Semiconductor Lasers: Two in One
Unipolar devices have an advantage over bipolar ones in that they can be operated independent of the polarity of the applied voltage—they are bidirectional. Gmachl et al. (p. 749) have now designed quantum cascade lasers that can be operated bidirectionally. Moreover, through careful design of the series of quantum wells that make up the injection region of the laser, they show that a tailored asymmetry can produce lasing at two different wavelengths, depending on the polarity.
Amyloid Secret(ase) Revealed
Alzheimer's disease is characterized by the progressive formation in the brain of insoluble deposits containing the amyloid β peptide (Aβ). This peptide is generated when the amyloid precursor protein (APP) is cleaved by two distinct and long-sought proteases, the β- and γ-secretases. Vassar et al. (p. 735; see the news story by Pennisi) have identified a transmembrane aspartic protease, beta-site APP cleaving enzyme, or BACE, that has all of the known characteristics of the β-secretase. Future development of BACE-specific inhibitors will allow testing in animal models of Aβ's role in Alzheimer's disease and may lead to new treatments for the disease.
Inorganic Electronics from Solution
The majority of inorganic electronic devices used today are fabricated in a series of steps that require deposition of inorganic species from the gas phase. These processes are performed at relatively high temperatures and are often rather expensive. Ridley et al. (p. 746) introduce an alternative, and potentially cheaper, all-solution route that takes advantage of the reduced melting point of nanocrystals. Cadmium selenide (CdSe) nanoparticles, formed by mixing cadmium iodide and sodium selinide, were suspended in pyridine. The resulting solution was then printed onto a substrate, and a subsequent low-temperature annealing process drives off the pyridine to leave behind a thin film of CdSe. The authors demonstrate the potential of such a process by fabricating thin film transistors with good electrical characteristics
Repeated abrupt climate changes occurred during the long buildup of ice sheets toward the Last Glacial Maximum (LGM). Detailed oceanic records of these events and their effects on sea surface temperatures (SSTs) are scarce, yet important for understanding the mechanisms and extent of abrupt climate change. Sachs and Lehman (p. 756) now provide a high-resolution marine record from the Bermuda Rise of SSTs spanning the period from 30,000 to 60,000 years ago. The record shows several cases where SSTs increased abruptly by 2° to 5°C, which is comparable to the change observed from the LGM to the Holocene. These events parallel those seen in Greenland records. The periods of warming appeared to have been unstable and were followed by either abrupt or continued gradual cooling. Thus, the abrupt climate changes seen in the ice core records affected tropical oceans.
Slowing Getting More Complex
The issue of complexity in evolution has generated interest in biology, but it has been notoriously difficult to measure the dynamics of complexity in the fossil record. Saunders et al. (p. 760) describe the evolution of complexity in the septal sutures of an extinct group of mollusks—ammonoids—in more than 500 genera during the 140 million years from the Devonian to the Triassic, a period that includes three mass extinctions. Although mass extinctions tended to eliminate more complex structures, the large-scale evolutionary trend was toward increased complexity. Thus, they show that two non-random evolutionary trends acted in opposition—a within-lineage-driven bias for increased suture complexity and an among-lineage differential extinction of more complex forms during times of biotic crisis.
The Middle to Late Triassic (about 225 to 230 million years ago) was a crucial period in the early evolution of dinosaurs, yet little has been known about the faunal composition at that time. Flynn et al. (p. 763) now report the discovery of a fossil fauna in Madagascar that contains newly identified dinosaur and eucynodont (mammal-like reptiles) taxa. Their discovery represents a major new source of terrestrial vertebrate fossils for a time period that is sampled poorly elsewhere in the world; the dinosaurs may be more ancient than any others worldwide; and the recovery of the eucynodont fills in a 170-million-year gap in the fossil record of the region.
Stability with Maturity
Signaling through the transmembrane protein Notch occurs in a variety of tissues in order to determine cell fates during development. Sestan et al. (p. 741; see the Perspective by Chenn and Walsh) show that Notch signaling is also important in the already differentiated neurons of the mature cerebral cortex. The various protein components of the signaling pathway are found in dendrites and control dendrite extension.
Further clues into the regulation of circadian clocks are the subject of two reports. In plants and insects, cryptochromes (CRYs) are activated by light, and in the fruit fly Drosophila, CRY blocks the negative feedback action of the PER-TIM complex. Griffin et al. (p. 768) show that CRY1 and CRY2 play a central role in the mammal clock, but in a light-independent fashion—they appear to regulate transcriptional cycling of Per1 by contacting both the activator and its feedback inhibitors. In Drosophila, three of the critical clock genes, period (per), timeless (tim), and Drosophila Clock (dClk), are expressed rhythmically. In their study of the cycling of dClk, Glossop et al. (p. 766) have found that the molecular clock in Drosophila is composed of two interlocked negative feedback loops—the per-tim loop, which is activated by the dCLK and CYCLE proteins and repressed by PER-TIM, and the dClk loop, in which these proteins exert the opposite effect.
Interfering with TGF-Beta
Unregulated cell growth results in tumor production; therefore, it is important to identify developmental factors that regulate cell growth. Transforming growth factor-β (TGF-β) regulates cell growth and differentiation through receptor-mediated phosphorylation of Smad proteins. These Smad proteins in turn form protein complexes and enter the cell's nucleus to activate the transcription of target genes. Stroschein et al. (p. 771; see the news story by Vogel) have identified a new player, SnoN, in TGF-β signaling. In the absence of TGF-β, the SnoN oncoprotein binds to a Smad2/Smad4 complex and recruits a transcription co-repressor, thus inhibiting transcription activation. When TGF-β is present, Smad3 triggers the degradation of SnoN and transcription activation resumes. Finally, a negative-feedback mechanism is present in which TGF-β stimulates SnoN production, which then represses the transcription activation function of the Smad complex once again. SnoN is found in various carcinomas. Hence, the transforming activity of SnoN may be explained by its interference with the role of TGF-β in inhibiting cell growth.
To Live or Let Die
The release of intracellular calcium (Ca2+) can trigger signals that lead to cell survival or to cell death; two reports illustrate how the same transcription factor, MEF2, which functions in the differentiation of skeletal muscle, can play different roles in the survival of neurons and T cells. During development of the mammalian brain, neurons that make proper synaptic connections and receive signals from other cells experience an increase in the intracellular Ca2+. This Ca2+ influx promotes cell survival or resistance to cell death. Mao et al. (p. 785) present evidence that MEF2 mediates the pro-survival effects of Ca2+ in cultured neuronal cells from the rat cerebral cortex. The increase in Ca2+ apparently causes activation of the p38 mitogen-activated protein kinase, which may directly phosphorylate and activate MEF2. Neuronal survival thus appears to be modulated through transcriptional regulation by MEF2, as well as through posttranslational changes in components of the cell death machinery. Activation of mature T cells eventually leads to their demise. It is thought that expression of the Nur77 orphan steroid receptor, whose transcription is dependent on Ca2+, the phosphatase calcineurin, and the transcription factor MEF2, mediates this apoptosis. Youn et al. (p. 790) have begun to elucidate the regulation of Nur77 expression and T cell apoptosis. Endogenous MEF2 is bound by Cabin 1, an inhibitor of calcineurin. When intracellular Ca2+ increases, calmodulin competes for binding to Cabin 1 at the same site as MEF2 and forces the release of MEF2, which makes it available for assembly into the transcriptional complex.
Some Disassembly Required
The dynamics of the mitotic spindle is regulated in part by katanin, an enzyme that localizes to centrosomes. However, just how this AAA-type adenosine triphosphatase severs microtubles of the spindle has been unclear. Hartman and Vale (p. 782) now reveal the mechanism by which katanin forms a stable multimeric ring. Katanin oligomerization is driven by binding to its substrate, microtubules, and by binding to the nucleotide ATP. Hence, microtubules that comprise the mitotic spindle may assist their own disassembly by serving as a scaffold onto which katanin assembles.
Accumulating Damage with Age
One hypothesis for the cause of aging is that mutations accumulate in mitochondrial DNA (mtDNA). However, previous searches, which have generally studied protein- or RNA-coding regions of mtDNA, have yielded numerous types of age-related mutations, but these occur only at low frequencies (a few percent). Michikawa et al. (p. 774; see the news story by Pennisi) have studied the main control region for replication of mtDNA and found frequent point mutations in normal older subjects that were not found in normal young subjects. In particular, a TG transversion was found in up to 50% of the mtDNA molecules from 8 of 14 older subjects that did not appear in mtDNA of 13 younger subjects. Longitudinal studies of three individuals help show that these mutations are not inherited.
Structural Probe into Iron Metabolism
The transferrin receptor (TfR) delivers transferrin-associated iron into cells for use in a variety of physiological processes, including cell growth. The receptor also binds HFE, the protein that is defective in human hereditary hemochromatosis, an iron storage disease that affects 1 in 300 individuals of northern European origin. Lawrence et al. (p. 779) determined the three-dimensional crystal structure of the extracellular domain of TfR. The structure revealed a monomer of three domains, one of which resembles carboxy- and aminopeptidases. This work provides a structural foundation for future studies of how iron uptake and release are controlled in the cell
Mid-Ocean Ridge Resistance
Mid-ocean ridges are linear structures where sea-floor spreading occurs by the passive upwelling of melt to form new oceanic crust that then cools and is pulled away from the ridge by subduction at the other end of the spreading plates. The dynamics of the melt upwelling is poorly understood because it is difficult to determine the structure of the magma reservoirs at mid-ocean ridges. Evans et al. (p. 752) have measured the electrical resistivity of the East Pacific rise at 17°S. They found low resistivities to the west of the ridge, which would be consistent with a low melt fraction over a broad area that is distributed asymmetrically on one side of the ridge. The asymmetry of the melt distribution is consistent with asymmetric spreading and a westward migration of the ridge in this area. [See the Perspective by Buck.]