Hafting, which allowed projectile points to be attached to a staff, was an important technological advance that greatly increased the functionality of weapons of early humans. This technology was used by both Neandertals and early Homo sapiens and is readily seen after about 200,000 to 300,000 years ago, but whether it was used by a common ancestor or was separately acquired by each species is unclear. Supporting use by a common ancestor, Wilkins et al. (p. 942) report that stone points in a site in central South Africa were hafted to form spears around 500,000 years ago. The evidence includes damaged edges consistent with this use and marks at the base that are suggestive of hafting.
Nanotube Yarn Actuators
Actuators are used to convert heat, light, or electricity into a twisting or tensile motion, and are often described as artificial muscles. Most materials that show actuation either provide larger forces with small-amplitude motions, such as the alloy NiTi, or provide larger motions with much less force, such as polymeric materials. Other problems with such actuators can include slow response times and short lifetimes. Lima et al. (p. 928, see the Perspective by Schulz) show that a range of guest-filled, twist-spun carbon nanotube yarns can be used for linear or torsional actuation, can solve the problems of speed and lifetime, and do not require electrolytes for operation.
Channels from DNA
Artificial transmembrane channels are of interest for applications, such as sensing and modifying cell signaling. Langecker et al. (p. 932; see the Perspective by Strano) used α-hemolysin as a model for creating a nanostructure with DNA origami that, when inserted into a lipid bilayer membrane, acted as a membrane channel. Ion channel responses were similar to those measured for natural ion channels, and channels that protruded further into the membrane exhibited greater gating responses. The channels were used to detect single-DNA molecules.
Coherent Heat Flow
Typically, heat in solids is transported incoherently because phonons scatter at interfaces and defects. Luckyanova et al. (p. 936) grew super-lattice films made from one to nine repeats of layers of GaAs and AlAs, each 12-nm thick. Thermal conductivity through this sandwich structure increased linearly with the number of superlattice repeats, which is consistent with theoretical simulations of coherent heat transport.
The origin of pallasite meteorites seems to defy explanation because their main constituents—iron and olivine—should have segregated into layers inside their parent body. The generally accepted model suggests that they formed at the core-mantle boundary of an asteroid. Tarduno et al. (p. 939; see the Perspective by Weiss) measured a remnant magnetization in olivine crystals of two pallasite meteorites and conclude that a dynamo must have operated in their parent body, providing further evidence that some asteroids were capable of dynamo generation. The data, together with thermal modeling, suggest that some pallasites could have formed when liquid FeNi from the core of an impacting asteroid was injected into the mantle of a large protoplanet.
Experience Versus Models
There is an ongoing debate over what the orbitofrontal cortex contributes to behavior, learning, and decision-making. Jones et al. (p. 953) found that the orbitofrontal cortex was important for value-based computations when value must be inferred from an associative model of the task but not when value estimates based on previous experience are sufficient. This result calls into question the assumption that this region simply signals economic value. However, it would be consistent with a concept of the orbitofrontal cortex as being important for constructing model-based representations of the world that are orthogonal to value.
Getting Autophagy to Akt
The protein kinase Akt is often activated in human cancers and is thought to promote tumor formation. One way in which it may do so is to inhibit autophagy (a process by which the cell digests its own proteins or organelles, especially damaged ones). Wang et al. (p. 956, published online 25 October; see the Perspective by Koren and Kimchi) provide a direct molecular mechanism by which Akt regulates autophagy. Beclin, a component of the autophagy machinery, appears to be a direct target of phosphorylation by Akt. Such phosphorylation enhanced interaction of Beclin with intermediate filaments of the cyto skeleton and inhibited autophagy. Expression of a modified Beclin 1 molecule that could not be phosphorylated by Akt inhibited Akt-induced transformation of cells in culture and tumor formation in a mouse model.
Removing Typhoid Restriction
Some bacterial pathogens exhibit exquisite host adaptation and can only infect a single host. For example, Salmonella enterica serovar Typhi (S. Typhi), the cause of typhoid fever, can only infect humans. The host restriction is manifested at the cellular level because S. Typhi is unable to survive within macrophages of species other than human. Spanò and Galán (p. 960) found that expression of a single type-III secretion effector protein from a broad host Salmonella in S. Typhi, allowed this human-exclusive pathogen to survive within macrophages from a nonpermissive host. Furthermore, S. Typhi expressing this effector was able to replicate within mice, a nonpermissive host.
How to Hear
In mammalian ears, a chain of biophysical events allows for the translation of airborne acoustic energy into mechanical vibrations that can be detected by mechanosensory cells in the cochlear. Mammalian ears have been considered largely unique in this transformation because it is the delicate, mammalian-specific, bones of the middle ear that facilitate this transmission, known as impedence conversion. In most other vertebrates the bones that make up the middle ear function as part of the lower jaw, limiting the potential for vertebrate convergence in this process. However, Montealegre-Z. et al. (p. 968, see the Perspective by Hoy) show that the rainforest katydid, an insect with ears on its hind legs, have converged on a similar three step impedence conversion process using a unique tympanum-lever organ. This convergence, across millions of years of evolutionary distance, shows the flexibility of morphology to adapt to biophysical challenges.
Parkinson's disease (PD) and related α-synucleinopathies are defined by the accumulation of α-synuclein (α-Syn)–containing intraneuronal inclusions—Lewy bodies (LBs) and Lewy neurites (LNs)—in association with the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and other brain regions. However, a cause-and-effect relationship between LB/LN formation and neurodegeneration remains unclear. Indeed, whether LB/LNs are toxic or represent a neuroprotective response has been contentious. Luk et al. (p. 949) injected α-Syn fibrils generated from recombinant mouse α-Syn protein into the dorsal striatum of wild-type mice and found that misfolded α-Syn caused the formation of PD-like LB/LNs and subsequent cell-to-cell transmission of pathologic α-Syn to anatomically interconnected regions, including the SNpc. Furthermore, the formation of LB/LNs and their accumulation in SNpc resulted in the progressive loss of these dopaminergic neurons, reduced dopamine innervations to the dorsal striatum, and culminated in motor deficits similar to PD. Thus, a synthetic misfolded wild-type protein (that is, α-Syn) was able to elicit and transmit disease pathology and neurodegeneration in healthy nontransgenic mice.
Artificially Induced Oocytes
In mice, male embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs) have been shown to differentiate into primordial germ cell–like cells (PGCLCs) in vitro. Upon transplantation into testes, these PGCLCs can form fully functional sperm. Again working in mice, Hayashi et al. (p. 971, published online 4 October) found that female ESCs and iPSCs can also differentiate into PGCLCs, which, when aggregated in reconstituted ovaries, exhibited epigenetic reprogramming and meiotic potential in vitro. Upon transplantation of the reconstituted ovaries under ovarian bursa, female PGCLCs developed into fully grown oocytes that contributed to healthy offspring upon in vitro maturation and fertilization.
Helping T Helper Transcription
Members of the interferon response family of transcription factors (IRFs) are specifically expressed in immune cells and are known to regulate their differentiation. IRF4 and IRF8 regulate gene expression by binding to other transcription factors, which results in their recruitment to composite motifs in the genome. Although the specific mechanism of how this regulation works in some immune cells is understood, how it occurs in T cells is not clear because the transcription factors that normally partner with IRFs are absent. Using genomic analysis, Glasmacher et al. (p. 975, published online 13 September; see the Perspective by Martinez and Rao) now identify IRF4–AP-1 composite elements in T helper 17 (TH17) cells and show that IRF4 and the AP-1 factor Batf cooperatively assemble on a large array of genes required for TH17 cell differentiation and function. Assembly of such heterodimers was also observed in TH2 cells, B cells, and dendritic cells, which suggests the general importance of this motif in immune cell differentiation.
Costs of Conservation
In 2010, world governments agreed to a strategic plan for biodiversity conservation, including 20 targets to be met by 2020, through the Convention on Biological Diversity. Discussions on financing the plan have still not been resolved, partly because there is little information on the likely costs of meeting the targets. McCarthy et al. (p. 946, published online 11 October) estimate the financial costs for two of the targets relating to protected areas and preventing extinctions. Using data from birds, they develop models that can be extrapolated to the costs for biodiversity more broadly. Reducing extinction risk for all species is estimated to require in the region of U.S. $4 billion annually, while the projected costs of establishing and maintaining protected areas may be as much as U.S. $58 billion—although both sums are small, relative to the economic costs of ecosystem losses.
Salmonella is one of the most intensively studied bacterial pathogens. The Salmonella-containing vacuole (SCV) has a paradoxical lysosome-like composition: On one hand, the SCV membrane is highly enriched in lysosomal membrane glycoproteins and SCVs are accessible to endolysosomal content, but on the other hand, SCV lumen is relatively devoid of lysosomal hydrolytic enzymes that are delivered by the mannose-6-phosphate receptor pathway. McGourty et al. (p. 963) resolve this paradox by showing that the Salmonella effector SifA interferes with the trafficking of mannose-6-phosphate receptors. This causes misrouting and secretion of lysosomal enzymes and reduces the hydrolytic activity of lysosomes. Intracellular growth of Salmonella was reduced in cells with enhanced lysosomal enzyme activity.