Simulating the amplification of orbital forcing by ocean feedbacks in the last glaciation

According to Milankovitch theory, the lower summer insolation at high latitudes about 115,000 years ago allowed winter snow to persist throughout summer, leading to ice-sheet build-up and glaciation. But attempts to simulate the last glaciation using global atmospheric models have failed to produce this outcome when forced by insolation changes only. These results point towards the importance of feedback effects-for example, through changes in vegetation or the ocean circulation-for the amplification of solar forcing. Here we present a fully coupled ocean-atmosphere model of the last glaciation that produces a build-up of perennial snow cover at known locations of ice sheets during this period. We show that ocean feedbacks lead to a cooling of the high northern latitudes, along with an increase in atmospheric moisture transport from the Equator to the poles. These changes agree with available geological data and, together, they lead to an increased delivery of snow to high northern latitudes. The mechanism we present explains the onset of glaciation-which would be amplified by changes in vegetation-in response to weak orbital forcing.     

Unconscious priming eliminates automatic binding of colour and alphanumeric form in synaesthesia

Synaesthesia is an unusual perceptual phenomenon in which events in one sensory modality induce vivid sensations in another. Individuals may 'taste' shapes, 'hear' colours, or 'feel' sounds. Synaesthesia was first described over a century ago, but little is known about its underlying causes or its effects on cognition. Most reports have been anecdotal or have focused on isolated unusual cases. Here we report an investigation of 15 individuals with colour-graphemic synaesthesia, each of whom experiences idiosyncratic but highly consistent colours for letters and digits. Using a colour-form interference paradigm, we show that induced synaesthetic experiences cannot be consciously suppressed even when detrimental to task performance. In contrast, if letters and digits are presented briefly and masked, so that they are processed but unavailable for overt report, the synaesthesia is eliminated. These results show that synaesthetic experiences can be prevented despite substantial processing of the sensory stimuli that otherwise trigger them. We conclude that automatic binding of colour and alphanumeric form in synaesthesia arises after initial processes of letter and digit recognition are complete.     

Covalent inhibition revealed by the crystal structure of the caspase-8/p35 complex

Apoptosis is a highly regulated process that is crucial for normal development and homeostasis of multicellular organisms. The p35 protein from baculoviruses effectively prevents apoptosis by its broad-spectrum caspase inhibition. Here we report the crystal structure of p35 in complex with human caspase-8 at 3.0 A resolution, and biochemical and mutagenesis studies based on the structural information. The structure reveals that the caspase is inhibited in the active site through a covalent thioester linkage to p35, which we confirmed by gel electrophoresis, hydroxylamine treatment and mass spectrometry experiments. The p35 protein undergoes dramatic conformational changes on cleavage by the caspase. The repositioning of the amino terminus of p35 into the active site of the caspase eliminates solvent accessibility of the catalytic dyad. This may be crucial for preventing hydrolysis of the thioester intermediate, which is supported by the abrogation of inhibitory activity through mutations at the N terminus of p35. The p35 protein also makes conserved contacts with the caspase outside the active-site region, providing the molecular basis for the broad-spectrum inhibitory activity of this protein. We demonstrate a new molecular mechanism of caspase inhibition, as well as protease inhibition in general.     

Guard cell abscisic acid signalling and engineering drought hardiness in plants

Guard cells are located in the epidermis of plant leaves, and in pairs surround stomatal pores. These control both the influx of CO2 as a raw material for photosynthesis and water loss from plants through transpiration to the atmosphere. Guard cells have become a highly developed system for dissecting early signal transduction mechanisms in plants. In response to drought, plants synthesize the hormone abscisic acid, which triggers closing of stomata, thus reducing water loss. Recently, central regulators of guard cell abscisic acid signalling have been discovered. The molecular understanding of the guard cell signal transduction network opens possibilities for engineering stomatal responses to control CO2 intake and plant water loss.     

Interhemispheric climate links revealed by late-glacial cooling episode in southern Chile

Understanding the relative timings of climate events in the Northern and Southern hemispheres is a prerequisite for determining the causes of abrupt climate changes. But climate records from the Patagonian Andes and New Zealand for the period of transition from glacial to interglacial conditions--about 14.6-10 kyr before present, as determined by radiocarbon dating--show varying degrees of correlation with similar records from the Northern Hemisphere. It is necessary to resolve these apparent discrepancies in order to be able to assess the relative roles of Northern Hemisphere ice sheets and oceanic, atmospheric and astronomical influences in initiating climate change in the late-glacial period. Here we report pollen records from three sites in the Lake District of southern Chile (41 degrees S) from which we infer conditions similar to modern climate between about 13 and 12.2 14C kyr before present (BP), followed by cooling events at about 12.2 and 11.4 14C kyr BP, and then by a warming at about 9.8 14C kyr BP. These events were nearly synchronous with important palaeoclimate changes recorded in the North Atlantic region, supporting the idea that interhemispheric linkage through the atmosphere was the primary control on climate during the last deglaciation. In other regions of the Southern Hemisphere, where climate events are not in phase with those in the Northern Hemisphere, local oceanic influences may have counteracted the effects that propagated through the atmosphere.     

Guide to the draft human genome

There are a number of ways to investigate the structure, function and evolution of the human genome. These include examining the morphology of normal and abnormal chromosomes, constructing maps of genomic landmarks, following the genetic transmission of phenotypes and DNA sequence variations, and characterizing thousands of individual genes. To this list we can now add the elucidation of the genomic DNA sequence, albeit at 'working draft' accuracy. The current challenge is to weave together these disparate types of data to produce the information infrastructure needed to support the next generation of biomedical research. Here we provide an overview of the different sources of information about the human genome and how modern information technology, in particular the internet, allows us to link them together.     

Involvement of chemokine receptors in breast cancer metastasis

Breast cancer is characterized by a distinct metastatic pattern involving the regional lymph nodes, bone marrow, lung and liver. Tumour cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. Here we report that the chemokine receptors CXCR4 and CCR7 are highly expressed in human breast cancer cells, malignant breast tumours and metastases. Their respective ligands CXCL12/SDF-1alpha and CCL21/6Ckine exhibit peak levels of expression in organs representing the first destinations of breast cancer metastasis. In breast cancer cells, signalling through CXCR4 or CCR7 mediates actin polymerization and pseudopodia formation, and subsequently induces chemotactic and invasive responses. In vivo, neutralizing the interactions of CXCL12/CXCR4 significantly impairs metastasis of breast cancer cells to regional lymph nodes and lung. Malignant melanoma, which has a similar metastatic pattern as breast cancer but also a high incidence of skin metastases, shows high expression levels of CCR10 in addition to CXCR4 and CCR7. Our findings indicate that chemokines and their receptors have a critical role in determining the metastatic destination of tumour cells.     

New hominin genus from eastern Africa shows diverse middle Pliocene lineages

Most interpretations of early hominin phylogeny recognize a single early to middle Pliocene ancestral lineage, best represented by Australopithecus afarensis, which gave rise to a radiation of taxa in the late Pliocene. Here we report on new fossils discovered west of Lake Turkana, Kenya, which differ markedly from those of contemporary A. afarensis, indicating that hominin taxonomic diversity extended back, well into the middle Pliocene. A 3.5 Myr-old cranium, showing a unique combination of derived facial and primitive neurocranial features, is assigned to a new genus of hominin. These findings point to an early diet-driven adaptive radiation, provide new insight on the association of hominin craniodental features, and have implications for our understanding of Plio-Pleistocene hominin phylogeny.