Keep Your Opponents Close: Social Context Affects EEG and fEMG Linkage in a Turn-Based Computer Game

In daily life, we often copy the gestures and expressions of those we communicate with, but recent evidence shows that such mimicry has a physiological counterpart: interaction elicits linkage, which is a concordance between the biological signals of those involved. To find out how the type of social interaction affects linkage, pairs of participants played a turn-based computer game in which the level of competition was systematically varied between cooperation and competition. Linkage in the beta and gamma frequency bands was observed in the EEG, especially when the participants played directly against each other. Emotional expression, measured using facial EMG, reflected this pattern, with the most competitive condition showing enhanced linkage over the facial muscle-regions involved in smiling. These effects were found to be related to self-reported social presence: linkage in positive emotional expression was associated with self-reported shared negative feelings. The observed effects confirmed the hypothesis that the social context affected the degree to which participants had similar reactions to their environment and consequently showed similar patterns of brain activity. We discuss the functional resemblance between linkage, as an indicator of a shared physiology and affect, and the well-known mirror neuron system, and how they relate to social functions like empathy.     

Juvenile parkinsonism,hypogonadism and Leigh-like MRI changes in a patient with m.4296G>A mutation in mitochondrial DNA

Leigh syndrome is a mitochondrial disease with considerable clinical and genetic variation. We present a 16-year-old boy with Leigh-like syndrome and broad developmental retardation, parkinsonism and hypogonadism. Sequencing of the entire mitochondrial DNA from blood revealed the m.4296G>A mutation in the MT-TI gene. The mutation was heteroplasmic with a 95% proportion of the mutant genome, while the proportion was 58% in the blood of the patient's clinically healthy mother. Our results suggest that m.4296G>A is pathogenic in humans, and that the phenotype related to this change includes Leigh-like syndrome in adolescence with parkinsonism and hypogonadism, in addition to the previously reported early infantile Leigh syndrome.     

Activation of Hypoxia Response in Endothelial Cells Contributes to Ischemic Cardioprotection

Small-molecule inhibition of hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs) is being explored for the treatment of anemia. Previous studies have suggested that HIF-P4H-2 inhibition may also protect the heart from an ischemic insult. Hif-p4h-2^gt/gt mice, which have 76 to 93% knockdown of Hif-p4h-2 mRNA in endothelial cells, fibroblasts, and cardiomyocytes and normoxic stabilization of Hif-α, were subjected to ligation of the left anterior descending coronary artery (LAD). Hif-p4h-2 deficiency resulted in increased survival, better-preserved left ventricle (LV) systolic function, and a smaller infarct size. Surprisingly, a significantly larger area of the LV remained perfused during LAD ligation in Hif-p4h-2^gt/gt hearts than in wild-type hearts. However, no difference was observed in collateral vessels, while the size of capillaries, but not their number, was significantly greater in Hif-p4h-2^gt/gt hearts than in wild-type hearts. Hif-p4h-2^gt/gt mice showed increased cardiac expression of endothelial Hif target genes for Tie-2, apelin, APJ, and endothelial nitric oxide (NO) synthase (eNOS) and increased serum NO concentrations. Remarkably, blockage of Tie-2 signaling was sufficient to normalize cardiac apelin and APJ expression and resulted in reversal of the enlarged-capillary phenotype and ischemic cardioprotection in Hif-p4h-2^gt/gt hearts. Activation of the hypoxia response by HIF-P4H-2 inhibition in endothelial cells appears to be a major determinant of ischemic cardioprotection and justifies the exploration of systemic small-molecule HIF-P4H-2 inhibitors for ischemic heart disease.     

Life history of the Glanville fritillary butterfly in fragmented versus continuous landscapes

Habitat loss and fragmentation threaten the long‐term viability of innumerable species of plants and animals. At the same time, habitat fragmentation may impose strong natural selection and lead to evolution of life histories with possible consequences for demographic dynamics. The Baltic populations of the Glanville fritillary butterfly (Melitaea cinxia) inhabit regions with highly fragmented habitat (networks of small dry meadows) as well as regions with extensive continuous habitat (calcareous alvar grasslands). Here, we report the results of common garden studies on butterflies originating from two highly fragmented landscapes (FL) in Finland and Sweden and from two continuous landscapes (CL) in Sweden and Estonia, conducted in a large outdoor cage (32 by 26 m) and in the laboratory. We investigated a comprehensive set of 51 life‐history traits, including measures of larval growth and development, flight performance, and adult reproductive behavior. Seventeen of the 51 traits showed a significant difference between fragmented versus CL. Most notably, the growth rate of postdiapause larvae and several measures of flight capacity, including flight metabolic rate, were higher in butterflies from fragmented than CL. Females from CL had shorter intervals between consecutive egg clutches and somewhat higher life‐time egg production, but shorter longevity, than females from FL. These results are likely to reflect the constant opportunities for oviposition in females living in continuous habitats, while the more dispersive females from FL allocate more resources to dispersal capacity at the cost of egg maturation rate. This study supports theoretical predictions about small population sizes and high rate of population turnover in fragmented habitats selecting for increased rate of dispersal, but the results also indicate that many other life‐history traits apart from dispersal are affected by the degree of habitat fragmentation.     

The dibenzodioxocin lignin substructure is abundant in the inner part of the secondary wall in Norway spruce and silver birch xylem

A specific condensed lignin substructure, dibenzodioxocin, was immunolocalized in differentiating cell walls of Norway spruce (Picea abies (L.) H. Karsten) and silver birch (Betula pendula Roth) xylem. A fluorescent probe, Alexa 488 was used as a marker on the dibenzodioxocin-specific secondary antibody. For the detection of this lignin substructure, 25-m cross-sections of xylem were viewed with a confocal laser-scanning microscope with fluorescein isothiocyanate fluorescence filters. In mature cells, fluorescence was detected in the S3 layer of the secondary wall in both tree species, but it was more intense in Norway spruce than in silver birch. In silver birch most of the signal was detected in vessel walls and less in fiber cell walls. In very young tracheids of Norway spruce and vessels and fibers of silver birch, where secondary cell wall layers were not yet formed, the presence of the dibenzodioxocin structure could not be shown.Abbreviation CLSM confocal laser-scanning fluorescence microscopy     

Mucopolysaccharidosis IVA: characterization of a common mutation found in Finnish patients with attenuated phenotype

Mucopolysaccharidosis IVA (MPS IVA) is caused by the deficiency of the lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase encoded by the GALNS gene on chromosome 16. We describe, in detail, the clinical phenotype of five patients from three unrelated Finnish families and have characterized the disease-causing mutations in GALNS. Genotypes of the patients are D60N/A291T, D60N/W230X, and D60N/1374delT. Mutation 1374delT introduces premature termination of GALNS. Cells over-expressing the novel mutation W230X and A291T had no residual GALNS activity, whereas D60N gave 12.2% residual activity compared with the wild type. Co-transfection of D60N/A291T and D60N/W230X showed 5.5% and 6.7% of wild type activity, respectively. The precursor proteins of D60N and A291T were observed at 55 kDa and 57 kDa, respectively, whereas there was no detectable band in cells over-expressing W230X. At 55 degrees C, the mutant protein showed lower thermostability than the wild type protein at pH 3.8 and 7.0. The tertiary structural model of the GALNS protein revealed that aspartic acid at position 60 is located on the surface of the molecule, away from the active site. This makes it unlikely that the enzymatic function of the protein with D60N is severely impaired. On the other hand, A291 and W230 are localized near the active site. The molecular characteristics of the D60N mutation explain the attenuated clinical phenotype of the patients.     

Regulation of TRKB surface expression by brain-derived neurotrophic factor and truncated TRKB isoforms

Brain-derived neurotrophic factor (BDNF) signaling through its receptor TRKB modulates survival, differentiation, and activity of neurons. BDNF activates TRKB on the cell surface, which leads to the initiation of intracellular signaling cascades and different biological responses in neurons. Neuronal activity has been shown to regulate TRKB levels on the plasma membrane of neurons, but little is known about other factors affecting TRKB surface expression levels. We report here that BDNF regulates the cell surface levels of transfected or endogenously expressed full-length TRKB, depending on the exposure time in neuroblastoma cells and primary hippocampal neurons. BDNF rapidly increases TRKB surface expression levels in seconds, whereas treatment of cells with BDNF for a longer time (minutes to hours) leads to decreased TRKB surface levels. Coexpression of the full-length TRKB together with the truncated TRKB.T1 isoform results in decreased levels of full-length TRKB on the cell surface. This effect is specific to the T1 isoform, because coexpression of a kinase-dead TRKB mutant or another kinase domain-lacking TRKB form, truncated T-Shc, leads to increased TRKB surface levels. Our results suggest that regulation of TRKB surface expression levels by different factors is tightly controlled by complex mechanisms in active neurons.