Molecular diversity and distribution of eastern Atlantic and Mediterranean dogfishes Squalus highlight taxonomic issues in the genus

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record.The alpha taxonomy of the globally distributed shark genus Squalus has been under intense investigation recently, and many new species have been described over the last decade. However, taxonomic uncertainty remains about several taxa. Without consistent nomenclature and the ability to reliably distinguish between the different Squalus species, basic data collection, downstream conservation and management efforts are seriously compromised. To aid in clarifying the taxonomic status of Squalus species in the eastern Atlantic and Mediterranean, we assessed species diversity at the molecular level and evaluated the consistency in species identification in the region. Samples from all nominal Squalus species recognized in the above regions were collected in an international effort and sequenced for regions of the mitochondrial COI and ND2 genes. These data were further analysed alongside publicly available sequences, including 19 of the 26 Squalus species globally recognized, to compare the regional genus-level diversity with that found elsewhere. Our results confirm inconsistent species identification in the eastern Atlantic and Mediterranean Squalus, particularly concerning S. blainville and S. megalops, and reinforce the need to revise the status of S. megalops and S. mitsukurii as they may include several distinct species distributed around the world. The status of S. blainville is also discussed in the light of the current findings and its problematic taxonomic history.Systematic Research Fund. Fundação para a Ciência e Tecnologia. Grant Number: SFRH/BPD/77487/2007. Social European Fund. Portuguese funds. New Zealand National Institute of Water and Atmospheric Research Lt

RGDS peptides immobilized on titanium alloy stimulate bone cell attachment, differentiation and confer resistance to apoptosis

A major cause of implant failure in skeletal tissues is failure of osseointegration, often due to lack of adhesion of cells to the titanium (Ti) alloy interface. Since arginine- glycine-aspartic acid (RGD)-containing peptides have been shown to regulate osteoblast adhesion, we tested the hypothesis that, bound to a Ti surface, these peptides would promote osteoblasts differentiation, while at the same time inhibit apoptosis. RGDS and RGES (control) peptides were covalently linked to Ti discs using an APTS linker. While the grafting of both RGDS and RGES significantly increased Ti surface roughness, contact angle analysis showed that APTS significantly increased the surface hydrophobicity; when the peptides were tethered to Ti, this was reduced. To evaluate attachment, MC3T3-E1 osteoblast cells were grown on these discs. Significantly more cells attached to the Ti-grafted RGDS then the Ti-grafted RGES control. Furthermore, expression of the osteoblasts phenotype was significantly enhanced on the Ti-grafted RGDS surface. When cells attached to the Ti-grafted RGDS were challenged with staurosporine, an apoptogen, there was significant inhibition of apoptosis; in contrast, osteoblasts adherent to the Ti-grafted RGES were killed. It is concluded that RGD-containing peptides covalently bonded to Ti promotes osteoblasts attachment and survival with minimal changes to the surface of the alloy. Therefore, such modifications to Ti would have the potential to promote osseointegration in vivo

Nine Months of Hybrid Intradialytic Exercise Training Improves Ejection Fraction and Cardiac Autonomic Nervous System Activity.

Cardiovascular disease is the most common cause of death in hemodialysis (HD) patients. Intradialytic aerobic exercise training has a beneficial effect on cardiovascular system function and reduces mortality in HD patients. However, the impact of other forms of exercise on the cardiovascular system, such as hybrid exercise, is not clear. Briefly, hybrid exercise combines aerobic and strength training in the same session. The present study examined whether hybrid intradialytic exercise has long-term benefits on left ventricular function and structure and the autonomous nervous system in HD patients. In this single-group design, efficacy-based intervention, twelve stable HD patients (10M/2F, 56 ± 19 years) participated in a nine-month-long hybrid intradialytic training program. Both echocardiographic assessments of left ventricular function and structure and heart rate variability (HRV) were assessed pre, during and after the end of the HD session at baseline and after the nine-month intervention. Ejection Fraction (EF), both assessed before and at the end of the HD session, appeared to be significantly improved after the intervention period compared to the baseline values (48.7 ± 11.1 vs. 58.8 ± 6.5, p = 0.046 and 50.0 ± 13.4 vs. 56.1 ± 3.4, p = 0.054 respectively). Regarding HRV assessment, hybrid exercise training increased LF and decreased HF (p p > 0.05). In conclusion, long-term intradialytic hybrid exercise training was an effective non-pharmacological approach to improving EF and the cardiac autonomous nervous system in HD patients. Such exercise training programs could be incorporated into HD units to improve the patients' cardiovascular health

Topography and relationship-specific social touching in individuals displaying body image disturbances

Interpersonal touch is intimately related to the emotional bond between the touch giver and the touch receiver. Which bodily regions we touch in those individuals in our social network is relationship specific. Perception of interpersonal touch is altered in psychiatric disorders characterised by body image disturbances (BIDs). Here, we examined whether the ‘imagined’ experience of social touch in individuals with BIDs is body topography- and relationship-specific. By using an interactive media mobile App, the Virtual Touch Toolkit, high versus low levels of BIDs participants completed heatmaps of full-body virtual avatars, to indicate the body regions they find soothing/unpleasant to be touched by a loved one versus an acquaintance. Self-reports of interoceptive awareness and dysmorphic concerns were also measured. Overall, imagined touch was rated as the most soothing when received from a loved one, and also when this was delivered to ‘social’ body regions. The importance of the social relationship for the imagined tactile interactions was particularly evident for the high levels of BIDs group, with greater problems with interoceptive awareness predicting higher soothing touch ratings when this was received by a loved one. Despite the evidence that imagined bodily contacts between meaningful people is the most pleasant for socially acceptable bodily regions, our findings may suggest a greater sensitivity to relation-specific bodily patterns of social touch particularly in the high level of BIDs group. Heightened interoceptive awareness may also play a key role in this experience of bodily affective contacts. Future research for body-oriented therapy for BIDs is encouraged to systematically probe the efficacy of imagined social touch interaction protocols which use more plausible, ecological, scenarios where touch is delivered by loved ones and to socially acceptable bodily regions

Combined ChIP-Seq and transcriptome analysis identifies AP-1/JunD as a primary regulator of oxidative stress and IL-1β synthesis in macrophages

10.1186/1471-2164-14-92BMC Genomics1419

A tale of two seas: contrasting patterns of population structure in the small-spotted catshark across Europe.

Elasmobranchs represent important components of marine ecosystems, but they can be vulnerable to overexploitation. This has driven investigations into the population genetic structure of large-bodied pelagic sharks, but relatively little is known of population structure in smaller demersal taxa, which are perhaps more representative of the biodiversity of the group. This study explores spatial population genetic structure of the small-spotted catshark (Scyliorhinus canicula), across European seas. The results show significant genetic differences among most of the Mediterranean sample collections, but no significant structure among Atlantic shelf areas. The data suggest the Mediterranean populations are likely to have persisted in a stable and structured environment during Pleistocene sea-level changes. Conversely, the Northeast Atlantic populations would have experienced major changes in habitat availability during glacial cycles, driving patterns of population reduction and expansion. The data also provide evidence of male-biased dispersal and female philopatry over large spatial scales, implying complex sex-determined differences in the behaviour of elasmobranchs. On the basis of this evidence, we suggest that patterns of connectivity are determined by trends of past habitat stability that provides opportunity for local adaptation in species exhibiting philopatric behaviour, implying that resilience of populations to fisheries and other stressors may differ across the range of species

Reciprocal co-regulation of EGR2 and MECP2 is disrupted in Rett syndrome and autism

Mutations in MECP2, encoding methyl-CpG-binding protein 2 (MeCP2), cause the neurodevelopmental disorder Rett syndrome (RTT). Although MECP2 mutations are rare in idiopathic autism, reduced MeCP2 levels are common in autism cortex. MeCP2 is critical for postnatal neuronal maturation and a modulator of activity-dependent genes such as Bdnf (brain-derived neurotropic factor) and JUNB. The activity-dependent early growth response gene 2 (EGR2), required for both early hindbrain development and mature neuronal function, has predicted binding sites in the promoters of several neurologically relevant genes including MECP2. Conversely, MeCP2 family members MBD1, MBD2 and MBD4 bind a methylated CpG island in an enhancer region located in EGR2 intron 1. This study was designed to test the hypothesis that MECP2 and EGR2 regulate each other’s expression during neuronal maturation in postnatal brain development. Chromatin immunoprecipitation analysis showed EGR2 binding to the MECP2 promoter and MeCP2 binding to the enhancer region in EGR2 intron 1. Reduction in EGR2 and MeCP2 levels in cultured human neuroblastoma cells by RNA interference reciprocally reduced expression of both EGR2 and MECP2 and their protein products. Consistent with a role of MeCP2 in enhancing EGR2, Mecp2-deficient mouse cortex samples showed significantly reduced EGR2 by quantitative immunofluorescence. Furthermore, MeCP2 and EGR2 show coordinately increased levels during postnatal development of both mouse and human cortex. In contrast to age-matched Controls, RTT and autism postmortem cortex samples showed significant reduction in EGR2. Together, these data support a role of dysregulation of an activity-dependent EGR2/MeCP2 pathway in RTT and autism

Expression and prognostic relevance of activated extracellular-regulated kinases (ERK1/2) in breast cancer

Extracellular-regulated kinases (ERK1, ERK2) play important roles in the malignant behaviour of breast cancer cells in vitro. In our present study, 148 clinical breast cancer samples (120 cases with follow-up data) were studied for the expression of ERK1, ERK2 and their phosphorylated forms p-ERK1 and p-ERK2 by immunoblotting, and p-ERK1/2 expression in corresponding paraffin sections was analysed by immunohistochemistry. The results were correlated with established clinical and histological prognostic parameters, follow-up data and expression of seven cell-cycle regulatory proteins as well as MMP1, MMP9, PAI-1 and AP-1 transcription factors, which had been analysed before. High p-ERK1 expression as determined by immunoblots correlated significantly with a low frequency of recurrences and infrequent fatal outcome (P=0.007 and 0.008) and was an independent indicator of long relapse-free and overall survival in multivariate analysis. By immunohistochemistry, strong p-ERK staining in tumour cells was associated with early stages (P=0.020), negative nodal status (P=0.003) and long recurrence-free survival (P=0.017). In contrast, expression of the unphosphorylated kinases ERK1 and ERK2 was not associated with clinical and histological prognostic parameters, except a positive correlation with oestrogen receptor status. Comparison with the expression of formerly analysed cell-cycle- and invasion-associated proteins corroborates our conclusion that activation of ERK1 and ERK2 is not associated with enhanced proliferation and invasion of mammary carcinomas