normal human melanocyte proliferation and plays a role in melanomas. We show that normal human melanocytes respond to mast cell growth factor (MGF), the Kit-ligand that stimulates phosphorylation of tyrosyl residues in c-Kit and induces sequential phosphorylation of tyrosyl residues in several other proteins. One of the phosphorylated intermediates in the signal transduction pathway was identified as an early response kinase (mitogen-activated protein [MAP] kinase). Dephosphorylation of a prominent 180-kDa protein suggests that MGF also activates a phosphotyrosine phosphatase. In contrast, MGF did not induce proliferation, the cascade of protein phosphorylations, or MAP kinase activation in the majority of cells cultured from primary nodular and metastatic melanomas that grow independently of exogenous factors. In the five out of eight human melanoma lines expressing c-kit mRNAs, c-Kit was not constitutively activated. Therefore, although c-Kit-kinase is a potent growth regulator of normal human melanocytes, its activity is not positively associated with malignant transformation.

Cells, Cultured↗
PubMed1992

Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells.

The proto-oncogene c-MET encodes a transmembrane tyrosine kinase receptor for hepatocyte growth factor/scatter factor (HGF/SF). HGF/SF stimulates the proliferation and motility of various cell types. Because HGF/SF is also a melanocyte mitogen, we investigated the biological role of HGF/SF, including c-Met expression, activation and signal transduction, in normal and malignant human melanocytes. We show that HGF/SF is mitogenic in the presence of synergistic factors, such as basic fibroblast growth factor (bFGF) and mast cell growth factor (MGF) and that, by itself, it stimulates the motility of normal human melanocytes. The ligand also maintained high levels of tyrosinase activity and melanin content in theses cells. Signal transduction by HGF/SF included phosphorylation of tyrosyl residues on c-Met, a cascade of tyrosine phosphorylations on several other proteins and activation of microtubule-associated protein kinase/extracellular signal-regulated kinase. Met expression and activity are normal in human melanomas, and constitutive activity of HGF/SF in retrovirally infected autonomously proliferative mouse melanocytes is insufficient to confer the malignant phenotype. Our findings suggest that activation of Met in response to HGF/SF may contribute to malignant progression synergistically with the aberrant expression of bFGF in malignant melanocytes and that, in addition, the peptide may promote dispersion of factor-dependent melanocytes from early stages of primary melanomas to ectopic sites.

Animals↗
PubMed1991

Regulation of cholesterol biosynthesis in sitosterolemia: effects of lovastatin, cholestyramine, and dietary sterol restriction.

We investigated the effects of lovastatin, cholestyramine, and dietary sterol restriction on cholesterol synthesis and low density lipoprotein receptor function in freshly isolated mononuclear leukocytes from two unrelated sitosterolemic families. Total plasma sterol concentrations were elevated in the two homozygous sitosterolemic subjects (343 and 301 vs. 185 mg/dl in controls) and contained increased amounts of plant sterols and 5 alpha-saturated stanols (20% and 8% vs. less than 1% in controls), but were not significantly different from controls in the two heterozygous subjects. The rates of conversion of acetate to cholesterol by mononuclear leukocytes were subnormal in all homozygous and heterozygous subjects and correlated with markedly reduced microsomal 3-hydroxy-3-methylglutaryl co-enzyme A (HMG-CoA) reductase activity. In the two homozygous subjects, cholestyramine treatment decreased plasma sterols 29% and 35%, and yet was associated with a paradoxical decline in mononuclear leukocyte HMG-CoA reductase activity. In contrast, plasma sterol concentrations decreased 14% and 5%, and mononuclear leukocyte HMG-CoA reductase activities increased 13% and 46% in three control and one heterozygous subjects treated with cholestyramine, respectively. Plasma sterol concentrations in the homozygous subjects unexpectedly failed to decline during treatment with lovastatin or a low sterol diet. In distinction, plasma sterol concentrations in three control and one heterozygous subjects dropped 28% and 31%, respectively, during treatment with lovastatin. Both cholestyramine and low dietary sterols stimulated low density lipoprotein receptor function. These results demonstrate a marked abnormality in cholesterol homeostasis in patients with homozygous sitosterolemia with xanthomatosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Antenatal spontaneous perforation of the extrahepatic biliary tree.

Spontaneous perforation of the biliary system is an unusual neonatal phenomenon that is rarely recognized at birth. To date, it has not been reported antenatally. A 16-year-old pregnant adolescent had an ultrasonogram at 25 weeks of pregnancy that revealed ascites in the fetus. After the infant was delivered at 32 weeks, a hepato-iminodiacetic acid scan showed a spontaneous rupture of the common bile duct. The infant was treated with external drainage of the biliary tree and recovered well. This case demonstrates that spontaneous perforations of the bile ducts can occur much earlier than the usually described 2 to 12 weeks after birth, can be diagnosed antenatally, and should be added to the list of causes of fetal ascites.

Adolescent↗
PubMed1989

Oleic acid lung injury increases plasma prostaglandin levels.

To determine whether lung injury causes increased plasma prostaglandin (PG) levels, 35 rabbits received oleic acid and 35 served as controls. Half of each group also received 4 ml/kg of Intralipid over one hour and at least five in each subgroup received indomethacin 7.5 mg/kg. Arterial and venous plasma concentrations of PGE2, 6-keto-PGF1 alpha, and PGF2 alpha-M were measured. Venous PGE2 was significantly higher in the oleic acid-injured than in the normal lung group, 1560 +/- 270 (Mean +/- SEM) versus 880 +/- 140 pg/ml (p less than .05). Plasma levels were reduced by 50% with indomethacin, but PGE2 levels remained significantly higher than in the normal lung group, 850 +/- 180 versus 480 +/- 60 for arterial (p less than .05) and 820 +/- 140 versus 480 +/- 80 for venous (p less than .05), respectively. PGF2 alpha-M levels were significantly higher in the lung injury group, 240 +/- 50 versus 50 +/- 40 pg/ml for arterial (p less than .05) and 220 +/- 50 versus 95 +/- 40 for venous (p less than .05), respectively. These lung injury-related increases in PGE2 and PGF2 alpha-M appear related both to increased pulmonary production and to decreased pulmonary clearance. With Intralipid infusion, however, arterial PGE2 increased by 500 +/- 260 pg/ml compared to baseline (p less than .05) with no change in venous PGE2, indicating in this instance that the increase in arterial PGE2 levels is related to increased pulmonary production.

Animals↗
PubMed1989

Patient-side immunoassay system with a single-use cartridge for measuring analytes in blood.

We describe an immunoassay system suited to patient-side assay of therapeutic drugs and blood proteins. The system consists of an electronic monitor and single-use plastic cartridges containing dry reagents and liquid diluents. The monitor is turned on by insertion of a cartridge. To run the test, the user applies an unmeasured drop of blood to the cartridge when prompted by the monitor. All subsequent steps are performed without further user intervention and results are provided in less than 3 min. The system hemolyzes and precisely dilutes the blood. Hemoglobin concentration is measured, then the diluted blood is precisely diluted further and mixed with two dry reagents. The drug concentration is measured by a turbidimetric latex agglutination inhibition reaction. Theophylline and hemoglobin assay results for clinical samples correlate well with results of widely used comparison methods.

Hemoglobins↗