UCSF Journal Club
Recent Research by UCSF Scientists
Alexandra Greer
Science Editor
IMMUNOLOGY: Regulation of T cell priming by lymphoid stroma. Khan, O. et al., (Krummel). PLoS One. 6(11):e26138.
In the lymph node, naïve T-cells become activated through interaction with activated dendritic cells (DCs). Activated DCs provide multiple signals to the T-cells, including direct stimulation via MHC:T-cell receptor interactions and costimulatory molecules, and indirect signals via DC cytokine release. In this sense, the setting of the lymph node (the stromal environment) is overlooked as a source for immune regulation and has been considered more of an inert setting for these interactions to take place. However, researchers recently found that stromal cells release factors that can significantly influence the proliferation of recently activated T-cells. Lymph node fibroblastic reticular cells were found to release inducible nitric oxide synthase (iNOS) in response to IFNy production by the recently activated T-cells, which resulted in reduced T-cell proliferation and T-cell clustering. Therefore, the authors conclude that this represents an important method of feedback inhibition by stromal cells early in T-cell activation.
NEUROSCIENCE: Organized representation of spectrotemporal features in songbird auditory forebrain. Kim, G.; Doupe, A. Journal of Neuroscience. 31(47):16977-90.
It is unknown how the mammalian brain spatially organizes different types of auditory cues. For example: are sounds with different pitches recognized in distinct parts of the brain? To study this, songbirds are a particularly useful model animal because of their complicated, speech-like vocalizations and their ability to learn. In this study, researchers attached electrodes to the brains of zebra finches while they listened to different complex tones and recorded the resulting brain activity. They found specific spatial organization of sounds both by their tone and their duration in a part of the brain that correlates with auditory processing in mammals. Given how little is known about the spatial organization of auditory processing in mammals, this study provides some support for the hypothesis that mammals may have similar organization of auditory processing.
MICROBIOLOGY: SRE1 regulates Iron-dependent and independent pathways in the fungal pathogen Histoplasma capsulatum. Hwang, L.H.; Seth, E.; Gilmore, S.A.; Sil, A. Eukaryotic Cell. Nov 23. [Epub ahead of print]
Histoplasma capsulatum is a fungal, sometimes opportunistic, pathogen that colonizes the lungs and causes histoplasmosis, characterized by respiratory symptoms that can become systemic and fatal if untreated. Like many other pathogens, Histoplasma must regulate its iron carefully to survive inside of its host. For example, host cells restrict the availability of iron as a response to infection, which could result in the pathogen’s death unless it can carefully regulate its use and acquisition of iron. In this paper, researchers have identified SRE1 as a critical transcription factor required for proper regulation of iron in a variety of environments. Depletion of SRE1 transcript with RNA interference resulted in the inability to recognize iron-rich environments or iron-poor environments, resulting in the misregulation of multiple iron response genes. Furthermore, they found that in addition to iron regulation, SRE1 misregulation resulted in changes in cell morphology, indicating that SRE1 regulation of target genes is required for both iron response and other iron-independent pathways.
SURGERY: Critical role of activated Protein C (aPC) in early coagulopathy and later organ failure, infection and death in trauma patients. Cohen, M.J. et al. (Pittet). Annals of Surgery. Nov 30. [Epub ahead of print]
Plasma protein C (or simply Protein C) is a protein critical for the regulation of blood clots, inflammation, and vascular permeability. When activated (then called aPC), it inhibits the formation of blood clots by cleaving and inactivating Factors Va and VIIIa, which both promote blood coagulation. Therefore, too much circulating aPC can result in coagulopathy, or the relative inability of blood to clot (resulting in blood loss). Here, researchers investigated the role of aPC in coagulopathy of trauma patients. In what they describe as a maladaptive response to trauma, the body increases circulating aPC levels, resulting in an inability to form blood clots. In a hospital setting, this can result in uncontrollable blood loss and severe complications, including infection, organ dysfunction, and even death. While many previous studies considered hospital interventions to be the cause of this common coagulopathy, these researchers have identified this biological response to trauma as a likely contributor.
Alexandra Greer is a fourth-year biomedical sciences student.
This article appeared in the December 8, 2011 issue of Synapse.