Canine distemper virus persistence in demyelinating encephalitis by swift intracellular cell-to-cell spread in astrocytes is controlled by the viral attachment protein

The mechanism of viral persistence, the driving force behind the chronic progression of inflammatory demyelination in canine distemper virus (CDV) infection, is associated with non-cytolytic viral cell-to-cell spread. Here, we studied the molecular mechanisms of viral spread of a recombinant fluorescent protein-expressing virulent CDV in primary canine astrocyte cultures. Time-lapse video microscopy documented that CDV spread was very efficient using cell processes contacting remote target cells. Strikingly, CDV transmission to remote cells could occur in less than 6 h, suggesting that a complete viral cycle with production of extracellular free particles was not essential in enabling CDV to spread in glial cells. Titration experiments and electron microscopy confirmed a very low CDV particle production despite higher titers of membrane-associated viruses. Interestingly, confocal laser microscopy and lentivirus transduction indicated expression and functionality of the viral fusion machinery, consisting of the viral fusion (F) and attachment (H) glycoproteins, at the cell surface. Importantly, using a single-cycle infectious recombinant H-knockout, H-complemented virus, we demonstrated that H, and thus potentially the viral fusion complex, was necessary to enable CDV spread. Furthermore, since we could not detect CD150/SLAM expression in brain cells, the presence of a yet non-identified glial receptor for CDV was suggested. Altogether, our findings indicate that persistence in CDV infection results from intracellular cell-to-cell transmission requiring the CDV-H protein. Viral transfer, happening selectively at the tip of astrocytic processes, may help the virus to cover long distances in the astroglial network, "outrunning" the host's immune response in demyelinating plaques, thus continuously eliciting new lesions.

Ethanolamine phosphoglycerol attachment to eEF1A is not essential for normal growth of Trypanosoma brucei

Eukaryotic elongation factor 1A (eEF1A) is the only protein modified by ethanolamine phosphoglycerol (EPG). In mammals and plants, EPG is attached to conserved glutamate residues located in eEF1A domains II and III, whereas in the unicellular eukaryote, Trypanosoma brucei, a single EPG moiety is attached to domain III. A biosynthetic precursor of EPG and structural requirements for EPG attachment to T. brucei eEF1A have been reported, but the role of this unique protein modification in cellular growth and eEF1A function has remained elusive. Here we report, for the first time in a eukaryotic cell, a model system to study potential roles of EPG. By down-regulation of EF1A expression and subsequent complementation of eEF1A function using conditionally expressed exogenous eEF1A (mutant) proteins, we show that eEF1A lacking EPG complements trypanosomes deficient in endogenous eEF1A, demonstrating that EPG attachment is not essential for normal growth of T. brucei in culture.

Greek Life and God Attachment: the Interaction of Sorority Influence and Religiosity on Women's Body Shame

The present study investigated the relationships between sorority women’s internalization of Greek thin ideals and body image, and dimensions of sorority women’s religiosity and body image. A combined relationship among sorority women’s internalization of Greek thin ideals, body image, and religiosity was also examined. Based on previous research it was expected that women’s internalization of Greek thin ideals would be associated with worse body image (in terms of body shame, body esteem, and drive for thinness) and that women’s religiosity (in terms of secure attachment to God) would be associated with better body image. Combinations of Greek thin ideal internalization and God attachment were expected to significantly predict changes in women’s body image. Women completed a series of survey measures assessing their awareness and internalization of Greek sociocultural thin ideals and their sense of community within their particular sorority. Women also completed a series of survey measures assessing their body shame, body esteem, and drive for thinness, in addition to survey measures assessing dimensions of their religiosity. The study’s findings revealed that women’s internalization of Greek thin ideals was associated with worse body image outcomes and that anxious attachment to God was associated with worse body image outcomes, particularly in relation to body shame. Moderation analyses revealed that Greek thin ideal internalization significantly interacted with anxious God attachment to predict body shame.

Cementum attachment protein/protein-tyrosine phosphotase-like member A is not expressed in teeth

Cementum is a highly specialized connective tissue that covers tooth roots. The only cementum-specific protein described to date is the cementum attachment protein (CAP). A putative sequence for CAP was established from a cDNA clone isolated from a human cementifying fibroma cDNA library. This sequence overlaps with a phosphatase-like protein in muscle termed the protein-tyrosine phosphatase-like member A (PTPLA). To clarify the nature of CAP/PTPLA, we cloned the homologous rat protein and determined its sequence. The rat protein shared 94% sequence identity with the human protein. On Northern blots containing RNA from various rat tissues of different developmental stages, the cDNA hybridized to an mRNA expressed in heart and skeletal muscle but not in teeth. These results were confirmed by real-time PCR. Thus, the sequence deposited in public databanks under the name 'cementum attachment protein' does not represent genuine CAP.

Structural rearrangements of the central region of the morbillivirus attachment protein stalk domain trigger F protein refolding for membrane fusion

It is unknown how receptor binding by the paramyxovirus attachment proteins (HN, H, or G) triggers the fusion (F) protein to fuse with the plasma membrane for cell entry. H-proteins of the morbillivirus genus consist of a stalk ectodomain supporting a cuboidal head; physiological oligomers consist of non-covalent dimer-of-dimers. We report here the successful engineering of intermolecular disulfide bonds within the central region (residues 91-115) of the morbillivirus H-stalk; a sub-domain that also encompasses the putative F-contacting section (residues 111-118). Remarkably, several intersubunit crosslinks abrogated membrane fusion, but bioactivity was restored under reducing conditions. This phenotype extended equally to H proteins derived from virulent and attenuated morbillivirus strains and was independent of the nature of the contacted receptor. Our data reveal that the morbillivirus H-stalk domain is composed of four tightly-packed subunits. Upon receptor binding, these subunits structurally rearrange, possibly inducing conformational changes within the central region of the stalk, which, in turn, promote fusion. Given that the fundamental architecture appears conserved among paramyxovirus attachment protein stalk domains, we predict that these motions may act as a universal paramyxovirus F-triggering mechanism.

Actor and partner effects of self-esteem on relationship satisfaction and the mediating role of secure attachment between the partners

We examined actor and partner effects of self-esteem on relationship satisfaction, using the actor-partner interdependence model and data from five independent samples of couples. The results indicated that self-esteem predicted the individual’s own relationship satisfaction (i.e., an actor effect) and the relationship satisfaction of his or her partner (i.e., a partner effect), controlling for the effect of the partner’s selfesteem. Gender, age, and length of relationship did not moderate the effect sizes. Moreover, using one of the samples, we tested whether secure attachment to the current partner (assessed as low attachment-related anxiety and avoidance) mediated the effects. The results showed that attachment-related anxiety and avoidance independently mediated both the actor and the partner effect of self-esteem on relationship satisfaction.

Mechanism for active membrane fusion triggering by morbillivirus attachment protein.

The paramyxovirus entry machinery consists of two glycoproteins that tightly cooperate to achieve membrane fusion for cell entry: the tetrameric attachment protein (HN, H, or G, depending on the paramyxovirus genus) and the trimeric fusion protein (F). Here, we explore whether receptor-induced conformational changes within morbillivirus H proteins promote membrane fusion by a mechanism requiring the active destabilization of prefusion F or by the dissociation of prefusion F from intracellularly preformed glycoprotein complexes. To properly probe F conformations, we identified anti-F monoclonal antibodies (MAbs) that recognize conformation-dependent epitopes. Through heat treatment as a surrogate for H-mediated F triggering, we demonstrate with these MAbs that the morbillivirus F trimer contains a sufficiently high inherent activation energy barrier to maintain the metastable prefusion state even in the absence of H. This notion was further validated by exploring the conformational states of destabilized F mutants and stabilized soluble F variants combined with the use of a membrane fusion inhibitor (3g). Taken together, our findings reveal that the morbillivirus H protein must lower the activation energy barrier of metastable prefusion F for fusion triggering.

Who’s to blame? How narcissists and ex-partners of narcissists make sense of romantic breakup

Objective: past research has shown relationship problems associated with narcissists’ excessive self-centeredness and lacking concern for others. Using romantic relationships as opportunities to self-enhance rather than caring about intimacy, narcissists are sensitive to shortcomings in their partners and quick to withdraw investment once relationships turn out to be less than perfect. Our research aimed to reveal whether narcissists are aware of their destructive relationship behavior or tend to put the blame for a failed relationship on their ex-partners. Conversely, do ex-partners of narcissists take the blame and feel responsible for the breakup or walk away convinced their narcissistic ex-partners’ behavior was just too unbearable? Method: 120 participants (19-59 yrs) who reported a recent romantic breakup completed a battery of questionnaires online, including measures of narcissism and self-esteem, as well as newly created scales assessing attributions for breakup. In addition to self-reports, participants retrospectively rated their ex-partners on adapted versions of the same measures. Results: narcissists made attributions to lacking relationship investment mostly in themselves and to a lesser extent in their partners. However, this pattern was reversed when self-esteem was controlled, with attributions to partner shortcomings outnumbering aspects of own destructive behavior. Narcissism perceived in the ex-partner was related to reports of lacking investment in oneself as well as the ex-partner, but controlling for self-esteem reduced the number of attributions to own shortcomings. Conclusion: our analyses revealed that narcissists do show some awareness of their contribution to a failed relationship, although controlling for self-esteem increased their blame of the ex-partner. In contrast, associations between perceived partner-narcissism and aspects of own lacking relationship investment became fewer when self-esteem was controlled for.

Energetics of byssus attachment and feeding in the green-lipped mussel Perna canaliculus.

In most animals, significant increases in metabolic rate are due to activity and to feeding (known as apparent specific dynamic action). We determined the energetic costs of activity and feeding in adult green-lipped mussels (Perna canaliculus). Maximal metabolic rate was determined, using closed-chamber respirometry, during byssus re-attachment, during specific dynamic action after 16 h of feeding with Isochrysis galbana, and for the two activities combined, in 23 mussels. Metabolic rate was significantly elevated above rest by about 1.9-fold during byssus attachment (17.1 ± 1.53 μg O(2) h(-1) g(-1) whole mussel wet weight at rest, increased to 27.9 ± 0.91 μg O(2) h(-1) g(-1)), and by 2.2-fold after feeding (31.4 ± 1.20 μg O(2) h(-1) g(-1)). Combined feeding and byssus attachment led to a still higher metabolic rate (34.0 ± 1.23 μg O(2) h(-1) g(-1)). Behavior was also significantly altered, with mussels being almost continuously open during attachment and after feeding (90%-99% of the time); however, the time spent open during the day decreased, reaching a minimum of 52% ± 9% 3 days after feeding, and remained low (67%-82%) for the following 45-day starvation period. Significant diurnal differences were observed, with mussels continuously (92%-100%) open at night. The key findings from this study are that green-lipped mussels (1) have an aerobic scope of approximately 2-fold; (2) reach a higher metabolic rate during feeding than during activity, and the two combined can raise the metabolic rate higher still; (3) display a marked diurnal behavior.