The DNA sequence and comparative analysis of human chromosome 5

Chromosome 5 is one of the largest human chromosomes and contains numerous intrachromosomal duplications, yet it has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding conservation with non-mammalian vertebrates, suggesting that they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-coding genes including the protocadherin and interleukin gene families. We also completely sequenced versions of the large chromosome-5-specific internal duplications. These duplications are very recent evolutionary events and probably have a mechanistic role in human physiological variation, as deletions in these regions are the cause of debilitating disorders including spinal muscular atrophy.     

SHRIMP U-Pb geochronology of the zircons from the Precambrian basement of the Qilian Block and its geological significances

Origin and tectonic evolution of the Qilian Precambrian basement on NW China were investigated using zircon U-Pb ages with collaborating stratigraphic and paleontological evidence. Zircon grains were separated from two schists, two granitic gneisses and one mylonized gneiss and dated with SHRIMP. Seventy percent of sixty-one detrital zircon ages from two schists ranges from 0.88 Ga to 3.09 Ga, mostly within 1.0 Ga to 1.8 Ga with a peak at 1.6 Ga to 1.8 Ga, and twenty percent varies from 2.0 Ga to 2.5 Ga. A few falls in the Archean and Neoproterozoic periods. The two granitic gneisses were dated 930±8 Ma and 918±14 Ma, whereas the mylonized granitic gneiss was dated 790±12 Ma. These ages represent two periods of magmatisms, which can be correlated with the early and late stages of magmatisms associated with the Jinningian movement on the Yangtze Blocks. The results from this and previous studies indicate that the ages of the Precambrian detrital zircons from the Qilian Block are widely distributed in the Proterozoic era, distinct from the North China Block which was stable in the Neo-Mesoproterozoic era. By contrast, the age histograms of the detrital zircons from the Qilian Block is similar to those from Precambrian basement of the Yangtze Craton. Therefore, it is suggested that the Qilian Block had a strong affinity toward the Yangtze Craton and might belong to the supercontinent Gondwana in the Neoproterozoic time. This inference is supported by Nd model age (TDM), stratigraphic, and paleontological evidence. It is further considered that the Qilian Block was rifted from the supercontinent Gondwana during late Sinian to form an isolated continent in the Proto-Tethyan Ocean, moving towards the Alaxa Block in the North China Craton. The part of Proto-Tethyan Ocean between the Qilian and Alaxa Blocks should correspond to the so-called Paleo-Qilian Ocean. Following the closure of the Paleo-Qilian Ocean in the early Paleozoic, the Qilian Block collided with the Alaxa Block to form the North Qilian Orogenic Belt. Based on this tectonic explanation, the North Qilian ophiolites should represent parts of lithosphere from the Proto-Tethyan Ocean. Lithological and geochronological evidence also indicates that the Qilian Block underwent continental reactivation possibly induced by the deep northward subduction of the North Qaidam Block in early Paleozoic time.     

Epigenetic maintenance of the vernalized state in Arabidopsis thaliana requires LIKE HETEROCHROMATIN PROTEIN 1

Vernalization is the process by which sensing a prolonged exposure to winter cold leads to competence to flower in the spring. In winter annual Arabidopsis thaliana accessions, flowering is suppressed in the fall by expression of the potent floral repressor FLOWERING LOCUS C (FLC). Vernalization promotes flowering via epigenetic repression of FLC. Repression is accompanied by a series of histone modifications of FLC chromatin that include dimethylation of histone H3 at Lys9 (H3K9) and Lys27 (H3K27). Here, we report that A. thaliana LIKE HETEROCHROMATIN PROTEIN 1 (LHP1) is necessary to maintain the epigenetically repressed state of FLC upon return to warm conditions typical of spring. LHP1 is enriched at FLC chromatin after prolonged exposure to cold, and LHP1 activity is needed to maintain the increased levels of H3K9 dimethylation at FLC chromatin that are characteristic of the vernalized state.     

Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes

Gastric cancer is a major cause of global cancer mortality. We surveyed the spectrum of somatic alterations in gastric cancer by sequencing the exomes of 15 gastric adenocarcinomas and their matched normal DNAs. Frequently mutated genes in the adenocarcinomas included TP53 (11/15 tumors), PIK3CA (3/15) and ARID1A (3/15). Cell adhesion was the most enriched biological pathway among the frequently mutated genes. A prevalence screening confirmed mutations in FAT4, a cadherin family gene, in 5% of gastric cancers (6/110) and FAT4 genomic deletions in 4% (3/83) of gastric tumors. Frequent mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) also occurred in 47% of the gastric cancers. We detected ARID1A mutations in 8% of tumors (9/110), which were associated with concurrent PIK3CA mutations and microsatellite instability. In functional assays, we observed both FAT4 and ARID1A to exert tumor-suppressor activity. Somatic inactivation of FAT4 and ARID1A may thus be key tumorigenic events in a subset of gastric cancers.     

Optogenetic stimulation of a hippocampal engram activates fear memory recall

A specific memory is thought to be encoded by a sparse population of neurons. These neurons can be tagged during learning for subsequent identification and manipulation. Moreover, their ablation or inactivation results in reduced memory expression, suggesting their necessity in mnemonic processes. However, the question of sufficiency remains: it is unclear whether it is possible to elicit the behavioural output of a specific memory by directly activating a population of neurons that was active during learning. Here we show in mice that optogenetic reactivation of hippocampal neurons activated during fear conditioning is sufficient to induce freezing behaviour. We labelled a population of hippocampal dentate gyrus neurons activated during fear learning with channelrhodopsin-2 (ChR2) and later optically reactivated these neurons in a different context. The mice showed increased freezing only upon light stimulation, indicating light-induced fear memory recall. This freezing was not detected in non-fear-conditioned mice expressing ChR2 in a similar proportion of cells, nor in fear-conditioned mice with cells labelled by enhanced yellow fluorescent protein instead of ChR2. Finally, activation of cells labelled in a context not associated with fear did not evoke freezing in mice that were previously fear conditioned in a different context, suggesting that light-induced fear memory recall is context specific. Together, our findings indicate that activating a sparse but specific ensemble of hippocampal neurons that contribute to a memory engram is sufficient for the recall of that memory. Moreover, our experimental approach offers a general method of mapping cellular populations bearing memory engrams.     

Crystal structure of a membrane-embedded H+-translocating pyrophosphatase

H(+)-translocating pyrophosphatases (H(+)-PPases) are active proton transporters that establish a proton gradient across the endomembrane by means of pyrophosphate (PP(i)) hydrolysis. H(+)-PPases are found primarily as homodimers in the vacuolar membrane of plants and the plasma membrane of several protozoa and prokaryotes. The three-dimensional structure and detailed mechanisms underlying the enzymatic and proton translocation reactions of H(+)-PPases are unclear. Here we report the crystal structure of a Vigna radiata H(+)-PPase (VrH(+)-PPase) in complex with a non-hydrolysable substrate analogue, imidodiphosphate (IDP), at 2.35?? resolution. Each VrH(+)-PPase subunit consists of an integral membrane domain formed by 16 transmembrane helices. IDP is bound in the cytosolic region of each subunit and trapped by numerous charged residues and five Mg(2+) ions. A previously undescribed proton translocation pathway is formed by six core transmembrane helices. Proton pumping can be initialized by PP(i) hydrolysis, and H(+) is then transported into the vacuolar lumen through a pathway consisting of Arg?242, Asp?294, Lys?742 and Glu?301. We propose a working model of the mechanism for the coupling between proton pumping and PP(i) hydrolysis by H(+)-PPases.     

A stability limit for the atmospheres of giant extrasolar planets

Recent observations of the planet HD209458b indicate that it is surrounded by an expanded atmosphere of atomic hydrogen that is escaping hydrodynamically. Theoretically, it has been shown that such escape is possible at least inside an orbit of 0.1 au (refs 4 and 5), and also that H3+ ions play a crucial role in cooling the upper atmosphere. Jupiter's atmosphere is stable, so somewhere between 5 and 0.1 au there must be a crossover between stability and instability. Here we show that there is a sharp breakdown in atmospheric stability between 0.14 and 0.16 au for a Jupiter-like planet orbiting a solar-type star. These results are in contrast to earlier modelling that implied much higher thermospheric temperatures and more significant evaporation farther from the star. (We use a three-dimensional, time-dependent coupled thermosphere-ionosphere model and properly include cooling by H3+ ions, allowing us to model globally the redistribution of heat and changes in molecular composition.) Between 0.2 and 0.16 au cooling by H3+ ions balances heating by the star, but inside 0.16 au molecular hydrogen dissociates thermally, suppressing the formation of H3+ and effectively shutting down that mode of cooling.