Long-term evolution and transmission dynamics of swine influenza A virus

Swine influenza A viruses (SwIV) cause significant economic losses in animal husbandry as well as instances of human disease and occasionally give rise to human pandemics, including that caused by the H1N1/2009 virus. The lack of systematic and longitudinal influenza surveillance in pigs has hampered attempts to reconstruct the origins of this pandemic. Most existing swine data were derived from opportunistic samples collected from diseased pigs in disparate geographical regions, not from prospective studies in defined locations, hence the evolutionary and transmission dynamics of SwIV are poorly understood. Here we quantify the epidemiological, genetic and antigenic dynamics of SwIV in Hong Kong using a data set of more than 650 SwIV isolates and more than 800 swine sera from 12?years of systematic surveillance in this region, supplemented with data stretching back 34?years. Intercontinental virus movement has led to reassortment and lineage replacement, creating an antigenically and genetically diverse virus population whose dynamics are quantitatively different from those previously observed for human influenza viruses. Our findings indicate that increased antigenic drift is associated with reassortment events and offer insights into the emergence of influenza viruses with epidemic potential in swine and humans.     

DNA primase acts as a molecular brake in DNA replication

A hallmark feature of DNA replication is the coordination between the continuous polymerization of nucleotides on the leading strand and the discontinuous synthesis of DNA on the lagging strand. This synchronization requires a precisely timed series of enzymatic steps that control the synthesis of an RNA primer, the recycling of the lagging-strand DNA polymerase, and the production of an Okazaki fragment. Primases synthesize RNA primers at a rate that is orders of magnitude lower than the rate of DNA synthesis by the DNA polymerases at the fork. Furthermore, the recycling of the lagging-strand DNA polymerase from a finished Okazaki fragment to a new primer is inherently slower than the rate of nucleotide polymerization. Different models have been put forward to explain how these slow enzymatic steps can take place at the lagging strand without losing coordination with the continuous and fast leading-strand synthesis. Nonetheless, a clear picture remains elusive. Here we use single-molecule techniques to study the kinetics of a multiprotein replication complex from bacteriophage T7 and to characterize the effect of primase activity on fork progression. We observe the synthesis of primers on the lagging strand to cause transient pausing of the highly processive leading-strand synthesis. In the presence of both leading- and lagging-strand synthesis, we observe the formation and release of a replication loop on the lagging strand. Before loop formation, the primase acts as a molecular brake and transiently halts progression of the replication fork. This observation suggests a mechanism that prevents leading-strand synthesis from outpacing lagging-strand synthesis during the slow enzymatic steps on the lagging strand.     

Mining the plasma proteome for cancer biomarkers

Systematic searches for plasma proteins that are biological indicators, or biomarkers, for cancer are underway. The difficulties caused by the complexity of biological-fluid proteomes and tissue proteomes (which contribute proteins to plasma) and by the extensive heterogeneity among diseases, subjects and levels of sample procurement are gradually being overcome. This is being achieved through rigorous experimental design and in-depth quantitative studies. The expected outcome is the development of panels of biomarkers that will allow early detection of cancer and prediction of the probable response to therapy. Achieving these objectives requires high-quality specimens with well-matched controls, reagent resources, and an efficient process to confirm discoveries through independent validation studies.     

An ancient nova shell around the dwarf nova Z Camelopardalis

Cataclysmic variables (classical novae and dwarf novae) are binary star systems in which a red dwarf transfers hydrogen-rich matter, by way of an accretion disk, to its white dwarf companion. In dwarf novae, an instability is believed to episodically dump much of the accretion disk onto the white dwarf. The liberation of gravitational potential energy then brightens these systems by up to 100-fold every few weeks or months. Thermonuclear-powered eruptions thousands of times more luminous occur in classical novae, accompanied by significant mass ejection and formation of clearly visible shells from the ejected material. Theory predicts that the white dwarfs in all dwarf novae must eventually accrete enough mass to undergo classical nova eruptions. Here we report a shell, an order of magnitude more extended than those detected around many classical novae, surrounding the prototypical dwarf nova Z Camelopardalis. The derived shell mass matches that of classical novae, and is inconsistent with the mass expected from a dwarf nova wind or a planetary nebula. The shell observationally links the prototypical dwarf nova Z Camelopardalis with an ancient nova eruption and the classical nova process.     

Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans

Hydatidiform mole (HM) is an abnormal human pregnancy with no embryo and cystic degeneration of placental villi. We report five mutations in the maternal gene NALP7 in individuals with familial and recurrent HMs. NALP7 is a member of the CATERPILLER protein family involved in inflammation and apoptosis. NALP7 is the first maternal effect gene identified in humans and is also responsible for recurrent spontaneous abortions, stillbirths and intrauterine growth retardation.     

Marine biodiversity on the Algerian Continental Shelf (Mediterranean Sea)

The Mediterranean Sea is known as a biodiversity hot spot, with 16,848 species reported. Biodiversity is higher in coastal areas and decreases with depth. However, knowledge about the southwestern sector remains scarce. For the last three decades, sampling of soft-bottom communities along the 1180 km of the shallow Algerian coast (0–136 m) has recorded 1642 macrobenthic species. There is a decreasing west–east species-richness gradient, especially for the total species richness and the amphipods. In addition, quantitative sampling in Bou Ismail Bay in summer 1988 (98 sampling sites for a total of 841 species) shows that diversity indices (i.e. species richness, >100 species for 0.2 m^?2; Shannon diversity, >6.0; and ES₅₀, >34) are among the highest for similar sand and muddy-fine sand communities in the Mediterranean Sea and the northeastern Atlantic Ocean. Bou Ismail Bay appears to have the highest species richness among Algerian bays, probably because of its variety of benthic habitats and the absence of significant pollution in this area. Monitoring must be undertaken to survey this high biodiversity, and a national strategy should be proposed to preserve high diversity zones.     

Does geographic location matter to stock return predictability?

Building on recent and growing evidence that geographic location influences information diffusion, this paper examines the relation between firm's location and the predictability of stock returns. We hypothesize that returns on a portfolio composed of firms located in central areas are more likely to follow a random walk than returns on a portfolio composed of firms located in remote areas. Using a battery of variance ratio tests, we find strong and robust support for our prediction. In particular, we show that the returns on a portfolio composed of the 500 largest urban firms follow a random walk; however, all variance ratio tests reject the random walk hypothesis for a portfolio that includes the 500 largest rural firms. Our results are robust to alternative definitions of firm's location and portfolio formation.     

Systems,Design, and Entrepreneurial Thinking: Comparative Frameworks

The philosophies of design thinking, entrepreneurial thinking, and systems thinking have widespread application in diverse fields. However, due to the inherently abstract rhetoric and lack of commonly accepted frameworks, these philosophies are often considered buzzwords and fads. This article deconstructs the rhetoric and literature from leaders of these three philosophies and identifies their fundamental tenets. A conceptual framework that captures the differences and convergences between design thinking, entrepreneurial thinking, and systems thinking is presented. A series of four case studies derived from diverse settings like healthcare, agriculture, and social networks further illustrate these interconnections. The article argues that the emergent integration of these philosophies, as captured in the fundamental tenets, presents the most compelling opportunities for the practical application of these theoretical frameworks.