Matrix metalloproteinase-8 regulates transforming growth factor-β1 levels in mouse tongue wounds and fibroblasts in vitro

Matrix metalloproteinase-8 (MMP-8)-deficient mice (Mmp8-/-) exhibit delayed dermal wound healing, but also partly contradicting results have been reported. Using the Mmp8-/- mice we investigated the role of MMP-8 in acute wound healing of the mobile tongue, and analyzed the function of tongue fibroblasts in vitro. Interestingly, in the early phase the tongue wounds of Mmp8-/- mice healed faster than those of wild type (wt) mice resulting in significant difference in wound widths (P=0.001, 6–24 h). The Mmp8-/- wounds showed no change in myeloperoxidase positive myeloid cell count, but the level of transforming growth factor (TGF)-β1 was significantly increased (P=0.007) compared to the wt tongues. Fibroblasts cultured from wt tongues expressed MMP-8 and TGF-β1. However, higher TGF-β1 levels were detected in Mmp8-/- fibroblasts, and MMP-8 treatment decreased phosphorylated Smad-2 levels and α-smooth muscle actin expression in these fibroblasts suggesting reduced TGF-β1 signaling. Consistently, a degradation of recombinant TGF-β1 by MMP-8 decreased its ability to activate the signaling cascade in fibroblasts. Moreover, collagen gels with Mmp8-/- fibroblasts reduced more in size. We conclude that MMP-8 regulates tongue wound contraction rate and TGF-β1 levels. In vitro analyses suggest that MMP-8 may also play a role in regulating TGF-β1 signaling of stromal fibroblasts.     

Human primary motor cortex is both activated and stabilized during observation of other person's phasic motor actions

When your favourite athlete flops over the high-jump bar, you may twist your body in front of the TV screen. Such automatic motor facilitation, ‘mirroring’ or even overt imitation is not always appropriate. Here, we show, by monitoring motor-cortex brain rhythms with magnetoencephalography (MEG) in healthy adults, that viewing intermittent hand actions of another person, in addition to activation, phasically stabilizes the viewer''s primary motor cortex, with the maximum of half a second after the onset of the seen movement. Such a stabilization was evident as enhanced cortex–muscle coherence at 16–20 Hz, despite signs of almost simultaneous suppression of rolandic rhythms of approximately 7 and 15 Hz as a sign of activation of the sensorimotor cortex. These findings suggest that inhibition suppresses motor output during viewing another person''s actions, thereby withholding unintentional imitation.     

IL-17/Th17 Pathway Is Activated in Acne Lesions

The mechanisms of inflammation in acne are currently subject of intense investigation. This study focused on the activation of adaptive and innate immunity in clinically early visible inflamed acne lesions and was performed in two independent patient populations. Biopsies were collected from lesional and non-lesional skin of acne patients. Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed at the RNA and also protein level with real-time PCR (RT-PCR) and Luminex technology. Cytokines involved in Th17 lineage differentiation (IL-1β, IL-6, TGF-β, IL23p19) were remarkably induced at the RNA level. In addition, proinflammatory cytokines and chemokines (TNF-α, IL-8, CSF2 and CCL20), Th1 markers (IL12p40, CXCR3, T-bet, IFN-γ), T regulatory cell markers (Foxp3, IL-10, TGF-β) and IL-17 related antimicrobial peptides (S100A7, S100A9, lipocalin, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL-17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway is activated and may play a pivotal role in the disease process, possibly offering new targets of therapy.     

Risk-Taking Behavior in a Computerized Driving Task: Brain Activation Correlates of Decision-Making,Outcome, and Peer Influence in Male Adolescents

Increased propensity for risky behavior in adolescents, particularly in peer groups, is thought to reflect maturational imbalance between reward processing and cognitive control systems that affect decision-making. We used functional magnetic resonance imaging (fMRI) to investigate brain functional correlates of risk-taking behavior and effects of peer influence in 18–19-year-old male adolescents. The subjects were divided into low and high risk-taking groups using either personality tests or risk-taking rates in a simulated driving task. The fMRI data were analyzed for decision-making (whether to take a risk at intersections) and outcome (pass or crash) phases, and for the influence of peer competition. Personality test-based groups showed no difference in the amount of risk-taking (similarly increased during peer competition) and brain activation. When groups were defined by actual task performance, risk-taking activated two areas in the left medial prefrontal cortex (PFC) significantly more in low than in high risk-takers. In the entire sample, risky decision-specific activation was found in the anterior and dorsal cingulate, superior parietal cortex, basal ganglia (including the nucleus accumbens), midbrain, thalamus, and hypothalamus. Peer competition increased outcome-related activation in the right caudate head and cerebellar vermis in the entire sample. Our results suggest that the activation of the medial (rather than lateral) PFC and striatum is most specific to risk-taking behavior of male adolescents in a simulated driving situation, and reflect a stronger conflict and thus increased cognitive effort to take risks in low risk-takers, and reward anticipation for risky decisions, respectively. The activation of the caudate nucleus, particularly for the positive outcome (pass) during peer competition, further suggests enhanced reward processing of risk-taking under peer influence.     

DNA barcoding as a heuristic tool for classifying undescribed Nearctic Myrmica ants (Hymenoptera: Formicidae)

The Palearctic species of the ant genus Myrmica are well studied. In contrast, the taxonomy of the Nearctic species is outdated, making identification impossible. We collected Myrmica samples in the Holarctic and investigated their diversity using mtDNA data. We analysed a barcode sequence of the Cytochrome Oxidase I gene for 57 Palearctic and 293 Nearctic Myrmica samples. We used sequences of known Palearctic species to search for Myrmica barcode patterns. All but one Palearctic species groups were recovered. The Nearctic diversity was much higher than known. We retrieved the punctiventris, crassirugis and incompleta groups, and established nine additional tentative species groups. Genetic distance analysis revealed a large overlap of intra- and inter-specific distances in Palearctic species and species groups. We could not find a variation gap to separate Nearctic sequences into species with COI data only. Variation in scape morphology divided two genetic groups further. Scape morphology correlated with most molecular groups, except three specimens. Our results illustrate that barcoding, using only a limited amount of genetic information, cannot serve as a universal proxy for taxonomy and species demarcation. It should be considered a first step in understanding the taxonomic diversity of an unknown group of organisms.     

Investigating the effect of VEGF glycosylation on glycosaminoglycan binding and protein unfolding

VEGF165 binding to endothelial cells is potentiated by glycosaminoglycans (GAGs). Here, we have investigated the impact of VEGF165 N-glycosylation on GAG binding. Although glycosylated VEGF165 bound to heparin with only slightly higher affinity than non-glycosylated VEGF165, the natural ligand heparan sulfate induced a conformational change only in the glycosylated protein. Unfolding studies of the VEGF proteins indicated a stabilising effect of heparin on the growth factor structure.