Christian Siriano at New York Fashion Week Fall 2014
Human neural progenitor cells isolated under selective culture conditions from the developing human brain and directed through lineage differentiation. Neural progenitor cells are stained green; differentiated astrocytes are orange. Nuclei are stained blue. Image courtesy of the National Institute of Neurological Disorders and Stroke.
Researchers at the University of California, San Diego School of Medicine have discovered that a well-known protein has a new function: It acts in a biological circuit to determine whether an immature neural cell remains in a stem-like state or proceeds to become a functional neuron.
The findings, published in the February 13 online issue of Cell Reports, more fully illuminate a fundamental but still poorly understood cellular act – and may have significant implications for future development of new therapies for specific neurological disorders, including autism and schizophrenia.
Postdoctoral fellow Chih-Hong Lou, working with principal investigator Miles F. Wilkinson, PhD, professor in the Department of Reproductive Medicine and a member of the UC San Diego Institute for Genomic Medicine, and other colleagues, discovered that this critical biological decision is controlled by UPF1, a protein essential for the nonsense-mediated RNA decay (NMD) pathway.
NMD was previously established to have two broad roles. First, it is a quality control mechanism used by cells to eliminate faulty messenger RNA (mRNA) – molecules that help transcribe genetic information into the construction of proteins essential to life. Second, it degrades a specific group of normal mRNAs. The latter function of NMD has been hypothesized to be physiologically important, but until now it had not been clear whether this is the case.
Wilkinson and colleagues discovered that in concert with a special class of RNAs called microRNA, UPF1 acts as a molecular switch to determine when immature (non-functional) neural cells differentiate into non-dividing (functional) neurons. Specifically, UPF1 triggers the decay of a particular mRNA that encodes for a protein in the TGF-? signaling pathway that promotes neural differentiation. By degrading that mRNA, the encoded protein fails to be produced and neural differentiation is prevented. Thus, Lou and colleagues identified for the first time a molecular circuit in which NMD acts to drive a normal biological response.
NMD also promotes the decay of mRNAs encoding proliferation inhibitors, which Wilkinson said may explain why NMD stimulates the proliferative state characteristic of stem cells.
“There are many potential clinical ramifications for these findings,” Wilkinson said. “One is that by promoting the stem-like state, NMD may be useful for reprogramming differentiated cells into stem cells more efficiently.
“Another implication follows from the finding that NMD is vital to the normal development of the brain in diverse species, including humans. Humans with deficiencies in NMD have intellectual disability and often also have schizophrenia and autism. Therapies to enhance NMD in affected individuals could be useful in restoring the correct balance of stem cells and differentiated neurons and thereby help restore normal brain function.”
Sunset in Finland at latitude 60 degrees north. The shallow angle of the setting and rising sun is typical at this high northern latitude. The photographer made multi exposures on a fixed film camera to create this photograph. - Pekka Parviainen.
Winged Figure Seated upon a Rock,Abbott Handerson Thayer (August 12, 1849 - May 29, 1921)
Vlada Roslyakova at Ralph Lauren f/w 2014
Max Bruch - Kol Nidrei, Op. 47
Jacqueline Du Pré, cello
Gerald Moore, piano
Before the first birds could take flight, they needed a lift from an unexpected source: colourful feathers. As well as giving birds the most colourful plumage on earth, it seems pigment factories in their feathers primed their feathery dinosaur ancestors for flight by creating feathers of many different shapes. The same pigment factories may also have turbocharged the proto-birds’ metabolism, helping them into the air.
This insight comes from a study of cellular pigment factories called melanosomes from the feathers, hairs and skin of 181 living birds, mammals and reptiles, plus 13 fossils of ancient lizards, turtles, dinosaurs and pterosaurs.
Julia Clarke of the University of Texas at Austin and her colleagues found that melanosomes suddenly became much more diverse in the lineage leading to birds. This happened at the same time that feather-like appendages appeared in maniraptoran dinosaurs, the forerunners of birds. These “pinnate” feathers resembled the familiar branched structure of modern bird feathers, and contained vastly more diverse melanosomes, in terms of their length, width and shape than the samples from ancient lizards and dinosaurs….
But it’s not just about feathers. The melanosome diversity explosion may also have led to higher metabolic rates in the forerunners of birds. Such rapid metabolisms are essential for powered flight.
"Many of the genes involved in the melanin colour system are also involved in other core processes such as food intake, stress responses, reproductive behaviour and more," says Clarke. That means the change in pigment could be linked to larger changes in the animals’ energetics and physiology.
This is corroborated by the modern animals, where melanosome diversity is linked to metabolism. “Only in living warm-blooded terrestrial vertebrates which independently evolved higher metabolic rates did we find the melanosome diversity we also see in feathered dinosaurs,” says Clarke.
(via New Scientist)
Photo: Analysis for the distribution of shapes of melanin-containing organelles (melanosomes) in fossil and living amniotes shows that fuzz-covered dinosaurs like Sinosauropteryx share similarities with living lizards, turtles and crocodilians. In these living taxa color and the shape of the melanosomes are not linked in such a way that color can be reconstructed from melanosome shape alone. Melanosomes in Sinosauropteryx don’t presently tell us if this animal was brown, blackish or grey. However, feathered dinosaurs are similar to birds, and we can estimate their color. Credit: Li et al. (authors).
Journal reference: Nature, DOI: 10.1038/nature12973
Rooney Mara as Alex DeLarge
OH DEAR LORD