Does comorbidity matter in body-focused repetitive behavior disorders?

$\textbf{BACKGROUND:}$ Trichotillomania (TTM) and skin-picking disorder (SPD) have been characterized as body-focused repetitive behavior disorders (BFRBs). Because BFRBs frequently co-occur, we sought to discover the similarities and differences for individuals having both TTM and SPD as opposed to 1 of these disorders. $\textbf{METHODS:}$ Participants with primary TTM (N = 421) were evaluated regarding the comorbidity of SPD, and participants with primary SPD (N = 124) were evaluated regarding the comorbidity of TTM. The effects of comorbidity overlap on demographic and clinical measures were evaluated. $\textbf{RESULTS:}$ Of the 421 participants with primary TTM, 61 (14.5%) had co-occurring SPD. Of 124 participants with primary SPD, 21 (16.9%) had comorbid TTM. Participants with primary TTM and comorbid SPD had significantly more severe trichotillomania symptoms and were more likely to have major depressive disorder than those with TTM alone. Participants with primary SPD and comorbid TTM reported significantly more severe skin-picking symptoms than those who had only SPD. $\textbf{CONCLUSIONS:}$ Individuals with co-occurring TTM and SPD may have more problematic symptoms with the primary repetitive behavior. Hair pullers with comorbid SPD were more likely to have comorbid depression. Evaluating patients for multiple BFRBs may be important to assess the severity of symptoms and may have treatment implications.This study was funded by the Trichotillomania Learning Center and its BFRB Precision Medicine Initiative

Brief report: a comparison of the preference for viewing social and non-social movies in typical and autistic adolescents

The recently proposed Social Motivation theory (Chevallier et al., Trends in cognitive sciences 16(4):231–239, 2012) suggests that social difficulties in Autism Spectrum Condition (ASC) might be caused by a difference in the motivation to engage with other people. Here we compared adolescents with (N = 31) and without (N = 37) ASC on the Choose-a-Movie paradigm that measures the social seeking. The results showed a preference for viewing objects over smiling faces in ASC, which is in line with the theory of low social motivation. However, typical adolescents did not show any stimuli preferences, raising questions about developmental changes in social motivation. Age was found to play a significant role in moderating the choice behaviour of the participants. We discuss the implications of these findings in detail

Real-time intermembrane force measurements and imaging of lipid domain morphology during hemifusion

Membrane fusion is the core process in membrane trafficking and is essential for cellular transport of proteins and other biomacromolecules. During protein-mediated membrane fusion, membrane proteins are often excluded from the membrane-membrane contact, indicating that local structural transformations in lipid domains play a major role. However, the rearrangements of lipid domains during fusion have not been thoroughly examined. Here using a newly developed Fluorescence Surface Forces Apparatus (FL-SFA), migration of liquid-disordered clusters and depletion of liquid-ordered domains at the membrane-membrane contact are imaged in real time during hemifusion of model lipid membranes, together with simultaneous force-distance and lipid membrane thickness measurements. The load and contact time-dependent hemifusion results show that the domain rearrangements decrease the energy barrier to fusion, illustrating the significance of dynamic domain transformations in membrane fusion processes. Importantly, the FL-SFA can unambiguously correlate interaction forces and in situ imaging in many dynamic interfacial systems.open0

Mesenchymal Stem Cells Exhibit Firm Adhesion, Crawling, Spreading and Transmigration across Aortic Endothelial Cells: Effects of Chemokines and Shear

Mesenchymal stem cells (MSCs) have anti-inflammatory and immunosuppressive properties and may be useful in the therapy of diseases such as arteriosclerosis. MSCs have some ability to traffic into inflamed tissues, however to exploit this therapeutically their migratory mechanisms need to be elucidated. This study examines the interaction of murine MSCs (mMSCs) with, and their migration across, murine aortic endothelial cells (MAECs), and the effects of chemokines and shear stress. The interaction of mMSCs with MAECs was examined under physiological flow conditions. mMSCs showed lack of interaction with MAECs under continuous flow. However, when the flow was stopped (for 10min) and then started, mMSCs adhered and crawled on the endothelial surface, extending fine microvillous processes (filopodia). They then spread extending pseudopodia in multiple directions. CXCL9 significantly enhanced the percentage of mMSCs adhering, crawling and spreading and shear forces markedly stimulated crawling and spreading. CXCL9, CXCL16, CCL20 and CCL25 significantly enhanced transendothelial migration across MAECs. The transmigrated mMSCs had down-regulated receptors CXCR3, CXCR6, CCR6 and CCR9. This study furthers the knowledge of MSC transendothelial migration and the effects of chemokines and shear stress which is of relevance to inflammatory diseases such as arteriosclerosis

Dimensionality of Carbon Nanomaterials Determines the Binding and Dynamics of Amyloidogenic Peptides: Multiscale Theoretical Simulations

Experimental studies have demonstrated that nanoparticles can affect the rate of protein self-assembly, possibly interfering with the development of protein misfolding diseases such as Alzheimer's, Parkinson's and prion disease caused by aggregation and fibril formation of amyloid-prone proteins. We employ classical molecular dynamics simulations and large-scale density functional theory calculations to investigate the effects of nanomaterials on the structure, dynamics and binding of an amyloidogenic peptide apoC-II(60-70). We show that the binding affinity of this peptide to carbonaceous nanomaterials such as C60, nanotubes and graphene decreases with increasing nanoparticle curvature. Strong binding is facilitated by the large contact area available for π-stacking between the aromatic residues of the peptide and the extended surfaces of graphene and the nanotube. The highly curved fullerene surface exhibits reduced efficiency for π-stacking but promotes increased peptide dynamics. We postulate that the increase in conformational dynamics of the amyloid peptide can be unfavorable for the formation of fibril competent structures. In contrast, extended fibril forming peptide conformations are promoted by the nanotube and graphene surfaces which can provide a template for fibril-growth

Estrus cyclicity of spinogenesis: underlying mechanisms

Hippocampal spine density varies with the estrus cycle. The cyclic change in estradiol levels in serum was hypothesized to underlie this phenomenon, since treatment of ovariectomized animals with estradiol induced an increase in spine density in hippocampal dendrites of rats, as compared to ovariectomized controls. In contrast, application of estradiol to hippocampal slice cultures did not promote spinogenesis. In addressing this discrepancy, we found that hippocampal neurons themselves are capable of synthesizing estradiol de novo. Estradiol synthesis can be suppressed by aromatase inhibitors and by knock-down of Steroid Acute Regulatory Protein (StAR) and enhanced by substrates of steroidogenesis. Expression of estrogen receptors (ERs) and synaptic proteins, synaptogenesis, and long-term potentiation (LTP) correlated positively with aromatase activity in hippocampal cultures without any difference between genders. All effects due to inhibition of aromatase activity were rescued by application of estradiol to the cultures. Most importantly, gonadotropin-releasing hormone (GnRH) increased estradiol synthesis dose-dependently via an aromatase-mediated mechanism and consistently increased spine synapse density and spinophilin expression. As a consequence, our data suggest that cyclic fluctuations in spine synapse density result from pulsative release of GnRH from the hypothalamus and its effect on hippocampal estradiol synthesis, rather than from varying levels of serum estradiol. This hypothesis is further supported by higher GnRH receptor (GnRH-R) density in the hippocampus than in the cortex and hypothalamus and the specificity of estrus cyclicity of spinogenesis in the hippocampus, as compared to the cortex

Single Nucleotide Polymorphisms in IL1B and the Risk of Acute Coronary Syndrome: A Danish Case-Cohort Study

BACKGROUND: Interleukin-1B (IL-1B) is a key pro-inflammatory cytokine that has been associated with the development of atherosclerosis and myocardial infarction. However, the prospective associations between functional single nucleotide polymorphisms (SNPs) in IL1B and incident acute coronary syndrome (ACS) have not been thoroughly investigated. The aims of this study were to examine the associations between individual SNPs in and SNP haplotypes of the promoter region of IL1B and incident ACS in a prospective study. Furthermore, we wanted to explore potential interactions with other risk factors for ACS on an additive scale. METHODOLOGY/PRINCIPAL FINDINGS: The present study was based on the Danish prospective study Diet, Cancer and Health comprising more than 57 000 participants aged 50-64 at baseline. During a median follow-up of 7.2 years we identified 989 cases of incident ACS (755 men and 234 women). All cases were validated by review of medical records, and information on covariates was collected by study technicians. The study was conducted according to a case-cohort study design including ACS cases and a sex-stratified sub cohort of 1663 participants drawn randomly from the entire cohort. Weighted Cox proportional hazard models with age as time axis were used in the statistical analyses. Individual IL1B SNPs, SNP haplotypes, or haplotype combinations were not significantly associated with incident ACS, and, likewise, we found no evidence of interaction on an additive scale between IL1B haplotypes and risk factors, respectively. CONCLUSIONS/SIGNIFICANCE: Genetic variation in the promoter region of IL1B may not be associated with incident ACS in men or women above the age of 50 years

Fibronectin Matrix Assembly Suppresses Dispersal of Glioblastoma Cells

Glioblastoma (GBM), the most aggressive and most common form of primary brain tumor, has a median survival of 12–15 months. Surgical excision, radiation and chemotherapy are rarely curative since tumor cells broadly disperse within the brain. Preventing dispersal could be of therapeutic benefit. Previous studies have reported that increased cell-cell cohesion can markedly reduce invasion by discouraging cell detachment from the tumor mass. We have previously reported that α5β1 integrin-fibronectin interaction is a powerful mediator of indirect cell-cell cohesion and that the process of fibronectin matrix assembly (FNMA) is crucial to establishing strong bonds between cells in 3D tumor-like spheroids. Here, we explore a potential role for FNMA in preventing dispersal of GBM cells from a tumor-like mass. Using a series of GBM-derived cell lines we developed an in vitro assay to measure the dispersal velocity of aggregates on a solid substrate. Despite their similar pathologic grade, aggregates from these lines spread at markedly different rates. Spreading velocity is inversely proportional to capacity for FNMA and restoring FNMA in GBM cells markedly reduces spreading velocity by keeping cells more connected. Blocking FNMA using the 70 KDa fibronectin fragment in FNMA-restored cells rescues spreading velocity, establishing a functional role for FNMA in mediating dispersal. Collectively, the data support a functional causation between restoration of FNMA and decreased dispersal velocity. This is a first demonstration that FNMA can play a suppressive role in GBM dispersal