The yak genome and adaptation to life at high altitude

Domestic yaks (Bos grunniens) provide meat and other necessities for Tibetans living at high altitude on the Qinghai-Tibetan Plateau and in adjacent regions. Comparison between yak and the closely related low-altitude cattle (Bos taurus) is informative in studying animal adaptation to high altitude. Here, we present the draft genome sequence of a female domestic yak generated using Illumina-based technology at 65-fold coverage. Genomic comparisons between yak and cattle identify an expansion in yak of gene families related to sensory perception and energy metabolism, as well as an enrichment of protein domains involved in sensing the extracellular environment and hypoxic stress. Positively selected and rapidly evolving genes in the yak lineage are also found to be significantly enriched in functional categories and pathways related to hypoxia and nutrition metabolism. These findings may have important implications for understanding adaptation to high altitude in other animal species and for hypoxia-related diseases in humans.     

Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells

Chemokines have a central role in regulating processes essential to the immune function of T cells, such as their migration within lymphoid tissues and targeting of pathogens in sites of inflammation. Here we track T cells using multi-photon microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8+ T cells to control the pathogen Toxoplasma gondii in the brains of chronically infected mice. This chemokine boosts T-cell function in two different ways: it maintains the effector T-cell population in the brain and speeds up the average migration speed without changing the nature of the walk statistics. Notably, these statistics are not Brownian; rather, CD8+ T-cell motility in the brain is well described by a generalized Lévy walk. According to our model, this unexpected feature enables T cells to find rare targets with more than an order of magnitude more efficiency than Brownian random walkers. Thus, CD8+ T-cell behaviour is similar to Lévy strategies reported in organisms ranging from mussels to marine predators and monkeys, and CXCL10 aids T cells in shortening the average time taken to find rare targets.     

Initial sequencing and analysis of the human genome

The human genome holds an extraordinary trove of information about human development, physiology, medicine and evolution. Here we report the results of an international collaboration to produce and make freely available a draft sequence of the human genome. We also present an initial analysis of the data, describing some of the insights that can be gleaned from the sequence.     

Strong quantum-confined Stark effect in germanium quantum-well structures on silicon

Silicon is the dominant semiconductor for electronics, but there is now a growing need to integrate such components with optoelectronics for telecommunications and computer interconnections. Silicon-based optical modulators have recently been successfully demonstrated; but because the light modulation mechanisms in silicon are relatively weak, long (for example, several millimetres) devices or sophisticated high-quality-factor resonators have been necessary. Thin quantum-well structures made from III-V semiconductors such as GaAs, InP and their alloys exhibit the much stronger quantum-confined Stark effect (QCSE) mechanism, which allows modulator structures with only micrometres of optical path length. Such III-V materials are unfortunately difficult to integrate with silicon electronic devices. Germanium is routinely integrated with silicon in electronics, but previous silicon-germanium structures have also not shown strong modulation effects. Here we report the discovery of the QCSE, at room temperature, in thin germanium quantum-well structures grown on silicon. The QCSE here has strengths comparable to that in III-V materials. Its clarity and strength are particularly surprising because germanium is an indirect gap semiconductor; such semiconductors often display much weaker optical effects than direct gap materials (such as the III-V materials typically used for optoelectronics). This discovery is very promising for small, high-speed, low-power optical output devices fully compatible with silicon electronics manufacture.     

A physiological correlate of disuse-induced sprouting at the neuromuscular junction.

Recent investigations have established that many of the normal properties of muscle fibres are maintained, at least in part, by muscle activity. Thus, a fall in resting membrane potential, an increase in input resistance, and spread of acetylcholine receptors to extrajunctional sites can all be induced by abolishing muscle activity and prevented by direct stimulation of denervated muscle fibres. Muscle activity also exerts a trophic influence on the innervating motoneurones; furthermore it may be a factor in the regulation of sprouting. Brown and Ironton found fine, "ultra-terminal sprouts" emanating from the endplates of muscles rendered inactive by chronic conduction block of the muscle nerve. Pestronk and Drachman saw increased branching of the motor nerve terminal and a consequent increase in endplate size in similar conditions. If these sprouts at the endplates of inactive muscles were functional, one might expect more transmitter to be released in response to nerve stimulation. We report here that both quantum content and spontaneous miniature endplate potential (m.e.p.p) frequency are increased at the terminals of inactive (disused) muscles.     

Earthquake triggering by seismic waves following the Landers and Hector Mine earthquakes

The proximity and similarity of the 1992, magnitude 7.3 Landers and 1999, magnitude 7.1 Hector Mine earthquakes in California permit testing of earthquake triggering hypotheses not previously possible. The Hector Mine earthquake confirmed inferences that transient, oscillatory 'dynamic' deformations radiated as seismic waves can trigger seismicity rate increases, as proposed for the Landers earthquake. Here we quantify the spatial and temporal patterns of the seismicity rate changes. The seismicity rate increase was to the north for the Landers earthquake and primarily to the south for the Hector Mine earthquake. We suggest that rupture directivity results in elevated dynamic deformations north and south of the Landers and Hector Mine faults, respectively, as evident in the asymmetry of the recorded seismic velocity fields. Both dynamic and static stress changes seem important for triggering in the near field with dynamic stress changes dominating at greater distances. Peak seismic velocities recorded for each earthquake suggest the existence of, and place bounds on, dynamic triggering thresholds. These thresholds vary from a few tenths to a few MPa in most places, depend on local conditions, and exceed inferred static thresholds by more than an order of magnitude. At some sites, the onset of triggering was delayed until after the dynamic deformations subsided. Physical mechanisms consistent with all these observations may be similar to those that give rise to liquefaction or cyclic fatigue.     

A role for lateral hypothalamic orexin neurons in reward seeking

The lateral hypothalamus is a brain region historically implicated in reward and motivation, but the identity of the neurotransmitters involved are unknown. The orexins (or hypocretins) are neuropeptides recently identified as neurotransmitters in lateral hypothalamus neurons. Although knockout and transgenic overexpression studies have implicated orexin neurons in arousal and sleep, these cells also project to reward-associated brain regions, including the nucleus accumbens and ventral tegmental area. This indicates a possible role for these neurons in reward function and motivation, consistent with previous studies implicating these neurons in feeding. Here we show that activation of lateral hypothalamus orexin neurons is strongly linked to preferences for cues associated with drug and food reward. In addition, we show that chemical activation of lateral hypothalamus orexin neurons reinstates an extinguished drug-seeking behaviour. This reinstatement effect was completely blocked by prior administration of an orexin A antagonist. Moreover, administration of the orexin A peptide directly into the ventral tegmental area also reinstated drug-seeking. These data reveal a new role for lateral hypothalamus orexin neurons in reward-seeking, drug relapse and addiction.