Retrograde transport pathways utilised by viruses and protein toxins

A model has been presented for retrograde transport of certain toxins and viruses from the cell surface to the ER that suggests an obligatory interaction with a glycolipid receptor at the cell surface. Here we review studies on the ER trafficking cholera toxin, Shiga and Shiga-like toxins, Pseudomonas exotoxin A and ricin, and compare the retrograde routes followed by these protein toxins to those of the ER trafficking SV40 and polyoma viruses. We conclude that there is in fact no obligatory requirement for a glycolipid receptor, nor even with a protein receptor in a lipid-rich environment. Emerging data suggests instead that there is no common pathway utilised for retrograde transport by all of these pathogens, the choice of route being determined by the particular receptor utilised

Effects of Flight on Gene Expression and Aging in the Honey Bee Brain and Flight Muscle

Honey bees move through a series of in-hive tasks (e.g., “nursing”) to outside tasks (e.g., “foraging”) that are coincident with physiological changes and higher levels of metabolic activity. Social context can cause worker bees to speed up or slow down this process, and foragers may revert back to their earlier in-hive tasks accompanied by reversion to earlier physiological states. To investigate the effects of flight, behavioral state and age on gene expression, we used whole-genome microarrays and real-time PCR. Brain tissue and flight muscle exhibited different patterns of expression during behavioral transitions, with expression patterns in the brain reflecting both age and behavior, and expression patterns in flight muscle being primarily determined by age. Our data suggest that the transition from behaviors requiring little to no flight (nursing) to those requiring prolonged flight bouts (foraging), rather than the amount of previous flight per se, has a major effect on gene expression. Following behavioral reversion there was a partial reversion in gene expression but some aspects of forager expression patterns, such as those for genes involved in immune function, remained. Combined with our real-time PCR data, these data suggest an epigenetic control and energy balance role in honey bee functional senescence

Exploring the Relationship Between Universal-Diverse Orientation and Personality

This study examined the relationship between universal-diverse orientation (UDO), a relatively new concept associated with multicultural awareness that is related to the recognition and acceptance of both similarities and differences among people (Miville et al., 1999), and personality. Participants were one hundred and one college students who completed a measure of UDO, the Miville-Guzman Universality-Diversity Scale (M-GUDS; Miville et al., 1999), and a well-established measure of normal personality, the California Psychological Inventory (CPI; Gough, 1987). Researchers hypothesized that significant relationships would exist between UDO and healthy attributes of personality. Initial results supported this hypothesis; however, post hoc analyses indicated that the demographic variables age and education were also significantly correlated with UDO, and these appear to moderate the relationship between UDO personality. Practical applications and implications for future research are offered. Vontress (1988, 1996) suggested that via the confluence of five cultures (i.e., universal, ecological, national, regional, racioethnic), human development produces includes idiographic differences as well as communal traits that transcend individual differences. Vontress went on to propose that an awareness of and appreciation for the differences and commonalities between and among cultures is important for effective human interaction. Miville et al. (1999) put a finer point on this idea. They believe that attentiveness toward and acceptance of group differences is critical for those who work with diverse persons from a variety of social-cultural backgrounds. Influenced by this Vontress, Miville et al. introduced the universal-diverse orientation (UDO) as ―an attitude toward all other persons that is inclusive yet differentiating in that similarities and differences are both recognized and accepted; the shared experience of being human results in a sense of connectedness with people and is associated with a plurality or diversity of interactions with others‖ (p. 292). Miville et al. (1999) reported that UDO is theoretically associated with personality functioning and wellness. Initial evidence has surfaced to support this link. For example, preliminary data indicate that UDO is related to attentiveness and responsiveness to others, openness to new experiences, interest and commitment to social and cultural activities of diverse people, and the ability to appreciate the impact of one\u27s own and others\u27 diversity (Constantine, et al., 2001; Thompson, Brossart, Carlozzi, & Miville, 2002; Yeh & Arora, 2003). Further, Miville et al. (1999) reported links between UDO and personality variables such as attitudes towards gender, well-being, mental health, autonomy, independence, and empathy--features that seem to be central to effectiveness in social interaction, such as is needed among counselors. Additionally, the UDO was negatively related to ratings of homophobia and dogmatism. Later, Strauss and Connerley (2003) and Thompson et al. (2002) added to the investigation of this hypothesized link. Strauss and Connerley found that the personality variables agreeableness (selflessness, tolerance, helpfulness) and openness to experience were positively and significantly associated with UDO. Thompson et al. also reported that UDO was linked to openness to experience. Together, these studies provide initial support for the Miville et al personality and UDO hypotheses. However, these studies used narrowly defined personality variables. Therefore, additional research is needed to expand and develops the UDO literature base. Because the UDO provides a framework for understanding and appreciating the foundational similarities and differences central to effective multicultural counseling, additional research is needed to evaluate this important construct. Therefore, the purpose of this paper is to build upon and extend the research investigating the theorized relationship between UDO and personality. Specifically, we will examine the relationship between UDO, as measured by the Miville-Guzman Universality-Diversity Scale (M-GUDS; Miville et al., 1999) and selected variables from a well-established measure of personality traits, the California Personality Inventory (Gough, 1996) in a sample of students enrolled in courses offered in two university departments: counseling and mental health services, and psychology

Genome-wide identification of FoxO-dependent gene networks in skeletal muscle during C26 cancer cachexia

BACKGROUND: Evidence from cachectic cancer patients and animal models of cancer cachexia supports the involvement of Forkhead box O (FoxO) transcription factors in driving cancer-induced skeletal muscle wasting. However, the genome-wide gene networks and associated biological processes regulated by FoxO during cancer cachexia are unknown. We hypothesize that FoxO is a central upstream regulator of diverse gene networks in skeletal muscle during cancer that may act coordinately to promote the wasting phenotype. METHODS: To inhibit endogenous FoxO DNA-binding, we transduced limb and diaphragm muscles of mice with AAV9 containing the cDNA for a dominant negative (d.n.) FoxO protein (or GFP control). The d.n.FoxO construct consists of only the FoxO3a DNA-binding domain that is highly homologous to that of FoxO1 and FoxO4, and which outcompetes and blocks endogenous FoxO DNA binding. Mice were subsequently inoculated with Colon-26 (C26) cells and muscles harvested 26 days later. RESULTS: Blocking FoxO prevented C26-induced muscle fiber atrophy of both locomotor muscles and the diaphragm and significantly spared force deficits. This sparing of muscle size and function was associated with the differential regulation of 543 transcripts (out of 2,093) which changed in response to C26. Bioinformatics analysis of upregulated gene transcripts that required FoxO revealed enrichment of the proteasome, AP-1 and IL-6 pathways, and included several atrophy-related transcription factors, including Stat3, Fos, and Cebpb. FoxO was also necessary for the cancer-induced downregulation of several gene transcripts that were enriched for extracellular matrix and sarcomere protein-encoding genes. We validated these findings in limb muscles and the diaphragm through qRT-PCR, and further demonstrate that FoxO1 and/or FoxO3a are sufficient to increase Stat3, Fos, Cebpb, and the C/EBPβ target gene, Ubr2. Analysis of the Cebpb proximal promoter revealed two bona fide FoxO binding elements, which we further establish are necessary for Cebpb promoter activation in response to IL-6, a predominant cytokine in the C26 cancer model. CONCLUSIONS: These findings provide new evidence that FoxO-dependent transcription is a central node controlling diverse gene networks in skeletal muscle during cancer cachexia, and identifies novel candidate genes and networks for further investigation as causative factors in cancer-induced wasting.R01 AR060217 - NIAMS NIH HHS; R01 AR060209 - NIAMS NIH HHS; T32 HD043730 - NICHD NIH HHS; R00 HL098453 - NHLBI NIH HHS; R00HL098453 - NHLBI NIH HHS; R01AR060209 - NIAMS NIH HHS; R01AR060217 - NIAMS NIH HH

The genome and proteome of coliphage T1

AbstractThe genome of enterobacterial phage T1 has been sequenced, revealing that its 50.7-kb terminally redundant, circularly permuted sequence contains 48,836 bp of nonredundant nucleotides. Seventy-seven open reading frames (ORFs) were identified, with a high percentage of small genes located at the termini of the genomes displaying no homology to existing phage or prophage proteins. Of the genes showing homologs (47%), we identified those involved in host DNA degradation (three endonucleases) and T1 replication (DNA helicase, primase, and single-stranded DNA-binding proteins) and recombination (RecE and Erf homologs). While the tail genes showed homology to those from temperate coliphage N15, the capsid biosynthetic genes were unique. Phage proteins were resolved by 2D gel electrophoresis, and mass spectrometry was used to identify several of the spots including the major head, portal, and tail proteins, thus verifying the annotation

Listening to limericks: a pupillometry investigation of perceivers’ expectancy

What features of a poem make it captivating, and which cognitive mechanisms are sensitive to these features? We addressed these questions experimentally by measuring pupillary responses of 40 participants who listened to a series of Limericks. The Limericks ended with either a semantic, syntactic, rhyme or metric violation. Compared to a control condition without violations, only the rhyme violation condition induced a reliable pupillary response. An anomaly-rating study on the same stimuli showed that all violations were reliably detectable relative to the control condition, but the anomaly induced by rhyme violations was perceived as most severe. Together, our data suggest that rhyme violations in Limericks may induce an emotional response beyond mere anomaly detection