Genomic structure of the human ezrin gene

The ERM proteins, ezrin, radixin, and moesin, act as linkers between the plasma membrane and actin cytoskeleton. They are involved in a variety of cellular functions, such as cell adhesion, migration, and the organization of cell surface structures, and are highly homologous, both in protein sequence and in functional activity, with merlin/schwannomin, a neurofibromatosis-2-associated tumor-suppressor protein. We report here the genomic structure and intron junction sequences of the human ezrin gene. Ezrin consists of 13 exons and spans approximately 24 kb genomic DNA. The coding parts of the exons range in size from 12 bp to 275 bp and the introns from 182 bp to 7 kb. The genomic structures of ezrin and moesin are highly conserved, suggesting their recent divergence. Radiation hybrid mapping has refined the location of ezrin to the interval between D6S442 and D6S281. Received: 1 June 1998 / Accepted: 25 August 1998     

Is Leptin Concentration Associated with the Insulin Resistance Syndrome in Nondiabetic Men?

HAFFNER, STEVEN M., LEENA MYKKÄNEN, DAVID L. RAINWATER, PAULI KARHAPÄÄ, AND MARKU LAAKSO. Is leptin concentration associated with the insulin resistance syndrome in nondiabetic men? Obes Res. Objective Insulin resistance has been strongly associated with cardiovascular risk. Recently, leptin, a hormone that regulates appetite, has been associated with both obesity and insulin resistance. However, the possible relation of leptin to the insulin resistance syndrome has been controversial. Research Methods and Procedures To explore this issue, we examined the relation of leptin to blood pressure, lipid levels, low density lipoprotein (LDL) size, and glucose levels in 87 normoglycemic men. Results Leptin levels were significantly correlated with body mass index (BMI) (r = 0.494), fasting insulin (r = 0.576), whole-body glucose disposal rate (GDR) (r = ?0.566), fasting glucose (r = 0.510), total triglycerides (r= 0.294), apolipoprotein B 0 = 0.223), systolic blood pressure (r= O.223), and LDL size (r = ?0.244). After adjustment for BMI and GDR, leptin levels remained significantly correlated with fasting insulin, fasting glucose, triglyceride, apolipoprotein B, and systolic blood pressure. Leptin levels were also correlated with the number of metabolic risk factors (dyslipidemia, systolic blood pressure, and fasting glucose). Discussion We conclude that leptin concentrations may be associated with several cardiovascular risk factors related to insulin resistance syndrome. These associations are only partly explained by leptin's relationship with BMI and GDR.     

Hexokinase II-deficient mice. Prenatal death of homozygotes without disturbances in glucose tolerance in heterozygotes.

Type 2 diabetes is characterized by decreased rates of insulin-stimulated glucose uptake and utilization, reduced hexokinase II mRNA and enzyme production, and low basal levels of glucose 6-phosphate in insulin-sensitive skeletal muscle and adipose tissues. Hexokinase II is primarily expressed in muscle and adipose tissues where it catalyzes the phosphorylation of glucose to glucose 6-phosphate, a possible rate-limiting step for glucose disposal. To investigate the role of hexokinase II in insulin action and in glucose homeostasis as well as in mouse development, we generated a hexokinase II knock-out mouse. Mice homozygous for hexokinase II deficiency (HKII(-/-)) died at approximately 7.5 days post-fertilization, indicating that hexokinase II is vital for mouse embryogenesis after implantation and before organogenesis. HKII(+/-) mice were viable, fertile, and grew normally. Surprisingly, even though HKII(+/-) mice had significantly reduced (by 50%) hexokinase II mRNA and activity levels in skeletal muscle, heart, and adipose tissue, they did not exhibit impaired insulin action or glucose tolerance even when challenged with a high-fat diet.     

Recovery of plant communities after ecological restoration of forestry‐drained peatlands

Ecological restoration is expected to reverse the loss of biodiversity and ecosystem services. Due to the low number of well‐replicated field studies, the extent to which restoration recovers plant communities, and the factors underlying possible shortcomings, are not well understood even in medium term. We compared the plant community composition of 38 sites comprising pristine, forestry‐drained, and 5 or 10 years ago restored peatlands in southern Finland, with special interest in understanding spatial variation within studied sites, as well as the development of the numbers and the abundances of target species. Our results indicated a recovery of community composition 5–10 years after restoration, but there was significant heterogeneity in recovery. Plant communities farthest away from ditches were very similar to their pristine reference already 10 years after restoration. In contrast, communities in the ditches were as far from the target as the drained communities. The recovery appears to be characterized by a decline in the number and abundance of species typical to degraded conditions, and increase in the abundance of characteristic peatland species. However, we found no increase above the drained state in the number of characteristic peatland species. Our results suggest that there is a risk of drawing premature conclusions on the efficiency of ecological restoration with the current practice of short‐term monitoring. Our results also illustrate fine‐scale within‐site spatial variability in the degradation and recovery of the plant communities that should be considered when evaluating the success of restoration. Overall, we find the heterogeneous outcome of restoration observed here promising. However, low recovery in the number of characteristic species demonstrates the importance of prioritizing restoration sites, and addressing the uncertainty of recovery when setting restoration targets. It appears that it is easier to eradicate unwanted species than regain characteristic species by restoration.     

K121Q PC‐1 Gene Polymorphism Is Not Associated with Insulin Resistance in a Spanish Population

Objective : To investigate the effect of the K121Q plasma cell membrane glycoprotein (PC‐1) polymorphism on the components of the insulin resistance syndrome in a population‐based nationwide multicenter study in Spain. Research Methods and Procedures : The subjects of the study were 293 nonrelated adults (44.7% men and 55.3% women) ages 35 to 64 years randomly chosen from a nationwide population‐based survey on obesity and related conditions, including insulin resistance and cardiovascular risk factors. Obesity‐related anthropometric measurements included blood pressure, oral glucose tolerance test, lipid profile (total cholesterol, high‐density lipoprotein‐ and low‐density lipoprotein‐cholesterol, and triglycerides), plasma leptin, insulin levels by radioimmunoassay, and insulin resistance (homeostasis model assessment). K121Q PC‐1 genotypes were determined by restriction fragment‐length polymorphism‐polymerase chain reaction. Results : Overall Q allele frequency was 0.14, with no differences between obese and nonobese individuals (0.15 vs. 0.13). After adjustment for sex, age, BMI, and degree of glucose tolerance, the Q allele was associated with high plasma leptin and triglyceride levels, but not with insulin resistance. Discussion : The results showed that the K121Q PC‐1 polymorphism in the Spanish population has no significant impact on insulin sensitivity.     

A Deletion in the α2B‐Adrenergic Receptor Gene and Autonomic Nervous Function in Central Obesity

Objective: We investigated the impact of a three‐amino acid deletion (12Glu9) polymorphism in the α_2B‐adrenergic receptor gene on autonomic nervous function. The short form (Glu⁹/Glu⁹) of the polymorphism has previously been associated with a reduced basal metabolic rate in obese subjects. Because autonomic nervous function participates in the regulation of energy metabolism, there could be a link between this polymorphism and autonomic nervous function. Research Methods and Procedures: Data of a 10‐year follow‐up study with 126 nondiabetic control subjects and 84 type 2 diabetic patients were used to determine the effects of the 12Glu9 polymorphism on autonomic nervous function. A deep breathing test and an orthostatic test were used to investigate parasympathetic and sympathetic autonomic nervous function. In addition, cardiovascular autonomic function was studied using power spectral analysis of heart rate variability. Results: No significant differences were found in the frequency of the 12Glu9 deletion polymorphism between nondiabetic and diabetic subjects. The nondiabetic men with the Glu⁹/Glu⁹ genotype, especially those with abdominal obesity, had significantly lower total and low‐frequency power values in the power spectral analysis when compared with other men. Furthermore, in a longitudinal analysis of 10 years, the decrease in parasympathetic function was greater in nondiabetic men with the Glu⁹/Glu⁹ genotype than in the men with the Glu⁹/Glu¹² or Glu¹²/Glu¹² genotypes. Discussion: The results of the present study suggest that the 12Glu9 polymorphism of the α_2B‐adrenergic receptor gene modulates autonomic nervous function in Finnish nondiabetic men. In the nondiabetic men with the Glu⁹/Glu⁹ genotype, the general autonomic tone is depressed, and vagal activity especially becomes impaired with time. Furthermore, this association is accentuated by central obesity.     

The OSBP-related proteins: a novel protein family involved in vesicle transport,cellular lipid metabolism,and cell signalling

Proteins/genes showing high sequence homology to the mammalian oxysterol binding protein (OSBP) have been identified in a variety of eukaryotic organisms from yeast to man. The unifying feature of the gene products denoted as OSBP-related proteins (ORPs) is the presence of an OSBP-type ligand binding (LB) domain. The LB domains of OSBP and its closest homologue bind oxysterols, while data on certain other family members suggest interaction with phospholipids. Many ORPs also have a pleckstrin homology (PH) domain in the amino-terminal region. The PH domains of the family members studied in detail are known to interact with membrane phosphoinositides and play an important role in the intracellular targeting of the proteins. It is plausible that the ORPs constitute a regulatory apparatus that senses the status of specific lipid ligands in membranes, using the PH and/or LB domains, and mediates information to yet poorly known downstream machineries. Functional studies carried out on the ORP proteins in different organisms indicate roles of the gene family in diverse cellular processes including control of lipid metabolism, regulation of vesicle transport, and cell signalling events.