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Extracellular vesicles are thought to facilitate pathogen transmission from arthropods to humans and other animals. Here, we reveal that pathogen spreading from arthropods to the mammalian host is multifaceted. Extracellular vesicles from Ixodes scapularis enable tick feeding and promote infection of the mildly virulent rickettsial agent Anaplasma phagocytophilum through the SNARE proteins Vamp33 and Synaptobrevin 2 and dendritic epidermal T cells. However, extracellular vesicles from the tick Dermacentor andersoni mitigate microbial spreading caused by the lethal pathogen Francisella tularensis. Collectively, we establish that tick extracellular vesicles foster distinct outcomes of bacterial infection and assist in vector feeding by acting on skin immunity. Thus, the biology of arthropods should be taken into consideration when developing strategies to control vector-borne diseases. Extracellular vesicles have been implicated in the transmission of pathogens from the arthropod to the human host. Here the authors show that tick-derived extracellular vesicles play a role in feeding and modulate the outcome of bacterial infection. [ABSTRACT FROM AUTHOR]

The E3 ubiquitin ligase X-linked inhibitor of apoptosis (XIAP) acts as a molecular rheostat for the immune deficiency (IMD) pathway of the tick Ixodes scapularis. How XIAP activates the IMD pathway in response to microbial infection remains ill defined. Here, we identified the XIAP enzymatic substrate p47 as a positive regulator of the I. scapularis IMD network. XIAP polyubiquitylates p47 in a lysine 63-dependent manner and interacts with the p47 ubiquitin-like (UBX) module. p47 also binds to Kenny (IKKγ/NEMO), the regulatory subunit of the inhibitor of nuclear factor (NF)- κB kinase complex. Replacement of the amino acid lysine to arginine within the p47 linker region completely abrogated molecular interactions with Kenny. Furthermore, mitigation of p47 transcription levels through RNA interference in I. scapularis limited Kenny accumulation, reduced phosphorylation of IKKβ (IRD5), and impaired cleavage of the NF-κB molecule Relish. Accordingly, disruption of p47 expression increased microbial colonization by the Lyme disease spirochete Borrelia burgdorferi and the rickettsial agent Anaplasma phagocytophilum. Collectively, we highlight the importance of ticks for the elucidation of paradigms in arthropod immunology. Manipulating immune signaling cascades within I. scapularis may lead to innovative approaches to reducing the burden of tick-borne diseases. [ABSTRACT FROM AUTHOR]

Background. Many changes in social behavior take place during adolescence. Sexuality and romantic interests emerge during this time, and adolescents spend more time with peers and less time with parents and family. While such changes in social behavior have been well documented in the literature, relatively few neurophysiological explanations for these behavioral changes have been presented.Method. In this article we selectively review studies documenting (a) the neuronal circuits that are dedicated to the processing of social information; (b) the changes in social behavior that take place during adolescence; (c) developmental alterations in the adolescent brain; and (d) links between the emergence of mood and anxiety disorders in adolescence and changes in brain physiology occurring at that time.Results. The convergence of evidence from this review indicates a relationship between development of brain physiology and developmental changes in social behavior. Specifically, the surge of gonadal steroids at puberty induces changes within the limbic system that alters the emotional attributions applied to social stimuli while the gradual maturation of the prefrontal cortex enables increasingly complex and controlled responses to social information.Conclusions. Observed alterations in adolescent social behavior reflect developmental changes in the brain social information processing network. We further speculate that dysregulation of the social information processing network in this critical period may contribute to the onset of mood and anxiety disorders during adolescence. [ABSTRACT FROM AUTHOR]

Little is understood about the brain basis of anxiety, particularly among youth. However, threat paradigms with animals are delineating the relationship between anxietylike behaviors and brain function. We adapted a threat paradigm for adolescents using functional magnetic resonance imaging. The aim was to examine amygdala activation to fear. The threat was an aversive air blast directed to the larynx. Participants were explicitly informed that they might receive the air blast when viewing one stimulus (threat condition) and would not receive the blast when viewing the other stimulus (safe condition). Participants provided fear ratings immediately after each trial. Based on the relatively mild nature of the air blast, we expected participants to report varying degrees of fear. Those who reported increased fear showed right amygdala activation during the threat condition and left amygdala activation in the safe condition. These procedures offer a promising tool for studying youth with anxiety disorders. © 2003 Wiley Periodicals, Inc. Dev Psychobiol 43: 359–366, 2003. [ABSTRACT FROM AUTHOR]