In This Issue
GEOPHYSICS
Multiple rupture modes in experiments mimicking earthquakes
Large, destructive earthquakes are caused by dynamic ruptures along faults in the earth's crust. Seismic inversion and numerical modeling studies have revealed much about rupture scenarios. However, such studies have been limited by data availability, resolution, and a partial knowledge of fault friction and initial conditions. Xiao Lu et al. designed a geometrically simple setup that reproduced some of the basic physics governing rupture dynamics of crustal earthquakes. The authors simulated the earth's crust with a photoelastic plate, represented a fault using an inclined interface, applied far-field pressure that resulted in resolved shear and compressive load on the fault, and initiated dynamic ruptures with a local wire explosion. The researchers observed both pulse- and crack-like rupture modes, as well as a systematic transition between them during different initial stress conditions. In crack-like modes, all points behind the rupture front continued to slide for the duration of the experiment, whereas in pulse-like modes, the interface sealed, or “healed,” itself shortly after the passage of the rupture front. The authors discovered that either mode could transition to supershear speeds, enhancing the earthquake's destructive capability. — F.A.
Pulse rupture captured by high-speed camera and laser velocimeters.
“Pulse-like and crack-like ruptures in experiments mimicking crustal earthquakes” by Xiao Lu, Nadia Lapusta, and Ares J. Rosakis (see pages 18931–18936)
GENETICS
Mobile DNA leads to mutation
Genomic DNA is not a static repository of base pairs. Short pieces of DNA called transposons can pop out and reinsert themselves in different locations. Mutation, however, can result if a transposon interrupts a gene. Hiroki Kano et al. discovered that the mutation that leads to a specific limb deformity in mice is caused by one such transposon shift. Mice born with missing central digits have a condition, dactylaplasia, that depends on not one, but two genetic loci. The authors investigated how the interactions of these two loci led to missing digits. For a mouse to develop dactylaplasia, the Dac locus must be mutated, and the mouse must also have a recessive allele known as mdac. Mice with the dominant form, Mdac, do not develop dactylaplasia even if they have a mutated Dac allele. The authors found that the mutation originated from a provirus known to insert itself into genes, usually without any obvious effect. Their examination of DNA alteration patterns led the authors to conclude that Mdac silences the Dac insertion. — T.H.D.
Mouse displaying dactylaplasia.
“Genetically regulated epigenetic transcriptional activation of retrotransposon insertion confers mouse dactylaplasia phenotype” by Hiroki Kano, Hiroki Kurahashi, and Tatsushi Toda (see pages 19034–19039)
MEDICAL SCIENCES
Maternal history of Alzheimer's raises risk
A family history of Alzheimer's disease (AD) confers increased risk of late-onset AD, but the biological mechanisms for this risk are not known. Normal individuals with a parent affected with AD have a 4- to 10-fold higher risk of developing the disease compared to those with a negative family history. Previous research using positron emission tomography (PET) revealed that AD patients have reduced brain glucose metabolism in specific regions: parietotemporal, posterior cingulate, and medial temporal lobes, and to a lesser extent, frontal cortices. These reductions in glucose metabolism are one of the early hallmarks of the disease and occur many years before behaviorial symptoms manifest. Lisa Mosconi et al. used PET scans to compare brain glucose metabolism among 49 cognitively normal individuals who had a maternal history of AD, a paternal history of AD, or no family history of the disease. A reduced glucose metabolism in AD-vulnerable brain regions was found only in individuals who had a maternal family history of AD, which may predispose these individuals to develop AD in late life, according to the authors. — B.T.
Brain areas showing reduced glucose metabolism.
“Maternal family history of Alzheimer's disease predisposes to reduced brain glucose metabolism” by Lisa Mosconi, Miroslaw Brys, Remigiusz Switalski, Rachel Mistur, Lidia Glodzik, Elizabeth Pirraglia, Wai Tsui, Susan De Santi, and Mony J. de Leon (see pages 19067–19072)
MEDICAL SCIENCES
High-powered macrophages hasten diabetes
Type 2 diabetes is associated with defects in mitochondria, which link glucose production to insulin secretion. Yalin Emre et al. show that mitochondrial proteins are also connected to the development of type 1 diabetes through a different mechanism. Unlike type 2, type 1 diabetes develops as an autoimmune disease when the body destroys insulin-producing cells. The authors investigated the role of the mitochondrial protein UCP2 by inducing type 1 diabetes in wild-type mice and in those missing the gene for UCP2. UCP2 controls the activation of macrophages, roving sentinels of the immune system. Mice lacking UCP2 developed autoimmune diabetes in half the time observed for control mice. Emre et al. found that macrophages in mice missing UCP2 were better able to infiltrate the pancreas and secreted more chemical signals than in mice with the protein. This higher macrophage activity creates an inflammatory state and hastens the destruction of insulin-producing cells, leading to type 1 diabetes. In addition to showing a unique role for mitochondrial proteins in type 1 diabetes, this work opens new avenues for exploring the role of UCP2 in other autoimmune diseases, according to the authors. — T.H.D.
Early signs of increased macrophage infiltration, showing minor lymphocytic damage.
“Role of uncoupling protein UCP2 in cell-mediated immunity: How macrophage-mediated insulitis is accelerated in a model of autoimmune diabetes” by Yalin Emre, Corinne Hurtaud, Melis Karaca, Tobias Nubel, Flora Zavala, and Daniel Ricquier (see pages 19085–19090)
MICROBIOLOGY
Genes found for deadly mushroom toxins
In fungi, until now, all known cyclic peptides were thought to be produced by nonribosomal peptide synthases (NRPSs), with each enzyme dedicated to making only one peptide. Heather Hallen et al. shotgun-sequenced the genome of Amanita bisporigera (the “destroying angel”) and found that α-amanitin and phallotoxin, cyclic toxins responsible for fatal mushroom poisoning by Amanita mushrooms, are expressed from genes in the mushrooms' genomes. After a search turned up no matches to the DNA coding for known NRPSs, the authors searched for cyclic permutations of the amino acids coding for amanitins and phallotoxins. Indeed, the mushroom genome contained an amanitin gene, AMA1, and two copies of a phallacidin gene, PHA1. Amanitin is an octapeptide and phallacidin is a heptapeptide; the genetic material was padded out with three introns per gene, along with conserved flanking regions. A further search revealed an entire family of genes in A. bisporigera with similar flanking regions. In A. phalloides, the authors found AMA1, PHA1, and two related genes; AMA and PHA1 were not found in nonfatal Amanita species. These results, the authors say, explain why Amanitas outside section Phalloidae are not deadly. — K.M.
A. bisporigera, the “destroying angel.”
“Gene family encoding the major toxins of lethal Amanita mushrooms” by Heather E. Hallen, Hong Luo, John S. Scott-Craig, and Jonathan D. Walton (see pages 19097–19101)
