Living in the branches: population dynamics and ecological processes in dendritic networks.

Spatial structure regulates and modifies processes at several levels of ecological organization (e.g. individual/genetic, population and community) and is thus a key component of complex systems, where knowledge at a small scale can be insufficient for understanding system behaviour at a larger scale.

Role of the mitogen-activated protein kinases in cytokine-mediated inhibition of insulin gene expression.

Background: Following islet transplant, inflammatory cells in the vicinity of the transplant graft elaborate cytokines that contribute to islet graft dysfunction. To better understand the mechanism for this effect of cytokines on graft function, we examined the impact of cytokines on intracellular signaling and insulin promoter activity in pancreatic beta cells.

Methods: Two pancreatic beta cell lines, RINm5F and MIN6 cells, were transfected with a rat insulin promoter (RIP) luciferase fusion gene and treated with a combination of cytokines, including 5 ng/mL interleukin-1beta + 10 ng/mL tumor necrosis factor alpha + 25 ng/mL interferon-gamma.

Polymer scaffolds as synthetic microenvironments for extrahepatic islet transplantation.

Background: Problems associated with the hepatic transplantation of islets may preclude the broad application of islet transplantation. Thus, we sought to develop an approach to the extrahepatic transplantation of islets using a synthetic biodegradable polymer scaffold.

Methods: Microporous polymer scaffolds that allow vascular ingrowth and nutrient diffusion from host tissues were fabricated from copolymers of lactide and glycolide.

Linking direct and indirect data on dispersal: isolation by slope in a headwater stream salamander.

There is growing recognition of the need to incorporate information on movement behavior in landscape-scale studies of dispersal. One way to do this is by using indirect indices of dispersal (e.g.

The ether lipid inositol-C2-PAF is a potent inhibitor of cell proliferation in HaCaT cells.

The search for specific anticancer drugs that do not interfere with DNA synthesis or influence the cytoskeleton has led to the development of modified phospholipids with antiproliferative properties. These compounds cause remodeling of the structure and function of plasma membranes. Recently, we described novel compounds, the glycosidated phospholipids, that surprisingly inhibit cell proliferation.

4-Anilinoquinazolines with Lavendustin A subunit as inhibitors of epidermal growth factor receptor tyrosine kinase: syntheses, chemical and pharmacological properties.

4-Anilinoquinazoline derivatives are widely investigated due to their potent epidermal growth factor receptor (EGFR) tyrosine kinase inhibitory activity. Two 4-anilinoquinazolines with Lavendustin A subunit (10a,b) were synthesized and examined for their EGFR tyrosine kinase inhibitory activity as well as their antiproliferative properties on variant human cancer cell lines. Both compounds maintained their EGFR tyrosine kinase inhibitory activity at the 10-7 M level and led to significant growth inhibition in certain leukemia, non-small cell lung cancer (NSCLC), ovarian cancer, renal cancer and breast cancer cell lines with GI50 values at the 10-6 M level.

A biomechanical comparison of repair techniques for type II SLAP lesions.

Background: Multiple options exist for repair of superior labral tears.

Purpose: To compare commonly used fixation techniques for superior labral tears.

Study Design: Biomechanical cadaveric study.

Clinical islet transplantation.

Type 1 diabetes affects over 1 million persons in the United States, with over 30,000 new cases diagnosed annually. Transplantation of new insulin-producing b cells, in the form of the whole pancreas or isolated islets, has been shown to ameliorate the disease by eliminating the need for exogenous insulin and normalizing glycosylated hemoglobin levels. Islet transplants are a particularly attractive form of therapy because they are a minimally invasive procedure and are more likely to be scaled-up to treat the large numbers of people affected by diabetes.

Activation of phosphatidylinositol 3-kinase contributes to insulin-like growth factor I-mediated inhibition of pancreatic beta-cell death.

To begin to determine whether IGF-I treatment represents a potential means of enhancing the survival of islet cell grafts after transplantation, the present studies established a model of beta-cell death secondary to loss of trophic support and examined the ability of IGF-I to prevent cell death. The studies were performed using the rat pancreatic beta-cell line, INS-1. Incubating INS-1 cells in RPMI 1640 and 0.

Landscape-scale spatial population dynamics in human-impacted stream systems.

The movement of individuals among populations can be critical in preventing local and landscape-scale species extinctions in systems exposed to human perturbation. Current understanding of spatial population dynamics in streams is largely limited to the reach scale and is therefore inadequate to address species response to spatially extensive perturbation. Using model simulations, I examined species response to perturbation in a drainage composed of multiple, hierarchically arranged stream-patches connected by in-stream and overland pathways of dispersal.

Local and Landscape-Scale Predictors of Salamander Abundance in New Hampshire Headwater Streams.

We investigated the response of Gyrinophilus porphyriticus ( Plethodontidae), the spring salamander, to timber harvest in headwater streams in New Hampshire ( U.S.A.

LY 294002, an inhibitor of phosphatidylinositol 3-kinase, inhibits GH-mediated expression of the IGF-I gene in rat hepatocytes.

The signal transduction pathways that mediate GH-dependent regulation of IGF-I gene expression remain poorly defined. To establish a GH-responsive in vitro model system to study the effect of GH on the expression of the endogenous IGF-I gene, primary hepatocytes from adult male rats were prepared. These cells expressed both the GH receptor and the IGF-I gene, as demonstrated using a ribonuclease protection assay.

Heritability of obesity-related traits among Nigerians, Jamaicans and US black people.

Objective: The mean values for anthropometric traits vary across population groups and this variation is clearly determined for the most part by the environment. The familiarity of anthropometric traits also varies in reports from different populations, although this variation has not been shown to follow a consistent pattern. To examine whether heritability is influenced by socio-cultural factors, we conducted a cross-cultural study of populations of the African diaspora.

The role of phosphatidylinositol 3-kinase and the mitogen-activated protein kinases in insulin-like growth factor-I-mediated effects in vascular endothelial cells.

Despite an improved understanding of the molecular mechanisms of insulin-like growth factor-I (IGF-I) signaling and the recognition that IGF-I mediates many effects in endothelial cells, some of which may be important for atherosclerosis, little is known about the signal transduction pathways that mediate the effects of IGF-I in endothelial cells. To that end, we examined the signaling pathways activated by IGF-I in endothelial cells and their contribution to IGF-I-stimulated endothelial cell migration and nuclear factor (NF)-kappaB-dependent transcription. Treatment of bovine pulmonary artery endothelial cells (PAEC) with IGF-I activated the mitogen-activated protein kinases extracellular signal-regulated kinase (ERK)1/2 and ERK5.

The beta 3-adrenergic receptor gene and obesity in a population sample of African Americans.

Objective: To examine the role of the Trp64Arg polymorphism in the beta 3-adrenergic receptor gene and the beta 3-adrenergic receptor gene locus in obesity-related traits in African Americans.

Subjects: A total of 687 individuals representing 193 African American families who were residents of metropolitan Chicago.

Measurements: Genotyping of the Trp64Arg polymorphism in the beta 3-adrenergic receptor gene and three microsatellite markers flanking the beta 3-adrenergic receptor gene (ADRB3) locus and measuring various obesity-related traits, including body mass index (BMI), fat-free mass, fat mass, percentage fat mass, waist circumference and serum lipid levels.

Activation of members of the mitogen-activated protein kinase family by glucose in endothelial cells.

To better understand the molecular mechanisms for hyperglycemia-induced proatherogenic changes in endothelial cells, the effect of high glucose on activation of members of the mitogen-activated protein kinase (MAPK) family, including c-Jun NH(2)-terminal kinase (JNK), extracellular signal-regulated kinase (ERK)-1, -2, and -5, and p38 kinase, was examined in bovine pulmonary artery endothelial cells (PAEC). Glucose, fructose, and raffinose induced a concentration-dependent decrease in PAEC growth. Addition of 25 mM glucose, fructose, or raffinose to normal growth medium stimulated an approximately twofold increase in JNK1 activity that was maximal after 24 h, whereas only glucose markedly increased ERK5 activity.

Wortmannin and LY294002 inhibit myo-inositol accumulation by cultured bovine aorta endothelial cells and murine 3T3-L1 adipocytes.

We have previously reported that myo-inositol uptake and metabolism is reduced in human fibroblasts derived from patients with ataxia telangiectasia (AT). Treating normal fibroblasts with 10-100 microM wortmannin duplicates some of the phenotypic properties of AT fibroblasts including the decrease in myo-inositol accumulation. In the present study we examined whether treatment of other types of mammalian cells with wortmannin or LY294002 altered myo-inositol uptake.

Lack of association between the -308 polymorphism of the tumor necrosis factor-alpha gene and the insulin resistance syndrome.

Background: Previous studies have demonstrated a role for tumor necrosis factor-alpha (TNF-alpha) in insulin resistance. A polymorphic variant of the TNF-alpha gene, the TNF2 allele, which is a guanine to adenine polymorphism at position -308 in the TNF-alpha promoter, is associated with higher basal and inducible promoter activity. The present study examined whether the TNF2 allele was associated with altered levels of different components of the insulin resistance syndrome, clustering of these components, or the 10-year change in the level of these components.

Abnormal glucose metabolism and pancreatic cancer mortality.

Context: Previous studies reported an increased risk of pancreatic cancer among persons with diabetes. Few data exist, however, on the association of postload plasma glucose concentration with pancreatic cancer, which could provide insight into the role of abnormal glucose metabolism in the etiology of pancreatic cancer.

Objective: To determine the independent association between postload plasma glucose concentration and risk of pancreatic cancer mortality among persons without self-reported diabetes.

Normalization of hyperosmotic-induced inositol uptake by renal and endothelial cells is regulated by NF-kappaB.

Hyperosmolarity is a stress factor that has been shown to cause an increase in the transcription of the Na(+)-dependent myo-inositol cotransporter (SMIT). However, regulation of the reversion of SMIT mRNA levels and transporter activity following removal of hyperosmotic stress is less understood. Previously we have shown that postinduction normalization of SMIT mRNA levels and myo-inositol accumulation following removal of hyperosmotic stress is inhibited by actinomycin D and cycloheximide, suggesting that normalization requires RNA transcription and protein synthesis.

Insulin-like growth factor I activates c-Jun N-terminal kinase in MCF-7 breast cancer cells.

Insulin-like growth factor I (IGF-I) is an important mediator of breast cancer cell growth, although the signaling pathways important for IGF-I-mediated effects in breast cancer cells are still being elucidated. We had demonstrated previously that increased intracellular cAMP in MCF-7 breast cancer cells inhibited cell growth and IGF-I-induced gene expression, as determined using a reporter gene assay. This effect of cAMP on IGF-I signaling was independent of IGF-I-induced activation of the mitogen-activated protein kinases extracellular signal-regulated kinases 1 and 2 (ERK1 and -2).

Cyclic pull-out strength of hamstring tendon graft fixation with soft tissue interference screws. Influence of screw length.

Blunt-threaded interference screws used for fixation of hamstring tendons in anterior cruciate ligament reconstructions provide aperture fixation and may provide a biomechanically more stable graft than a graft fixed further from the articular surface. It is unknown if soft tissue fixation strength using interference screws is affected by screw length. We compared the cyclic and time-zero pull-out forces of 7 x 25 mm and 7 x 40 mm blunt-threaded metal interference screws for hamstring graft tibial fixation in eight paired human cadaveric specimens.

Surgical anatomy of the posterior shoulder: effects of arm position and anterior-inferior capsular shift.

The purposes of this study were to evaluate anatomically various surgical intervals to the posterior shoulder and to determine the effects of varying arm positions and anterior-inferior capsular shift (AICS) on the relation of the posterior neurovascular structures to fixed bony landmarks. Fourteen cadaveric shoulders were dissected. The posterior surgical anatomy was defined, and the distances from fixed bony landmarks to neurovascular and musculotendinous structures were determined with digital calipers.