Diurnal modulation of pacemaker potentials and calcium current in the mammalian circadian clock

The central biological clock of the mammalian brain is located in the suprachiasmatic nucleus. This hypothalamic region contains neurons that generate a circadian rhythm on a single-cell basis. Clock cells transmit their circadian timing signals to other brain areas by diurnal modulation of their spontaneous firing rate. The intracellular mechanism underlying rhythm generation is thought to consist of one or more self-regulating molecular loops, but it is unknown how these loops interact with the plasma membrane to modulate the ionic conductances that regulate firing behaviour. Here we demonstrate a diurnal modulation of Ca2+ current in suprachiasmatic neurons. This current strongly contributes to the generation of spontaneous oscillations in membrane potential, which occur selectively during daytime and are tightly coupled to spike generation. Thus, day-night modulation of Ca2+ current is a central step in transducing the intracellular cycling of molecular clocks to the rhythm in spontaneous firing rate.     

Detection of carbonates in dust shells around evolved stars.

Carbonates on large Solar System bodies like Earth and Mars (the latter represented by the meteorite ALH84001) form through the weathering of silicates in a watery (CO3)2- solution. The presence of carbonates in interplanetary dust particles and asteroids (again, represented by meteorites) is not completely understood, but has been attributed to aqueous alteration on a large parent body, which was subsequently shattered into smaller pieces. Despite efforts, the presence of carbonates outside the Solar System has hitherto not been established. Here we report the discovery of the carbonates calcite and dolomite in the dust shells of evolved stars, where the conditions are too primitive for the formation of large parent bodies with liquid water. These carbonates, therefore, are not formed by aqueous alteration, but perhaps through processes on the surfaces of dust or ice grains or gas phase condensation. The presence of carbonates which did not form by aqueous alteration suggests that some of the carbonates found in Solar System bodies no longer provide direct evidence that liquid water was present on large parent bodies early in the history of the Solar System.     

Recombinational DNA double-strand breaks in mice precede synapsis

In Saccharomyces cerevisiae, meiotic recombination is initiated by Spo11-dependent double-strand breaks (DSBs), a process that precedes homologous synapsis. Here we use an antibody specific for a phosphorylated histone (gamma-H2AX, which marks the sites of DSBs) to investigate the timing, distribution and Spo11-dependence of meiotic DSBs in the mouse. We show that, as in yeast, recombination in the mouse is initiated by Spo11-dependent DSBs that form during leptotene. Loss of gamma-H2AX staining (which in irradiated somatic cells is temporally linked with DSB repair) is temporally and spatially correlated with synapsis, even when this synapsis is 'non-homologous'.     

SPTLC1 is mutated in hereditary sensory neuropathy, type 1

Hereditary sensory neuropathy type 1 (HSN1, MIM 162400; ref. 1) genetically maps to human chromosome 9q22 (refs. 2-4). We report here that the gene encoding a subunit of serine palmitoyltransferase is located within the HSN1 locus, expressed in dorsal root ganglia (DRG) and mutated in HSN1.     

Neanderthal cranial ontogeny and its implications for late hominid diversity

Homo neanderthalensis has a unique combination of craniofacial features that are distinct from fossil and extant 'anatomically modern' Homo sapiens (modern humans). Morphological evidence, direct isotopic dates and fossil mitochondrial DNA from three Neanderthals indicate that the Neanderthals were a separate evolutionary lineage for at least 500,000 yr. However, it is unknown when and how Neanderthal craniofacial autapomorphies (unique, derived characters) emerged during ontogeny. Here we use computerized fossil reconstruction and geometric morphometrics to show that characteristic differences in cranial and mandibular shape between Neanderthals and modern humans arose very early during development, possibly prenatally, and were maintained throughout postnatal ontogeny. Postnatal differences in cranial ontogeny between the two taxa are characterized primarily by heterochronic modifications of a common spatial pattern of development. Evidence for early ontogenetic divergence together with evolutionary stasis of taxon-specific patterns of ontogeny is consistent with separation of Neanderthals and modern humans at the species level.     

Dinosaurian growth rates and bird origins

Dinosaurs, like other tetrapods, grew more quickly just after hatching than later in life. However, they did not grow like most other non-avian reptiles, which grow slowly and gradually through life. Rather, microscopic analyses of the long-bone tissues show that dinosaurs grew to their adult size relatively quickly, much as large birds and mammals do today. The first birds reduced their adult body size by shortening the phase of rapid growth common to their larger theropod dinosaur relatives. These changes in timing were primarily related not to physiological differences but to differences in growth strategy.     

The bacterial conjugation protein TrwB resembles ring helicases and F1-ATPase

The transfer of DNA across membranes and between cells is a central biological process; however, its molecular mechanism remains unknown. In prokaryotes, trans-membrane passage by bacterial conjugation, is the main route for horizontal gene transfer. It is the means for rapid acquisition of new genetic information, including antibiotic resistance by pathogens. Trans-kingdom gene transfer from bacteria to plants or fungi and even bacterial sporulation are special cases of conjugation. An integral membrane DNA-binding protein, called TrwB in the Escherichia coli R388 conjugative system, is essential for the conjugation process. This large multimeric protein is responsible for recruiting the relaxosome DNA-protein complex, and participates in the transfer of a single DNA strand during cell mating. Here we report the three-dimensional structure of a soluble variant of TrwB. The molecule consists of two domains: a nucleotide-binding domain of alpha/beta topology, reminiscent of RecA and DNA ring helicases, and an all-alpha domain. Six equivalent protein monomers associate to form an almost spherical quaternary structure that is strikingly similar to F1-ATPase. A central channel, 20 A in width, traverses the hexamer.     

Four-terminal resistance of a ballistic quantum wire

The electrical resistance of a conductor is intimately related to the relaxation of the momentum of charge carriers. In a simple model, the accelerating force exerted on electrons by an applied electric field is balanced by a frictional force arising from their frequent collisions with obstacles such as impurities, grain boundaries or other deviations from a perfect crystalline order. Thus, in the absence of any scattering, the electrical resistance should vanish altogether. Here, we observe such vanishing four-terminal resistance in a single-mode ballistic quantum wire. This result contrasts the value of the standard two-probe resistance measurements of h/2e2 approximately 13 kOmega. The measurements are conducted in the highly controlled geometry afforded by epitaxial growth onto the cleaved edge of a high-quality GaAs/AlGaAs heterostructure. Two weakly invasive voltage probes are attached to the central section of a ballistic quantum wire to measure the inherent resistance of this clean one-dimensional conductor.     

The physical maps for sequencing human chromosomes 1, 6, 9, 10, 13, 20 and X

We constructed maps for eight chromosomes (1, 6, 9, 10, 13, 20, X and (previously) 22), representing one-third of the genome, by building landmark maps, isolating bacterial clones and assembling contigs. By this approach, we could establish the long-range organization of the maps early in the project, and all contig extension, gap closure and problem-solving was simplified by containment within local regions. The maps currently represent more than 94% of the euchromatic (gene-containing) regions of these chromosomes in 176 contigs, and contain 96% of the chromosome-specific markers in the human gene map. By measuring the remaining gaps, we can assess chromosome length and coverage in sequenced clones.