Essential roles for the Tec family kinases Tec and Btk in M-CSF receptor signaling pathways that regulate macrophage survival

Tec family kinases have important roles in lymphocytes; however, little is known about their function in monocytes/macrophages. In this study we report that Tec family kinases are essential for M-CSF (M-CSF)-induced signaling pathways that regulate macrophage survival. Compared with wild-type bone marrow-derived macrophage (BMM) cultures, Tec(-/-)Btk(-/-) BMM cultures displayed increased cell death that correlated with a severe drop in macrophage numbers. In addition, macrophages deficient in either Tec or Btk showed expression and activation of caspase-11. Elucidation of M-CSF receptor (M-CSFR) signaling pathways revealed that the total tyrosine phosphorylation pattern upon M-CSF stimulation was altered in Tec(-/-)Btk(-/-) macrophages despite normal expression and phosphorylation of the M-CSFR. Further, Tec and Btk are required for proper expression of the GM-CSF receptor alpha (GM-CSFRalpha) chain in macrophages but not dendritic cells, implicating Tec family kinases in the lineage-specific regulation of GM-CSFRalpha expression. Taken together, our study shows that Tec and Btk regulate M-CSFR signaling-induced macrophage survival and provides a novel link between Tec family kinases and the regulation of caspase-11 and GM-CSFRalpha expression.     

Dissociable influences of auditory object vs. spatial attention on visual system oscillatory activity

Given that both auditory and visual systems have anatomically separate object identification ("what") and spatial ("where") pathways, it is of interest whether attention-driven cross-sensory modulations occur separately within these feature domains. Here, we investigated how auditory "what" vs. "where" attention tasks modulate activity in visual pathways using cortically constrained source estimates of magnetoencephalograpic (MEG) oscillatory activity. In the absence of visual stimuli or tasks, subjects were presented with a sequence of auditory-stimulus pairs and instructed to selectively attend to phonetic ("what") vs. spatial ("where") aspects of these sounds, or to listen passively. To investigate sustained modulatory effects, oscillatory power was estimated from time periods between sound-pair presentations. In comparison to attention to sound locations, phonetic auditory attention was associated with stronger alpha (7-13 Hz) power in several visual areas (primary visual cortex; lingual, fusiform, and inferior temporal gyri, lateral occipital cortex), as well as in higher-order visual/multisensory areas including lateral/medial parietal and retrosplenial cortices. Region-of-interest (ROI) analyses of dynamic changes, from which the sustained effects had been removed, suggested further power increases during Attend Phoneme vs. Location centered at the alpha range 400-600 ms after the onset of second sound of each stimulus pair. These results suggest distinct modulations of visual system oscillatory activity during auditory attention to sound object identity ("what") vs. sound location ("where"). The alpha modulations could be interpreted to reflect enhanced crossmodal inhibition of feature-specific visual pathways and adjacent audiovisual association areas during "what" vs. "where" auditory attention.     

An empirical test of a diffusion model: predicting clouded apollo movements in a novel environment

Functional connectivity is a fundamental concept in conservation biology because it sets the level of migration and gene flow among local populations. However, functional connectivity is difficult to measure, largely because it is hard to acquire and analyze movement data from heterogeneous landscapes. Here we apply a Bayesian state-space framework to parameterize a diffusion-based movement model using capture-recapture data on the endangered clouded apollo butterfly. We test whether the model is able to disentangle the inherent movement behavior of the species from landscape structure and sampling artifacts, which is a necessity if the model is to be used to examine how movements depend on landscape structure. We show that this is the case by demonstrating that the model, parameterized with data from a reference landscape, correctly predicts movements in a structurally different landscape. In particular, the model helps to explain why a movement corridor that was constructed as a management measure failed to increase movement among local populations. We illustrate how the parameterized model can be used to derive biologically relevant measures of functional connectivity, thus linking movement data with models of spatial population dynamics.     

Bmx tyrosine kinase transgene induces skin hyperplasia, inflammatory angiogenesis, and accelerated wound healing

The Bmx gene, a member of the Tec family of nonreceptor protein tyrosine kinases, is expressed in arterial endothelium and in certain hematopoietic and epithelial cells. Previous in vitro studies have implicated Bmx signaling in cell migration and survival and suggested that it contributes to the progression of prostate carcinomas. However, the function of Bmx in normal tissues in vivo is unknown. We show here that Bmx expression is induced in skin keratinocytes during wound healing. To analyze the role of Bmx in epidermal keratinocytes in vivo, we generated transgenic mice overexpressing Bmx in the skin. We show that Bmx overexpression accelerates keratinocyte proliferation and wound reepithelialization. Bmx expression also induces chronic inflammation and angiogenesis in the skin, and gene expression profiling suggests that this occurs via cytokine-mediated recruitment of inflammatory cells. Our studies provide the first data on Bmx function in vivo and form the basis of evaluation of its role in epithelial neoplasia.