Faculty Bibliography

BACKGROUND: The papillary muscles (PMs) play an important role in normal cardiac function, helping to prevent leakage through the AV valves during systole. The nature of their attachment to the heart wall can affect the understanding of their function. This attachment is conventionally portrayed as a direct connection of their bases to the solid portion of the heart wall. X-ray multidetector CT provides a new, noninvasive way to investigate this connection in vivo. METHODS AND RESULTS: With the use of x-ray multidetector CT with interactive 3D reconstruction, the bases of the PMs are seen to attach to the trabeculae carneae lining the ventricular wall rather than directly to the solid portion of the wall, as has been conventionally believed. This is true for both the left and right ventricular PMs. CONCLUSIONS: This new picture of the geometry of the attachment of the PMs to the heart wall may have important implications for the understanding of their function, including the nature of the transmission of the forces between the PMs and the heart wall

Clocks tick, bridges and skyscrapers vibrate, neuronal networks oscillate. Are neuronal oscillations an inevitable by-product, similar to bridge vibrations, or an essential part of the brain's design? Mammalian cortical neurons form behavior-dependent oscillating networks of various sizes, which span five orders of magnitude in frequency. These oscillations are phylogenetically preserved, suggesting that they are functionally relevant. Recent findings indicate that network oscillations bias input selection, temporally link neurons into assemblies, and facilitate synaptic plasticity, mechanisms that cooperatively support temporal representation and long-term consolidation of information

A major question in cell biology is how molecular specificity is achieved by different growth factor receptors that activate apparently identical signaling events. For the neurotrophin family, a distinguishing feature is the ability to maintain a prolonged duration of signal transduction. However, the mechanisms by which neurotrophin receptors assemble such a sustained signaling complex are not understood. Here we report that an unusual ankyrin-rich transmembrane protein (ARMS+kidins220) is closely associated with Trk receptor tyrosine kinases, and not the EGF receptor. This association requires interactions between transmembrane domains of Trk and ARMS. ARMS is rapidly tyrosine phosphorylated after binding of neurotrophins to Trk receptors and provides a docking site for the CrkL-C3G complex, resulting in Rap1-dependent sustained ERK activation. Accordingly, disruption of Trk-ARMS or the ARMS-CrkL interaction with dominant-negative ARMS mutants, or treatment with small interference RNA against ARMS substantially reduce neurotrophin-elicited signaling to ERK, but without any effect upon Ras or Akt activation. These findings suggest that ARMS acts as a major and neuronal-specific platform for prolonged MAP kinase signaling by neurotrophins

Increasing evidence points to synaptic plasticity impairment as one of the first events in Alzheimer's disease (AD). However, studies on synaptic dysfunction in different transgenic AD models that overexpress familial AD mutant forms of amyloid precursor protein (APP) and/or presenilin (PS) have provided conflicting results. Both long-term potentiation (LTP) and basal synaptic transmission (BST) have been found to be both unchanged and altered in different models and under differing experimental conditions. Because of their more robust amyloid-beta (Abeta) deposition, double transgenic mice currently are used by several laboratories as an AD model. Here, we report that mice overexpressing APP (K670N:M671L) together with PS1 (M146L) have abnormal LTP as early as 3 months of age. Interestingly, reduced LTP paralleled plaque appearance and increased Abeta levels and abnormal short-term memory (working memory). BST and long-term memory (reference memory) are impaired only later (approximately 6 months) as amyloid burden increases. Abeta pathology across different ages did not correlate with synaptic and cognitive deficits, suggesting that Abeta levels are not a marker of memory decline. In contrast, progression of LTP impairment correlated with the deterioration of working memory, suggesting that percentage of potentiation might be an indicator of the cognitive decline and disease progression in the APP/PS1 mice

Pericardial disease and its consequences can be well shown with magnetic resonance imaging (MRI) and computed tomography (CT). Here I review the normal and pathologic anatomy and physiology of the pericardium, approaches to MRI and CT imaging of the pericardium, and some specific considerations in common conditions affecting the pericardium