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Despite their importance in carbon cycling and catchment runoff dynamics, the hydrology of temperate peat swamps in response to changing hydrometeorological conditions is largely understudied. We examined the importance of hydrogeomorphic settings in controlling hydrological connectivity and runoff in a temperate peat swamp in southern Ontario, Canada over two consecutive growing seasons with contrasting conditions (dry and wet years). We chose two different small‐scale hydrogeomorphic settings to investigate: (i) a site with strong wetland‐stream interactions (i.e., an unconfined stream channel; unconfined) and (ii) a site with limited wetland‐stream interactions (confined). During the wet year, the confined site exhibited a consistently gaining stream, maintaining lateral hydrological connectivity and yielding high runoff ratios, while during the dry year, the confined site lost water and experienced low runoff ratios during storm events. Overland flow at the unconfined site maintained a longitudinal hydrological connectivity delivering water to its sub‐catchment outflow, as reinforced by hydrochemical observations. This connectivity was maintained in the wet year but ceased in the dry year despite consistent upstream sub‐catchment water inflow due to high depression storage. Runoff ratios were reduced because of this hydrological disconnection. We highlight the importance of small‐scale hydrogeomorphic setting on peat swamp carbon storage as facilitated by the variation of within‐site hydrological connectivity and runoff, which also has important implications for downstream water quality. The unconfined site maintained a higher water table position in both years and has much greater peat carbon stocks. We suggest peat swamp channelization either naturally or through drainage decreases carbon stocks. [ABSTRACT FROM AUTHOR]

Ischemic damage is recognized to cause cardiomyocyte (CM) death and myocardial dysfunction, but the role of cell-matrix interactions and integrins in this process has not been extensively studied. Expression of α7β1D integrin, the dominant integrin in normal adult CMs, increases during ischemia/reperfusion (I/R), while deficiency of β1 integrins increases ischemic damage. We hypothesized that the forced overexpression of integrins on the CM would offer protection from I/R injury. Tg mice with CM-specific overexpression of integrin α7β1D exposed to I/R had a substantial reduction in infarct size compared with that of α5β1D-overexpressing mice and WT littermate controls. Using isolated CMs, we found that α7β1D preserved mitochondrial membrane potential during hypoxia/reoxygenation (H/R) injury via inhibition of mitochondrial Ca2+ overload but did not alter H/R effects on oxidative stress. Therefore, we assessed Ca2+ handling proteins in the CM and found that β1D integrin colocalized with ryanodine receptor 2 (RyR2) in CM T-tubules, complexed with RyR2 in human and rat heart, and specifically bound to RyR2 amino acids 165-175. Integrins stabilized the RyR2 interdomain interaction, and this stabilization required integrin receptor binding to its ECM ligand. These data suggest that α7β1D integrin modifies Ca2+ regulatory pathways and offers a means to protect the myocardium from ischemic injury.

The [alpha]7[beta]1 integrin is increased in skeletal muscle in response to injury-producing exercise, and transgenic overexpression of this integrin in mice protects against exercise-induced muscle damage. The present study investigates whether the increase in the [alpha]7[beta]1 integrin observed in wild-type mice in response to exercise is due to transcriptional regulation and examines whether mobilization of the integrin at the myotendinous junction (MTJ) is a key determinant in its protection against damage. A single bout of downhill running exercise selectively increased transcription of the [alpha]7 integrin gene in 5-wk-old wild-type mice 3 h postexercise, and an increased [alpha]7 chain was detected in muscle sarcolemma adjacent to tendinous tissue immediately following exercise. The [alpha]7B, but not [alpha]7A isoform, was found concentrated and colocalized with tenascin-C in muscle fibers lining the MTJ. To further validate the importance of the integrin in the protection against muscle damage following exercise, muscle injury was quantified in [alpha][7.sup.- /-] mice. Muscle damage was extensive in [alpha][7.sup.-/-] mice in response to both a single and repeated bouts of exercise and was largely restricted to areas of high MTJ concentration and high mechanical force near the Achilles tendon. These results suggest that exercise-induced muscle injury selectively increases transcription of the [alpha]7 integrin gene and promotes a rapid change in the [alpha]7[beta] integrin at the MTJ. These combined molecular and cellular alterations are likely responsible for integrin-mediated attenuation of exercise-induced muscle damage. exercise; injury; repeated bout effect; tenascin-C

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The metabolic syndrome is a group of disorders including obesity, insulin resistance, atherogenic dyslipidemia, hyperglycemia, and hypertension. To date, few animal models have been described to recapitulate the phenotypes of the syndrome. In this study, we generated and characterized two lines of triple-knockout mice that are deficient in either apolipoprotein E ([Apoe.sup.-/-]) or low-density lipoprotein receptor ([Ldlr.sup.-/-]) and express no leptin ([Lep.sup.ob/ob]) or apolipoprotein B-48 but exclusively apolipoprotein B-100 ([Apob.sup.100/100]). These two lines are referred to as Apoe triple-knockout-Apoe 3KO ([Apoe.sup.-/-][Apob.sup.100/100][Lep.sup.ob/ob]) and Ldlr triple-knockout-Ldlr 3KO ([Ldlr.sup.-/-][Apob.sup.100/100][Lep.sup.ob/ob]) mice. Both lines develop obesity, hyperinsulinemia, hyperlipidemia, hypertension, and atherosclerosis. However, only Apoe 3KO mice are hyperglycemic and glucose intolerant and are more obese than Ldlr 3KO mice. To evaluate the utility of these lines as pharmacological models, we treated both with leptin and found that leptin therapy ameliorated most metabolic derangements. Leptin was more effective in improving glucose tolerance in Ldlr 3KO than Apoe 3KO animals. The reduction of plasma cholesterol by leptin in Ldlr 3KO mice can be accounted for by its suppressive effect on food intake. However, in Apoe 3KO mice, leptin further reduced plasma cholesterol independently of its effect on food intake, and this improvement correlated with a smaller plaque lesion area. These effects suggest a direct role of leptin in modulating VLDL levels and, likewise, the lesion areas in VLDL-enriched animals. These two lines of mice represent new models with features of the metabolic syndrome and will be useful in testing therapies targeted for combating the human condition. atherosclerosis; leptin; hypercholesterolemia; diabetes: obesity

The dystrophin-glycoprotein complex maintains the integrity of skeletal muscle by associating laminin in the extracellular matrix with the actin cytoskeleton. Several human muscular dystrophies arise from defects in the components of this complex. The [[alpha].sub.7][[beta].sub.1]-integrin also binds laminin and links the extracellular matrix with the cytoskeleton. Enhancement of [[alpha].sub.7]-integrin levels alleviates pathology in [mdx/utrn.sup.-/-] mice, a model of Duchenne muscular dystrophy, and thus the integrin may functionally compensate for the absence of dystrophin. To test whether increasing [[alpha].sub.7]-integrin levels affects transcription and cellular functions, we generated [[alpha].sub.7]-integrin-inducible C2C12 cells and transgenic mice that overexpress the integrin in skeletal muscle. C2C12 myoblasts with elevated levels of integrin exhibited increased adhesion to laminin, faster proliferation when serum was limited, resistance to staurospofine-induced apoptosis, and normal differentiation. Transgenic expression of eightfold more integrin in skeletal muscle did not result in notable toxic effects in vivo. Moreover, high levels of [[alpha].sub.7]-integrin in both myoblasts and in skeletal muscle did not disrupt global gene expression profiles. Thus increasing integrin levels can compensate for defects in the extracellular matrix and cytoskeleton linkage caused by compromises in the dystrophin-glycoprotein complex without triggering apparent overt negative side effects. These results support the use of integrin enhancement as a therapy for muscular dystrophy. myoblast proliferation; integrin transgenic mice; microarray

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[[alpha].sub.7][[beta].sub.1]-Integrin links laminin in the extracellular matrix with the cell cytoskeleton and therein mediates transduction of mechanical forces into chemical signals. Muscle contraction and stretching ex vivo result in activation of intracellular signaling molecules that are integral to postexercise injury responses. Because [[alpha].sub.7][[beta].sub.1]-integrin stabilizes muscle and provides communication between the matrix and cytoskeleton, the role of this integrin in exercise-induced cell signaling and skeletal muscle damage was assessed in wild-type and transgenic mice over-expressing the [[alpha].sub.7]TBX2 chain. We report here that increasing [[alpha].sub.7][[beta].sub.1]integrin inhibits phosphorylation of molecules associated with muscle damage, including the mitogen-activated protein kinases (JNK, p38, and ERK), following downhill running. Likewise, activation of molecules associated with hypertrophy (AKT, mTOR, and [p70.sup.S6k]) was diminished in mice over-expressing integrin. While exercise resulted in Evans blue dye-positive fibers, an index of muscle damage, increased integrin protected mice from injury. Moreover, exercise leads to an increase in [[alpha].sub.7][[beta].sub.1] protein. These experiments provide the first evidence that [[alpha].sub.7] [[beta].sub.1]-integrin is a negative regulator of mechanotransduction in vivo and provides resistance to exercise-induced muscle damage. downhill running exercise; MAP kinase; AKT; mTOR; [p70.sup.S6k]

We showed previously that the expression of [[alpha].sub.7]-integrin in aortic vascular smooth muscle cells (VSMC) is enhanced in a rat model of atherosclerosis. In the present study, we investigated the effects of platelet-derived growth factor (PDGF) on [[alpha].sub.7]-integrin expression and VSMC adhesion and migration. Expression of the [[alpha].sub.7]-integrin gene was determined by real-time RT-PCR, whereas protein levels were determined by fluorescence-activated cell sorting analysis. PDGF increased [[alpha].sub.7] cell surface protein expression (12 and 24 h: 3.3 [+ or -] 0.8- and 3.6 [+ or -] 0.4-fold, P < 0.05 vs. control) and mRNA levels (24 h: 3.1-fold, P < 0.05 vs. control) in a time-dependent manner. Actinomycin D and cycloheximide attenuated PDGF-induced increases in [[alpha].sub.7]-integrin, indicating the involvement of de novo mRNA and protein synthesis. Treatment with the MAPK inhibitors PD-98059, SP-600125, and SB-203580 attenuated PDGF-induced increases in mRNA. In contrast, PD-98059 and SP-600125, but not SB-203580, attenuated PDGF-induced increases in cell surface protein levels. PDGF-treated VSMC adhered to laminin more efficiently (42 [+ or -] 6% increase, P < 0.01), and this increase was partially inhibited by anti-[[alpha].sub.7]-integrin function-blocking antibody. However, PDGF did not alter migration on laminin, and there was no effect of the anti-[[alpha].sub.7]-integrin function-blocking antibody on basal or PDGF-stimulated migration, lmmunofluorescence imaging revealed an increase in [[alpha].sub.7]-integrin distribution along the stress fibers. Together, these observations indicate that PDGF enhances [[alpha].sub.7]-integrin expression in VSMC and promotes [[alpha].sub.7]-vintegrin-mediated adhesion to laminin. vascular injury; laminin; mitogen-activated protein kinase

Injury of vascular smooth muscle cells (VSMCs) by allylamine (AAM) leads to phenotypic changes associated with atherogenic progression including increased proliferation, migration, and alterations in cell adhesion. In the present study, the relationship between AAM-induced vascular injury and expression of the [[alpha].sub.7]-integrin subunit was investigated. The [[alpha].sub.7]-mRNA and protein expression were examined using real-time RT-PCR, fluorescence-activated cell sorting analysis (FACS), immunohistochemistry, and immunoblotting. In cultured VSMCs from aortas of AAM-treated rats (70 mg/kg for 20 days), [[alpha].sub.7]-mRNA levels were increased more than twofold compared with control cells. No change was seen in [[beta].sub.1]-integrin expression. FACS analysis revealed increased cell surface expression of [[alpha].sub.7]-protein (25 [+ or -] 9%; [sup.*]P < 0.05). AAM treatment of naive VSMCs enhanced [[alpha].sub.7]-mRNA expression (2.4 [+ or -] 0.7-fold, mean [+ or -] SE; ][sup.*]P < 0.05). The increased [[alpha].sub.7]-mRNA expression was attenuated by the amine oxidase inhibitor semicarbazide and the antioxidant pyrrolidine dithiocarbamate, which confirms a role for oxidative stress in modulating [[alpha].sub.7]-expression. In vivo [[alpha].sub.7]-mRNA and protein expression were enhanced in the aortas of AAM-treated rats. In addition, increased [[alpha].sub.7]-integrin expression facilitated AAM VSMC adhesion to laminin more efficiently compared with control (51 [+ or -] 2%; [sup.*]P < 0.05). Chemical injury induced by AAM significantly enhances [[alpha].sub.7]-integrin expression in VSMCs. These findings implicate for the first time the expression of [[alpha].sub.7]-integrin during the response of VSMCs to vascular injury. aorta; cell adhesion; laminin; vascular injury

Integrins are [alpha][beta] transmembrane receptors that function in key cellular processes, including cell adhesion, differentiation, and extracellular matrix deposition through interactions with extracellular, membrane, and cytoplasmic proteins. We previously identified and cloned a muscle [beta]1 integrin cytoplasmic binding protein termed MIBP and found that the expression level of MIBP is critical in the decision-making process of terminal myogenic differentiation. We report here that MIBP interacts with the [alpha]7[beta]1 integrin but not the [alpha]5[beta]1 integrin in C2C12 myoblasts, suggesting an important role of integrin [alpha] chains in the regulation of the [beta]1-MIBP interaction. Furthermore, consistent with its selective binding activity toward the [alpha]7[beta]1 laminin receptor, we have found that overexpression of MIBP in C2C12 myoblasts resulted in a significant reduction of cell adhesion to laminin and inhibition of laminin matrix deposition. By contrast, neither cell adhesion to fibronectin nor fibronectin matrix deposition was significantly altered in cells overexpressing MIBP. Finally, we show that both the protein level and tyrosine phosphorylation of paxillin, a key signaling molecule involved in the cellular control of myogenic differentiation, are increased by MIBP. These results suggest that MIBP functions in the control of myogenic differentiation by regulating [alpha]7[beta]1 integrin-mediated cell interactions with laminin matrix and intracellular signaling through paxillin. Keywords: MIBP; Integrin; Laminin; Cell adhesion; Signaling

Bone resorption and remodeling is a very precisely controlled body process that requires osteoclasts to function as a part of the process. Mice that lack the TNF receptor-associated factor 6 (TRAF6) are osteopetrotic with defects in tooth eruption and bone remodeling, the result of impaired osteoclast activity. TRAF6 has been shown to be crucial in IL-1 and CD40 signaling and also in lipopolysaccharide (LPS) signaling, which would not be expected. It is essential for survival perinatally and postnatally, also unexpected.

Research was conducted to demonstrate the role of a laminin receptor protein in the formation of neuromuscular junctions. The data indicate that laminin, agrin, and integrin all participate co-operatively in the process.