Integrin alpha2beta1 is the required receptor for endorepellin angiostatic activity

Endorepellin, the C-terminal module of perlecan, has angiostatic activity. Here we provide definitive genetic and biochemical evidence that the functional endorepellin receptor is the alpha2beta1 integrin. Notably, the specific endorepellin binding to the receptor was cation-independent and was mediated by the alpha2 I domain. We show that the anti-angiogenic effects of endorepellin cannot occur in the absence of alpha2beta1. Microvascular endothelial cells from alpha2beta1(-/-) mice, but not those isolated from either wild-type or alpha1beta1(-/-) mice, did not respond to endorepellin. Moreover, syngeneic Lewis lung carcinoma xenografts in alpha2beta1(-/-) mice failed to respond to systemic delivery of endorepellin. In contrast, endorepellin inhibited tumor growth and angiogenesis in the wild-type mice expressing integrin alpha2beta1. We conclude that the angiostatic effects of endorepellin in vivo are mediated by a specific interaction of endorepellin with the alpha2beta1 integrin receptor.     

Above- and belowground fluxes of methane from boreal dwarf shrubs and Pinus sylvestris seedlings

Plant and Soil - Legume break crops provide a series of agronomic benefits to the following wheat crop in a rotation. Phosphorus-efficient break-crop plants can mobilise P from non-labile pools in...     

Social implications of fission in wild Formosan macaques at Mount Longevity,Taiwan

Group fission in non-human primates has long been proposed to result from interactions between ecological and social factors. Several studies have documented possible causes for group fission, but its proximate causes and ultimate adaptive values are not yet fully understood. We have examined the existing hypotheses on fission from long-term demographic data of Formosan macaques inhabiting the lowland rainforest at Mt Longevity, Taiwan. Five cases of fission occurred in four social groups. We have recorded two types of fission: one involving the separation of a high-ranking adult male and multiple adult females, the other initiated by adult females from main groups. Five adult females immigrated and emigrated a few times between the main and branch groups (oscillation) in three fission events. Data presented in this study are consistent with the prediction that low-ranking females split from main groups when their fitness costs increase due to ecological pressure or population growth. However, their reproductive success may decrease after fission due to a high rate of intra-group competition. Nevertheless, it is beneficial for males to be involved in fission since this increases reproductive benefits by decreasing the sex ratio in small newly formed groups.     

The effects of habitat edges and trampling on understorey vegetation in urban forests in Helsinki,Finland

Question: How do habitat edges and trampling affect mesic (Myrtillus type) understorey vegetation in fragmented urban forests, and what are the relative strengths and spatial extent of these effects? Location: The city of Helsinki, southern Finland. Methods: Vegetation sample plots were placed at different distances from the forest edge. At each distance we selected plots on, next to and away from paths of different levels of wear, and the covers and frequencies of plant species were sampled. We used generalized linear mixed models and ordination techniques to test our hypotheses. Results: The effect of the edge penetrated up to 50 m into the forest interior. Only light effects of trampling were found in seemingly untrampled areas, in addition to the direct effects of trampling on the paths. Both trampling and edge effects changed the forest understorey species composition. Trampling changed plant species composition locally on paths, and provided opportunities for new species to establish in previously unbroken forest vegetation. Urban forest edges were characterised by species better adapted to sunny, warm and dry conditions. These species, such as grasses, replaced more sensitive forest species, such as dwarf shrubs and mosses. We observed a large number of light demanding deciduous trees at the edges, which may be one of the factors increasing soil fertility and consequently promoting the high abundance of fast growing species, such as grasses and herbs related to more fertile site types. Conclusions: We recommend that urban forest fragments left within urban development should be at least 2–3 ha in size and that the shape of the patch and the number of potential recreational users should be taken into account when preserving true forest understorey vegetation from the effects of edges and trampling.     

Early life environment and snoring in adulthood

Background

To our knowledge, no studies of the possible association of early life environment with snoring in adulthood have been published. We aimed to investigate whether early life environment is associated with snoring later in life.

Methods

A questionnaire including snoring frequency in adulthood and environmental factors in early life was obtained from 16,190 randomly selected men and women, aged 25–54 years, in Sweden, Norway, Iceland, Denmark and Estonia (response rate 74%).

Results

A total of 15,556 subjects answered the questions on snoring. Habitual snoring, defined as loud and disturbing snoring at least 3 nights a week, was reported by 18%. Being hospitalized for a respiratory infection before the age of two years (adjusted odds ratio (OR) = 1.27; 95% confidence interval (CI) 1.01–1.59), suffering from recurrent otitis as a child (OR = 1.18; 95%CI 1.05–1.33), growing up in a large family (OR = 1.04; 95%CI 1.002–1.07) and being exposed to a dog at home as a newborn (OR = 1.26; 95%CI 1.12–1.42) were independently related to snoring later in life and independent of a number of possible confounders in adulthood. The same childhood environmental factors except household size were also related with snoring and daytime sleepiness combined.

Conclusion

The predisposition for adult snoring may be partly established early in life. Having had severe airway infections or recurrent otitis in childhood, being exposed to a dog as a newborn and growing up in a large family are environmental factors associated with snoring in adulthood.     

Do male golden egg bugs carry eggs they have fertilized? A microsatellite analysis

In the golden egg bug, Phyllomorpha laciniata (Heteroptera,Coreidae), both males and females carry eggs on their back.Although females cannot carry their own eggs, males may carryeggs that they have fertilized. If males carry eggs they havefertilized, their behavior may be interpreted as paternal care.In this article, we provide genetic data for paternity assignmentof eggs carried by 40 males collected from the field. The malesand the eggs were typed by using four highly polymorphic microsatelliteDNA markers. Out of the 247 eggs typed, 87% were excluded fromthe father-offspring relationship based on single-locus (leastconservative exclusion) mismatches. Under the more conservative(exclusion by at least two single locus mismatches) method,78% of the eggs were nonpaternal. Relatedness estimates furthersupported our paternity analyses. The average relatedness ofthe eggs to the carrying males was low (b_em = -0.052 ±0.024 SE). Within the population, males were unrelated to eachother (b_mm = -0.004 ± 0.0002 SE), as were the eggs carriedby individual males (b_eggs = -0.004 ± 0.0001 SE). Thisfirst genetic study on the breeding system of the golden eggbugs did not find any support for the claim that egg carryingfunctioned as paternal care, nor did it support kin selectionas explanation for conspecific egg carrying.     

Preattentive auditory information processing under exposure to the 902 MHz GSM mobile phone electromagnetic field: A mismatch negativity (MMN) study

Previous studies on the effects of the mobile phone electromagnetic field (EMF) on various event‐related potential (ERP) components have yielded inconsistent and even contradictory results, and often failed in replication. The mismatch negativity (MMN) is an auditory ERP component elicited by infrequent (deviant) stimuli differing in some physical features from the repetitive frequent (standard) stimuli in a sound sequence. The MMN provides a sensitive measure for cortical auditory stimulus feature discrimination, regardless of attention and other contaminating factors. In this study, MMN responses to duration, intensity, frequency, and gap changes were recorded in healthy young adults (n = 17), using a multifeature paradigm including several types of auditory change in the same stimulus sequence, while a GSM mobile phone was placed on either ear with the EMF (902 MHz pulsed at 217 Hz; SAR_1g = 1.14 W/kg, SAR_10g = 0.82 W/kg, peak value = 1.21 W/kg, measured with an SAM phantom) on or off. An MMN was elicited by all deviant types, while its amplitude and latency showed no significant differences due to EMF exposure for any deviant types. In the present study, we found no conclusive evidence that acute exposure to GSM mobile phone EMF affects cortical auditory change detection processing reflected by the MMN. Bioelectromagnetics 30:241–248, 2009. © 2009 Wiley‐Liss, Inc.     

Dexamethasone downregulates the expression of parathyroid hormone-related protein (PTHrP) in mesenchymal stem cells

Parathyroid hormone-related protein (PTHrP) has been shown to have anabolic effects in women with postmenopausal osteoporosis. PTHrP promotes the recruitment of osteogenic cells and prevents apoptotic death of osteoblasts and osteocytes. The receptor responsible for the effects of PTHrP is the common PTH/PTHrP receptor (PTH1R). Glucocorticoids (GC) are commonly used as drugs to treat inflammatory diseases. Long-term GC treatments are often associated with bone loss which can lead to GC-induced osteoporosis. The aim of this work was to study the effects of the glucocorticoid dexamethasone (Dex) on the expression of PTHrP and PTH1R in adult human mesenchymal stem cells, the progenitor cells of osteoblasts.Adult human mesenchymal stem cells (hMSC) were cultured and differentiated by standard methods. The expression of PTHrP and PTH1R mRNA was assayed by real-time qPCR. The PTHrP release into the culture media was measured by an immunoradiometric assay.Treatment with Dex (10 nM) resulted in an 80% drop in the PTHrP release within 6 h. A 24 h Dex treatment also reduced the expression of PTHrP mRNA by up to 90%. The expression of PTH1R receptor mRNA was simultaneously increased up to 20-fold by 10 nM Dex. The effects of Dex on PTHrP and PTH1R were dose-dependent and experiments with the GC-receptor antagonist mifepristone showed an involvement of GC-receptors in these effects. In addition to the Dex-induced effects on PTHrP and PTH1R, Dex also increased mineralization and the expression of the osteoblast markers Runx2 and alkaline phosphatase. In our studies, we show that dexamethasone decreases the expression of PTHrP and increases the expression of the PTH1R receptor. This could have an impact on PTHrP-mediated anabolic actions on bone and could also affect the responsiveness of circulating PTH. The results indicate that glucocorticoids affect the signalling pathway of PTHrP by regulating both PTHrP and PTH1R expression and these mechanisms could be involved in glucocorticoid-induced osteoporosis.     

Removal of cell surface heparan sulfate increases TACE activity and cleavage of ErbB4 receptor

Background  

Nuclear localization of proteolytically formed intracellular fragment of ErbB4 receptor tyrosine kinase has been shown to promote cell survival, and nuclear localization of ErbB4 receptor has been described in human breast cancer. Tumor necrosis factor alpha converting enzyme (TACE) initiates the proteolytic cascade leading to ErbB4 intracellular domain formation. Interactions between matrix metalloproteases and heparan sulfate have been described, but the effect of cell surface heparan sulfate on TACE activity has not been previously described.