Although there are many proposals for implementing molecular electronics, three-terminal devices such as transistors are one of the most promising architectures. Molecular transistors have been recently demonstrated using many thousands of molecules in a single monolayer, Schön et al. (p. 2138) now demonstrate switching confined to single molecules, which addresses the challenges of reducing energy dissipation and enabling large-scale integration.
Solar Output and Climate Change
Changes in solar output, although relatively small, can apparently exert large effects on climate (see the Perspective by Haigh). Periodic episodes of surface-water cooling accompanied by increases in iceberg formation and transport have recurred in the North Atlantic throughout the last 100,000 years. Bond et al. (p. 2130; see the 16 November news story by Kerr) now show that virtually all of the centennial-scale expansions of cooler surface waters in the North Atlantic during the past 12,000 years were tied to decreases in the production of the cosmogenic nuclides 14C and 10Be. This finding strongly links these events to changes in solar irradiance and indicate that mechanisms to amplify small variations in solar forcing must exist. Between the mid-1600s and the early 1700s, when global average surface temperatures were generally among the lowest of the last millennium, there was a minimum in solar irradiance called the Maunder Minimum. Shindell et al. (p. 2149) use a general circulation model to evaluate possible mechanisms for temperature differences between the Maunder Minimum and those of a century later, when solar output remained relatively high for several decades. Their reconstructions suggest that solar-forced climate change during the Maunder Minimum was a result of a reduction in the intensity of the Arctic Oscillation/North Atlantic Oscillation, and that regional cooling over the continents during winter was as much as five times greater than the decrease of global average temperatures.
Carbon Dioxide Cycles on Mars
As Mars turns in its orbit around the Sun, seasonal changes at different latitudes are driven by the exchange of CO2 between the atmosphere and the ice caps (see the Perspective by Paige). Smith et al. (p. 2141) used changes in elevation measured by the Mars Orbiter Laser Altimeter and Doppler tracking, both from the Mars Global Surveyor (MGS) spacecraft, to track the variation in CO2 snow depth at different latitudes as each polar cap sublimates CO2 in its summer season for transport to the opposite hemisphere, where it recondenses as snow. Malin et al. (p. 2146; see the cover) used images of the south polar cap, collected over a martian year by the Mars Orbiter Camera onboard MGS to measure the retreat of escarpments in the ice. The inferred rate of CO2 sublimation was greater than expected and suggests that Mars may be in the midst of a major global climate change in which the polar caps are losing mass to the atmosphere.
The depth of the lysocline, where the transition between preservation and dissolution of sedimentary calcium carbonate occurs, differs between the major ocean basins. Its location depends partly on carbonate ion concentration and thus is a sensitive indicator of ocean circulation. Broecker and Clark (p. 2152; see the Perspective by Archer and Martin) report measurements of shell weights of selected populations of foraminifera which show that during the Last Glacial Maximum, the Pacific lysocline was deeper and the Atlantic lysocline was shallower than today, and that both oceans exhibited large carbonate concentration gradients as a function of depth, unlike at the present. The greater contrast between the carbonate ion concentration in deep waters produced in the northern Atlantic and those in the Pacific compared to the present, reflects major differences in thermohaline circulation.
No New Neocortical Neurons
Indications that cells in the adult primate's brain might proliferate to form new neurons have stood in stark contrast with previous studies which found that neurons of the central nervous system leave their mitotic phase during development. Kornack and Rakic (p. 2127) used the indicator bromodeoxyuridine to identify proliferating cells in the brains of adult macaque monkeys. Dividing cells found in the neocortex were identified as nonneuronal supporting cells; proliferation of neurons was limited to the hippocampus and olfactory bulb. Thus, whereas certain types of new cells may indeed be found in the adult brain, the contribution of these cells to complex neuronal functions may be only secondary.
A Model of Portliness
Individuals with visceral (intra-abdominal) obesity are particularly prone to develop a cluster of metabolic disturbances, termed “metabolic syndrome,” that include glucose intolerance, insulin resistance, plasma lipid disorders, and hypertension. Because visceral obesity has been associated with high levels of glucocorticoids, Masuzaki et al. (p. 2166; see the news story by Gura) studied the role of 11β hydroxysteroid dehydrogenase type 1 (11β HSD-1), an enzyme that can amplify glucocorticoid action and is overexpressed in the adipose tissue of obese humans. Transgenic mice that modestly overexpressed 11β HSD-1 in adipose tissue developed visceral obesity and, remarkably, displayed many of the defining features of the metabolic syndrome.
Taking on Drug Resistance
The Staphylococcus aureus protein QacR represses transcription of the qacA multidrug transporter gene. QacR also binds diverse cationic lipophilic drugs, and drug binding induces expression of the qacA gene. Schumacher et al. (p. 2158) have determined the structures of six QacR-drug complexes. Drug binding causes a conformational change, relative to DNA-bound QacR, that causes induction and creates an extended multidrug-binding pocket. The bacterium Streptococcus pneumoniae, the major cause of the ear infection acute otitis media and more seriously of meningitis, pneumonia, and lethal sepsis, is present in an asymptomatic carrier state in the respiratory tracts of many children. This reservoir can pass drug-resistant strains to susceptible individuals. Loeffler et al. (p. 2170) have built upon technology developed against S. aureus in which a lytic enzyme was used to kill bacteria in the respiratory tract. In a mouse model of nasal infection, 1400 units of the enzyme Pal, an amidase from phage Dp-1, applied into the nose and mouth eliminated the bacteria. This treatment should not affect other bacteria, and resistant bacteria did not appear after extensive enzyme exposure.
The epithelium of the mouse small intestine contains secretory three cell types (the goblet cells, enteroendocrine cells, and Paneth cells) and absorptive enterocytes. Yang et al. (p. 2155; see the Perspective by van den Brink et al.) examined whether the factor Math1, which is found in the intestine and reported to be necessary for cell fate determination in the central nervous system, is involved in gut cell determination. In mice that lack functional Math1, the secretory cells failed to differentiate and the progenitors remained in the proliferating stage. However, the loss of Math1 did not affect the enterocytes.
Getting Used to a Smell
In vertebrate olfactory neurons, odor molecules stimulate the opening of cyclic nucleotide-gated channels (CNGs). The resulting influx of Ca2+ions also triggers a negative-feedback mechanism in which channel activity is inhibited when bound to a Ca2+-calmodulin (CaM) complex. This mechanism promotes olfactory adaptation and allows animals to continually evaluate the odor environment. Two groups have determined that two of the channel's three subunits are required for odor adaptation. Munger et al. (p. 2172) show that channels from mice lacking the CNGA4 subunit exhibited slower Ca2+-CaM-mediated inhibition. Bradley et al. (p. 2176) have used a heterologous expression system to show that both the CNGA4 and CNGB1b subunits facilitate Ca2+-CaM binding to the open state of channel.
Cut and Run to the Nucleus
The conventional view of receptor tyrosine kinase-mediated signal transduction holds that upon ligand binding, a signaling cascade initiated at the cell surface ultimately regulates gene expression. Although it has been proposed that such receptors may localize to the nucleus to affect transcription directly, the mechanism for nuclear translocation has not been clear. Ni et al. (p. 2179; see the Perspective by Heldin and Ericsson) show that cleavage of ErbB-4, an epidermal growth factor receptor family member, by presenilin-dependent-secretase releases a transcriptionally active intracellular domain of ErbB-4 to the nucleus. In the absence of this cleavage, the ErbB-4 ligand could not modulate cell growth.
Bigger Is Not Better
The tumor suppressor gene Pten also plays a critical role for normal brain development. Standard Pten deletion mutants in mice are lethal in early development, so Groszer et al. (p. 2186; see the Perspective by Penniger and Woodgett) developed a conditional knockout that deletes PTEN in the central nervous system at mid-gestation. These mice showed hyperactivation of certain signal transduction pathways; they also exhibited enlarged brains with multiple malformations, and more and bigger neural cells. Analysis of cell proliferation and apoptosis in the mutant brains suggests that PTEN controls progression of neural progenitor cells through the cell cycle.
Anomalous Vortex Dynamics in Cuprate Superconductors
One of the more straightforward applications of superconductors is to use them as resistance-free interconnects. However, when superconductors are placed in a magnetic field, small magnetic flux lines (or vortices), penetrate the superconductor, and unless they are “pinned” (that is, immobile), they dissipate energy and eventually destroy the superconductivity. At low temperature, these vortices are frozen and form a regular triangular lattice, but as the temperature is raised closer to the transition temperature to the normal state, they become mobile. Understanding vortex dynamics is therefore thought to be crucial in developing practical applications. Matsuda et al. (p. 2136) used a newly developed high-resolution Lorentz microscope to reveal anomalous behavior in the high-temperature superconducting cuprates in which the regular triangular lattice is observed, but with alternately spaced lines of vortices. They report that the lines of vortices become mobile before those in the triangular lattice, which may suggest a limitation to their application.
Chromosomes in Motion
Chromosome movement not only occurs during cell division, but also takes place during the rest of the cell cycle. Heun et al. (p. 2181) found that yeast chromosomes undergo large, rapid, energy-dependent movements during the G1 phase (the growth or “resting” phase) of the cell cycle. These movements become constraining during the subsequent S (synthesis) phase of the cell cycle, a constriction that is dependent on DNA replication, which suggests that replication foci impede chromosomal movements. The authors suggest that the anchoring of centromeres and telomeres to the periphery of the nuclear envelope during these periods may help define the overall position of the chromosomes in the nucleus.
Selectively Seeing Sugars
Cells use surface receptors to sense their surroundings. Although many of the best-characterized receptors detect the presence of small molecules, such as adrenaline, equally important functions are subserved by receptors that interact transiently (or loosely) with environmental macromolecules, either located on other cells or within the extracellular matrix. Feinberg et al. (p. 2163) present the crystal structures of two such receptors, DC-SIGN [dendritic cell specific intracellular adhesion molecule-3 (ICAM-3) grabbing nonintegrin] and a related receptor, DC-SIGNR, that recognize carbohydrate moieties of macromolecules. DC-SIGN grabs onto ICAM-3, a surface molecule expressed by T cells, and this interaction forms part of the process of dendritic cell activation of T cells. DC-SIGNR is an endothelial cell component that may mediate the initial stages by which circulating cells scan the surfaces of capillaries and lymph nodes. Both of these receptors are coerced by the human immunodeficiency virus into binding to the HIV protein gp120 before the virus enters T cells.
Crustaceans and the "Cambrian Explosion"
Siveter et al. (Reports, 20 July 2001, p. 479) described fossils of a phosphatocopid arthropod from Lower Cambrian strata in Shropshire, England, that provide “evidence for the occurrence of Crustacea, including Eucrustacea, in the Early Cambrian” and support “the hypothesis … of a late Precambrian history for the Metazoa.” Fortey (Perspectives, 20 July 2001, p. 438) noted that the work raises doubts about the suddenness and rapidity of the Cambrian evolutionary “explosion.” Budd et al., in a comment, raise questions about some of the phylogenetic relationships proposed by Siveter et al., and point out that the fossils “postdate the base of the Cambrian by some 32 million years … well beyond the range appropriate for testing Cambrian Explosion hypotheses.” Siveter et al. offer a defense of their taxonomy. They also note that their fossil is “at most a few million years younger” than the age during which the “Cambrian evolutionary radiation achieved its ‘explosive’ character”—and that their analysis, coupled with evidence from other fossil assemblages, suggests a much earlier origin for the arthropod evolutionary line. The full text of these comments can be seen at www.sciencemag.org/cgi/content/full/294/5549/2047a