UCSF Journal Club: Recent research by UCSF scientists
Alexandra Greer
Science Editor
NEUROSCIENCE: Similar Neural Activity during Fear and Disgust in the Rat Basolateral Amygdala. Shabel, S.J.; Schairer, W.; Donahue, R.J.; Powell, V.; Janak, P.H. PLoS One. 6(12):e27797.
In psychology, the term ‘valence’ refers to the attractiveness or unattractiveness of a particular feeling: happiness and joy would have positive valences, while fear and disgust would have negative valences. In this paper, researchers investigated the similarities in neural activity for emotions with similar affective valences – fear and disgust – as compared to feelings with very different valences. Researchers focused on an area of the brain known to be involved in fear processing: the basolateral amygdala (BLA) by implanting rats with electrode arrays that record neuronal activity in the BLA. They then induced fear with a mild foot shock followed by either disgust (salt- or sugar-water with a bad flavor) or reward (plain salt- or sugar-water). In line with their hypothesis, they found that neuronal activity was more similar between the fear and disgust compared to fear and reward patterns.
CELL BIOLOGY: Axin pathway activity regulates in vivo pY654-β-catenin accumulation and pulmonary fibrosis. Ulsamer, A. et al., (Chapman). Journal of Biological Chemistry. Dec 27. [Epub ahead of print]
Pulmonary fibrosis is a chronic, progressive lung disease that involves the development of excess fibrotic tissue in the lung, leading to shortness of breath, coughing, and weakness. Because the scarring is irreversible, treatment options are very limited and are essentially restricted to lung transplantation for severe cases. Accumulation of certain types of β-catenin has been implicated in the development of pulmonary fibrosis but its role is not completely understood. Here, researchers demonstrated that treatment of fibrotic mice with a tankyrase inhibitor increased survival and increased axin levels, resulting in decreased (pY654) β-catenin levels and decreased accumulation of harmful collagen in the lung. This paper therefore solidifies the role of β-catenin pY654 in promoting the development of pulmonary fibrosis and suggests that the regulation of axin levels may be a potential therapeutic for this disease.
DEVELOPMENTAL BIOLOGY: Ror2 enhances polarity and directional migration of primordial germ cells. Laird, D.J.; Altshuler-Keylin, S.; Kissner, M.D.; Zhou, X.; Anderson, K.V. PLoS Genetics. 7(12):e1002428.
Primordial germ cells are the stem cells that form our gametes; in women, these cells will become eggs and in men, these cells will become sperm. In the developing embryo, these primordial germ cells must travel to the just-developing gonads. During this travel, the germ cells elongate and develop a cellular polarity, which until recently has not been well understood. Here, researchers have identified a receptor tyrosine-kinase-like protein called Ror2 which is found asymmetrically on migrating primordial germ cells and is necessary for their proper migration. In normal primordial germ cells, elongation and migration are a response to the secreted stem cell factor (SCF), but this response is lost in Ror2 mutant cells, indicating that Ror2 uses SCF to induce migration to the nascent gonads.
CANCER BIOLOGY: An experimental xenograft mouse model of diffuse pontine glioma designed for therapeutic testing. Aoki, Y. et al. (Gupta). Journal of Neurooncology. Jan 10. [Epub ahead of print]
Diffuse pontine gliomas are a brain cancer found predominantly in children that involve multiple tumors located in the pons of the brainstem and have a poor prognosis, with a minority of patients surviving even 2 years post-diagnosis. In vivo research on this type of cancer has been difficult, but this lab previously developed a rat model of diffuse pontine glioma using isolated tumor cells from a glioma patient grafted onto an athymic rat. In this paper, the researchers have developed a better model using athymic mice and the same human tumor cells. With this improved model, they were able to show increased survival with temozolomide treatment, indicating that this mouse model is an effective model of glioma disease course and potential treatment.
Alexandra Greer is a fourth-year biomedical sciences student.
This article appeared in the January 19, 2012 issue of Synapse.