Spatio-temporal correlations and visual signalling in a complete neuronal population

Statistical dependencies in the responses of sensory neurons govern both the amount of stimulus information conveyed and the means by which downstream neurons can extract it. Although a variety of measurements indicate the existence of such dependencies, their origin and importance for neural coding are poorly understood. Here we analyse the functional significance of correlated firing in a complete population of macaque parasol retinal ganglion cells using a model of multi-neuron spike responses. The model, with parameters fit directly to physiological data, simultaneously captures both the stimulus dependence and detailed spatio-temporal correlations in population responses, and provides two insights into the structure of the neural code. First, neural encoding at the population level is less noisy than one would expect from the variability of individual neurons: spike times are more precise, and can be predicted more accurately when the spiking of neighbouring neurons is taken into account. Second, correlations provide additional sensory information: optimal, model-based decoding that exploits the response correlation structure extracts 20% more information about the visual scene than decoding under the assumption of independence, and preserves 40% more visual information than optimal linear decoding. This model-based approach reveals the role of correlated activity in the retinal coding of visual stimuli, and provides a general framework for understanding the importance of correlated activity in populations of neurons.     

Structure of a tyrosyl-tRNA synthetase splicing factor bound to a group I intron RNA

The 'RNA world' hypothesis holds that during evolution the structural and enzymatic functions initially served by RNA were assumed by proteins, leading to the latter's domination of biological catalysis. This progression can still be seen in modern biology, where ribozymes, such as the ribosome and RNase P, have evolved into protein-dependent RNA catalysts ('RNPzymes'). Similarly, group I introns use RNA-catalysed splicing reactions, but many function as RNPzymes bound to proteins that stabilize their catalytically active RNA structure. One such protein, the Neurospora crassa mitochondrial tyrosyl-tRNA synthetase (TyrRS; CYT-18), is bifunctional and both aminoacylates mitochondrial tRNA(Tyr) and promotes the splicing of mitochondrial group I introns. Here we determine a 4.5-A co-crystal structure of the Twort orf142-I2 group I intron ribozyme bound to splicing-active, carboxy-terminally truncated CYT-18. The structure shows that the group I intron binds across the two subunits of the homodimeric protein with a newly evolved RNA-binding surface distinct from that which binds tRNA(Tyr). This RNA binding surface provides an extended scaffold for the phosphodiester backbone of the conserved catalytic core of the intron RNA, allowing the protein to promote the splicing of a wide variety of group I introns. The group I intron-binding surface includes three small insertions and additional structural adaptations relative to non-splicing bacterial TyrRSs, indicating a multistep adaptation for splicing function. The co-crystal structure provides insight into how CYT-18 promotes group I intron splicing, how it evolved to have this function, and how proteins could have incrementally replaced RNA structures during the transition from an RNA world to an RNP world.     

香港对新移民的管理和安置

与复杂的跨国网络与跨界互动相比,公民身份却划分了清晰的边界。香港回归中国主权后,对其公民身份的类别划分带来了极大的挑战。依照香港基本法中对居留权的定义,很大一部分——近一百六十七万人——可以享有这个权利,反映出香港与内地的跨界社会关系有着复杂历史。尽管香港与内地的社会和经济高度统一,但其边界仍然严格限制了人口从内地向香港流动。这种既统一又分离的状况导致了一种复杂的对立,部分地反映在关于居留权的争论。即使那些已经成功移民香港的内地居民也面临着各种挑战,其中最严峻的是怎样在香港这样一个住房价格最高的城市中获得可以负担的住所。因为新移民无法申请公营房屋,但这些房屋却占香港房屋总数的一半。而其私人住房的价格又是世界上最贵的。     

Complexity, Networks, and Non-Uniqueness

The aim of the paper is to introduce some of the history and key concepts of network science to a philosophical audience, and to highlight a crucial—and often problematic—presumption that underlies the network approach to complex systems. Network scientists often talk of “the structure” of a given complex system or phenomenon, which encourages the view that there is a unique and privileged structure inherent to the system, and that the aim of a network model is to delineate this structure. I argue that this sort of naïve realism about structure is not a coherent or plausible position, especially given the multiplicity of types of entities and relations that can feature as nodes and links in complex networks.     

Spruce beetle ( Dendroctonus rufipennis ) outbreak in Engelmann spruce ( Picea Engelmannii ) in central Utah, 1986-1998

Extensive Engelmann spruce ( Picea engelmannii Parry ex Engelm.) mortality caused by the spruce beetle ( Dendroctonus rufipennis Kirby) has been occurring at the southern end of the Wasatch Plateau in central Utah. This spruce beetle outbreak is the largest recorded in Utah history. An extensive ground survey was conducted in 1996 on the Manti-LaSal National Forest, Sanpete and Ferron Ranger Districts, to document mortality and impact of a major spruce beetle outbreak on post-outbreak forest composition. In 1998 the same sites were resurveyed. Survey results indicate Engelmann spruce basal area (BA) loss averaged 78% in trees ≥5 inches diameter breast height (DBH) in 1996. Ninety percent of BA ≥5 inches DBH was lost within the same sites by 1998. Tree mortality of spruce ≥5 inches DBH expressed in trees per acre (TPA) averaged 53% in 1996. In 1998 TPA ≥5 inches DBH mortality averaged 73%. Before the outbreak live Engelmann spruce BA ≥5 inches DBH averaged 99 square feet, and TPA ≥5 inches DBH averaged 97. In the sites surveyed in 1996 and resurveyed in 1998, Engelmann spruce BA ≥5 inches DBH averaged 21 and 9 square feet, and TPA ≥5 inches DBH averaged 43 and 25, respectively. Overstory tree species composition changed from stands dominated by spruce to subalpine fir. Stand ratings for potential spruce beetle outbreaks were high to mostly medium hazard pre-outbreak and medium to primarily low hazard by 1998, as a result of reduction in average spruce diameter, total basal area, and overstory spruce.     

Genetic contributions to stability and change in intelligence from childhood to old age

Understanding the determinants of healthy mental ageing is a priority for society today. So far, we know that intelligence differences show high stability from childhood to old age and there are estimates of the genetic contribution to intelligence at different ages. However, attempts to discover whether genetic causes contribute to differences in cognitive ageing have been relatively uninformative. Here we provide an estimate of the genetic and environmental contributions to stability and change in intelligence across most of the human lifetime. We used genome-wide single nucleotide polymorphism (SNP) data from 1,940 unrelated individuals whose intelligence was measured in childhood (age 11 years) and again in old age (age 65, 70 or 79 years). We use a statistical method that allows genetic (co)variance to be estimated from SNP data on unrelated individuals. We estimate that causal genetic variants in linkage disequilibrium with common SNPs account for 0.24 of the variation in cognitive ability change from childhood to old age. Using bivariate analysis, we estimate a genetic correlation between intelligence at age 11 years and in old age of 0.62. These estimates, derived from rarely available data on lifetime cognitive measures, warrant the search for genetic causes of cognitive stability and change.     

Passenger deletions generate therapeutic vulnerabilities in cancer

Inactivation of tumour-suppressor genes by homozygous deletion is a prototypic event in the cancer genome, yet such deletions often encompass neighbouring genes. We propose that homozygous deletions in such passenger genes can expose cancer-specific therapeutic vulnerabilities when the collaterally deleted gene is a member of a functionally redundant family of genes carrying out an essential function. The glycolytic gene enolase 1 (ENO1) in the 1p36 locus is deleted in glioblastoma (GBM), which is tolerated by the expression of ENO2. Here we show that short-hairpin-RNA-mediated silencing of ENO2 selectively inhibits growth, survival and the tumorigenic potential of ENO1-deleted GBM cells, and that the enolase inhibitor phosphonoacetohydroxamate is selectively toxic to ENO1-deleted GBM cells relative to ENO1-intact GBM cells or normal astrocytes. The principle of collateral vulnerability should be applicable to other passenger-deleted genes encoding functionally redundant essential activities and provide an effective treatment strategy for cancers containing such genomic events.     

Approaching a state shift in Earth's biosphere

Localized ecological systems are known to shift abruptly and irreversibly from one state to another when they are forced across critical thresholds. Here we review evidence that the global ecosystem as a whole can react in the same way and is approaching a planetary-scale critical transition as a result of human influence. The plausibility of a planetary-scale 'tipping point' highlights the need to improve biological forecasting by detecting early warning signs of critical transitions on global as well as local scales, and by detecting feedbacks that promote such transitions. It is also necessary to address root causes of how humans are forcing biological changes.