Axle-less F1-ATPase rotates in the correct direction

F1-adenosine triphosphatase (ATPase) is an ATP-driven rotary molecular motor in which the central gamma subunit rotates inside a cylinder made of three alpha and three beta subunits alternately arranged. The rotor shaft, an antiparallel alpha-helical coiled coil of the amino and carboxyl termini of the gamma subunit, deeply penetrates the central cavity of the stator cylinder. We truncated the shaft step by step until the remaining rotor head would be outside the cavity and simply sat on the concave entrance of the stator orifice. All truncation mutants rotated in the correct direction, implying torque generation, although the average rotary speeds were low and short mutants exhibited moments of irregular motion. Neither a fixed pivot nor a rigid axle was needed for rotation of F1-ATPase.     

Molecular cloning of the Bombyx mori prothoracicotropic hormone

Prothoracicotropic hormone (PTTH), a brain secretory polypeptide of insects, stimulates the prothoracic glands to produce and release ecdysone, the steroid essential to insect development. The complementary DNAs encoding PTTH of the silkmoth Bombyx mori were cloned and characterized, and the complete amino acid sequence was deduced. The data indicated that PTTH is first synthesized as a 224-amino acid polypeptide precursor containing three proteolytic cleavage signals. The carboxyl-terminal component (109 amino acids) that follows the last cleavage signal represents one PTTH subunit. Two PTTH subunits are linked together by disulfide bonds, before or after cleavage from prepro-PTTH, to form a homodimeric PTTH. When introduced into Escherichia coli cells, the complementary DNA directed the expression of an active substance that was functionally indistinguishable from natural PTTH. In situ hybridization showed the localization of the prepro-PTTH mRNA to two dorsolateral neurosecretory cells of the Bombyx brain.     

Differentiation of immature mucous cells into parietal, argyrophil, and chief cells in stomach grafts

Microscopic and submicroscopic studies on regenerating gastric mucosa neonatally grafted in the subcutaneous tissue of littermate mice have revealed that immature mucous cells are totipotent; ultimately they transform into mature mucous, parietal, argyrophil, and chief cells in the gastric glands.     

Success and virulence in Toxoplasma as the result of sexual recombination between two distinct ancestries

Toxoplasma gondii is a common human pathogen causing serious, even fatal, disease in the developing fetus and in immunocompromised patients. Despite its ability to reproduce sexually and its broad geographic and host range, Toxoplasma has a clonal population structure comprised principally of three lines. We have analyzed 15 polymorphic loci in the archetypal type I, II, and III strains and found that polymorphism was limited to, at most, two rather than three allelic classes and no polymorphism was detected between alleles in strains of a given type. Multilocus analysis of 10 nonarchetypal isolates likewise clustered the vast majority of alleles into the same two distinct ancestries. These data strongly suggest that the currently predominant genotypes exist as a pandemic outbreak from a genetic mixing of two discrete ancestral lines. To determine if such mixing could lead to the extreme virulence observed for some strains, we examined the F(1) progeny of a cross between a type II and III strain, both of which are relatively avirulent in mice. Among the progeny were recombinants that were at least 3 logs more virulent than either parent. Thus, sexual recombination, by combining polymorphisms in two distinct and competing clonal lines, can be a powerful force driving the natural evolution of virulence in this highly successful pathogen.     

A small molecule Smac mimic potentiates TRAIL- and TNFalpha-mediated cell death

We describe the synthesis and properties of a small molecule mimic of Smac, a pro-apoptotic protein that functions by relieving inhibitor-of-apoptosis protein (IAP)-mediated suppression of caspase activity. The compound binds to X chromosome- encoded IAP (XIAP), cellular IAP 1 (cIAP-1), and cellular IAP 2 (cIAP-2) and synergizes with both tumor necrosis factor alpha (TNFalpha) and TNF-related apoptosis-inducing ligand (TRAIL) to potently induce caspase activation and apoptosis in human cancer cells. The molecule has allowed a temporal, unbiased evaluation of the roles that IAP proteins play during signaling from TRAIL and TNF receptors. The compound is also a lead structure for the development of IAP antagonists potentially useful as therapy for cancer and inflammatory diseases.     

Orangutan cultures and the evolution of material culture

Geographic variation in some aspects of chimpanzee behavior has been interpreted as evidence for culture. Here we document similar geographic variation in orangutan behaviors. Moreover, as expected under a cultural interpretation, we find a correlation between geographic distance and cultural difference, a correlation between the abundance of opportunities for social learning and the size of the local cultural repertoire, and no effect of habitat on the content of culture. Hence, great-ape cultures exist, and may have done so for at least 14 million years.     

Protostellar feedback halts the growth of the first stars in the universe

The first stars fundamentally transformed the early universe by emitting the first light and by producing the first heavy elements. These effects were predetermined by the mass distribution of the first stars, which is thought to have been fixed by a complex interplay of gas accretion and protostellar radiation. We performed radiation-hydrodynamics simulations that followed the growth of a primordial protostar through to the early stages as a star with thermonuclear burning. The circumstellar accretion disk was evaporated by ultraviolet radiation from the star when its mass was 43 times that of the Sun. Such massive primordial stars, in contrast to the often-postulated extremely massive stars, may help explain the fact that there are no signatures of the pair-instability supernovae in abundance patterns of metal-poor stars in our galaxy.     

Integrating what and when across the primate medial temporal lobe

Episodic memory or memory for the detailed events in our lives is critically dependent on structures of the medial temporal lobe (MTL). A fundamental component of episodic memory is memory for the temporal order of items within an episode. To understand the contribution of individual MTL structures to temporal-order memory, we recorded single-unit activity and local field potential from three MTL areas (hippocampus and entorhinal and perirhinal cortex) and visual area TE as monkeys performed a temporal-order memory task. Hippocampus provided incremental timing signals from one item presentation to the next, whereas perirhinal cortex signaled the conjunction of items and their relative temporal order. Thus, perirhinal cortex appeared to integrate timing information from hippocampus with item information from visual sensory area TE.     

A planar rhombic charge-separated tetrasilacyclobutadiene

The cyclobutadiene (CBD) molecule C(4)H(4) deviates from a high-symmetry square geometry to compensate for its antiaromatic electronic structure. Here, we report a CBD silicon analog, Si(4)(EMind)(4) (1), stabilized by the bulky 1,1,7,7-tetraethyl-3,3,5,5-tetramethyl-s-hydrindacen-4-yl (EMind) groups, obtained as air- and moisture-sensitive orange crystals by the reduction of (EMind)SiBr(3) with three equivalents of lithium naphthalenide. X-ray crystallography reveals a planar and rhombic structure of the Si(4) four-membered ring, with alternating pyramidal and planar configurations at the silicon atoms. The large (29)Si chemical shift differences (Δδ > 350 parts per million) in the solid-state nuclear magnetic resonance spectra suggest a contribution of an alternately charge-separated structure. The rhombic-shaped charge-separated singlet state of compound 1 thus stabilizes its cyclic 4π-electron antiaromaticity in a manner that contrasts sharply with the bond-length alternation, characterizing the rectangular distortion of carbon-based CBD.