Inverting family GH156 sialidases define an unusual catalytic motif for glycosidase action

Sialic acids are a family of related sugars that play essential roles in many biological events intimately linked to cellular recognition in both health and disease. Sialidases are therefore orchestrators of cellular biology and important therapeutic targets for viral infection. Here, we sought to define if uncharacterized sialidases would provide distinct paradigms in sialic acid biochemistry. We show that a recently discovered sialidase family, whose first member EnvSia156 was isolated from hot spring metagenomes, defines an unusual structural fold and active centre constellation, not previously described in sialidases. Consistent with an inverting mechanism, EnvSia156 reveals a His/Asp active center in which the His acts as a Bronsted acid and Asp as a Bronsted base in a single-displacement mechanism. A pre-dominantly hydrophobic aglycone site facilitates accommodation of a variety of 2-linked sialosides; a versatility that offers the potential for glycan hydrolysis across a range of biological and technological platforms

From universal service to universal connectivity

Two features of the century-old policy goal of promoting universal telephone service in the United States have been enduring. Policymakers have focused on (1) wireline telephone (and more recently, fixed-line broadband) services and (2) households. The widespread adoption of mobile telephones compels a fresh examination of this focus. We construct a new measure of universal connectivity which accounts for consumers’ choices of communications technologies and for their geographic mobility over the course of the day. This measure, in turn, compels a conceptual and empirical investigation of the determinants of mobile telephone diffusion within families. Our estimations of intra-household demand for mobile service permit us to develop simulations that estimate the economic impact of modernizing a key element of existing universal service policy (viz., the Lifeline Program) to reflect the goal of improving individual connectivity. We find that a policy expansion from a single subsidy per household to multiple subsidies per eligible household members would increase mobile subscriptions by 2.25 million and Lifeline costs by $250 million

Association of the OPRM1 Variant rs1799971 (A118G) with Non-Specific Liability to Substance Dependence in a Collaborative de novo Meta-Analysis of European-Ancestry Cohorts

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IT Outsourcing in Finnish Business

This paper reviews the characteristics and magnitude of information technology (IT) outsourcing as well as studies its labor productivity effects with a representative sample of Finnish businesses. Depending on the IT task in question, on average from one-third to two-thirds of IT has been outsourced; of the ten categories considered, the development of non-Internet business-to-business applications (e.g., EDI) is the leading activity in this respect. The various dimensions of IT outsourcing are all highly positively correlated. After controlling for industry and regional effects as well as characteristics of firms and their employees, it is found that an externally-supported computer user is about 20% more productive than an otherwise similar worker without a computer, which corresponds to about 5% output elasticity of outsourced IT; the effect of internally-supported computer use is not statistically significantly different for zero, and it is also several times smaller in magnitude. While the issues of causality, timing, self-selection, and unobserved firm heterogeneity are not fully addressed, the findings nevertheless suggest that IT outsourcing may have significant economic consequences

Habitat effects on the breeding performance of three forest-dwelling hawks

PLoS ONE 10(9): e0137877Habitat loss causes population declines, but the mechanisms are rarely known. In the European Boreal Zone, loss of old forest due to intensive forestry is suspected to cause declines in forest-dwelling raptors by reducing their breeding performance. We studied the boreal breeding habitat and habitat-associated breeding performance of the northern goshawk (Accipiter gentilis), common buzzard (Buteo buteo) and European honey buzzard (Pernis apivorus). We combined long-term Finnish bird-of-prey data with multi-source national forest inventory data at various distances (100–4000 m) around the hawk nests. We found that breeding success of the goshawk was best explained by the habitat within a 2000-m radius around the nests; breeding was more successful with increasing proportions of old spruce forest and water, and decreasing proportions of young thinning forest. None of the habitat variables affected significantly the breeding success of the common buzzard or the honey buzzard, or the brood size of any of the species. The amount of old spruce forest decreased both around goshawk and common buzzard nests and throughout southern Finland in 1992–2010. In contrast, the area of young forest increased in southern Finland but not around hawk nests. We emphasize the importance of studying habitats at several spatial and temporal scales to determine the relevant species-specific scale and to detect environmental changes. Further effort is needed to reconcile the socioeconomic and ecological functions of forests and habitat requirements of old forest specialists.Peer reviewe