My Summer Reading

Published: September 1st, 2016

Category: The Flight

imagesRecommendations from my readings include:

  • The Wright Brothers by David McCullough
  • The Violinist’s Thumb by Sam Kean

In addition to the above you should read the following:

What happens in utero does not stay in utero

The concept that what happens to us in utero will influence our health later in life has been supported by several recent epidemiological and clinical observations. For example, prenatal exposure to a farm environment modifies a newborn’s atopic sensitization. We know that both environmental and genetic factors contribute to the programming of our immune system, and the very first environment we are exposed to is within our mother’s uterus. Thus, in utero immune programming may be a key event in establishing our early immune system and have significant long-term impact on early human health. A recent Early Human Development publication puts us a step closer to understanding the mechanism of in utero immune system reprogramming. The paper’s senior author James Wynn of the Department of Pediatrics and his team define how preterm exposure to histologic chorioamnionitis (HCA), an inflammation of the placental chorionic disk and the extraplacental membranes, can dramatically reprogram the transcriptome of cells within the fetal immune system. It will now be interesting to dissect both the positive and negative consequences of this in utero immune reprogramming on the ability of children to fight postnatal infections.

Weitkamp, J., Guthrie, S., Wong, H., Moldawer, L., Baker, H., & Wynn, J. (2016). Histological chorioamnionitis shapes the neonatal transcriptomic immune response.

Laura made a mouse:

Laura and her team made a mouse. So, what’s the big deal? To put this accomplishment into context, you need to step back and review the challenge of the translating detailed molecular genetics to impactful therapies to improve the human condition. Laura Ranum and Maury Swanson study the fascinating group of genetic disorders caused by nucleotide repeat expansions. Their team has explored the detailed mechanisms whereby nucleotide expansions may perturb cellular function. They propose two, perhaps not mutually exclusive, mechanisms. The first involves a negative consequence of production of large amounts of RNA from these repeat stretches that may interfere with cellular functions; the second involves the exciting observation that these repeats may actually produce translatable RNAs from all reading frames, which in turn produces a series of protein aggregates that the cell cannot handle. How we nail down the link between these proposed mechanisms and disease progression, and how we target these pathological entities to develop effective treatments will both depend on animal models that accurately reproduce the human disease. As reported in Neuron, Laura and her team have succeeded where others have failed by producing a BAC mouse model of C9orff72 that demonstrates ALS/FTD phenotype and exhibits both upregulated antisense RNA and RAN protein accumulation. The availability of this mouse will now be integral to the development of new ALS/FTD therapies.

Liu, Y., Pattamatta, A., Zu, T., Reid, T., Bardhi, O., Borchelt, D., Yachnis, A., & Ranum, L. (2016). C9orf72 BAC mouse model with motor deficits and neurodegenerative features of ALS/FTD.

Neuro tract-tracing goes real time:

When I was in graduate school, I took separate courses in neuroanatomy and neurophysiology. Even in these early (very early) days, it was readily apparent that the lack of structure-function integration was holding back the field of neurobiology. Well times certainly have changed! Habibeh Khoshbouei’s group (Department of Neuroscience) contributed a paper to Nature Communications highlighting the power of state-of-the-art neurobiology. Using real-time confocal and total internal reflection fluorescence (TIRF) microscopy coupled to electrophysiology and optogenetics, they define the dynamic redistribution of dopamine transporter (DAT) in response changes membrane potential, which in turn may impact extracellular dopamine levels. These observations will have fundamental bearing on the way we view the interplay between synaptic activity, synaptic composition and contents of the synaptic space.

Richardson, B., Saha, K., Krout, D., Cabrera, E., Felts, B., Henry, L., Swant, J., Zou, M., Newman, A., & Khoshbouei, H. (2016). Membrane potential shapes regulation of dopamine transporter trafficking at the plasma membrane.