Buckling of a growing tissue and the emergence of two-dimensional patterns

The process of biological growth and the associated generation of residual stress has previously been considered as a driving mechanism for tissue buckling and pattern selection in numerous areas of biology. Here, we develop a two-dimensional thin plate theory to simulate the growth of cultured intestinal epithelial cells on a deformable substrate, with the goal of elucidating how a tissue engineer might best recreate the regular array of invaginations (crypts of Lieberkühn) found in the wall of the mammalian intestine. We extend the standard von Kármán equations to incorporate inhomogeneity in the plate’s mechanical properties and surface stresses applied to the substrate by cell proliferation. We determine numerically the configurations of a homogeneous plate under uniform cell growth, and show how tethering to an underlying elastic foundation can be used to promote higher-order buckled configurations. We then examine the independent effects of localised softening of the substrate and spatial patterning of cellular growth, demonstrating that (within a two-dimensional framework, and contrary to the predictions of one-dimensional models) growth patterning constitutes a more viable mechanism for control of crypt distribution than does material inhomogeneity

A novel mass spectrometric strategy "bEMAP" reveals Extensive O-linked protein glycosylation in Enterotoxigenic Escherichia coli

© The Author(s) 2016. The attachment of sugars to proteins via side-chain oxygen atoms (O-linked glycosylation) is seen in all three domains of life. However, a lack of widely-applicable analytical tools has restricted the study of this process, particularly in bacteria. In E. coli, only four O-linked glycoproteins have previously been characterized. Here we present a glycoproteomics technique, termed BEMAP, which is based on the beta-elimination of O-linked glycans followed by Michael-addition of a phosphonic acid derivative, and subsequent titanium dioxide enrichment. This strategy allows site-specific mass-spectrometric identification of proteins with O-linked glycan modifications in a complex biological sample. Using BEMAP we identified cell surface-associated and membrane vesicle glycoproteins from Enterotoxigenic E. coli (ETEC) and non-pathogenic E. coli K-12. We identified 618 glycosylated Serine and Threonine residues mapping to 140 proteins in ETEC, including several known virulence factors, and 34 in E. coli K-12. The two strains had 32 glycoproteins in common. Remarkably, the majority of the ETEC glycoproteins were conserved in both strains but nevertheless were only glycosylated in the pathogen. Therefore, bacterial O-linked glycosylation is much more extensive than previously thought, and is especially important to the pathogen

Will more of the same achieve malaria elimination? Results from an integrated macroeconomic epidemiological demographic model

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordThe data underlying the model framework are available from the authors on request and selected parameters are also tabulated in the methods paper,22 and from the Malaria Atlas Project http:// www.map.ox.ac.uk/Historic levels of funding have reduced the global burden of malaria in recent years. Questions remain, however, as to whether scaling up interventions, in parallel with economic growth, has made malaria elimination more likely today than previously. The consequences of “trying but failing” to eliminate malaria are also uncertain. Reduced malaria exposure decreases the acquisition of semi-immunity during childhood, a necessary phase of the immunological transition that occurs on the pathway to malaria elimination. During this transitional period, the risk of malaria resurgence increases as proportionately more individuals across all age-groups are less able to manage infections by immune response alone. We developed a robust model that integrates the effects of malaria transmission, demography, and macroeconomics in the context of Plasmodium falciparum malaria within a hyperendemic environment. We analyzed the potential for existing interventions, alongside economic development, to achieve malaria elimination. Simulation results indicate that a 2% increase in future economic growth will increase the US$5.1 billion cumulative economic burden of malaria in Ghana to US$7.2 billion, although increasing regional insecticide-treated net coverage rates by 25% will lower malaria reproduction numbers by just 9%, reduce population-wide morbidity by −0.1%, and reduce prevalence from 54% to 46% by 2034. As scaling up current malaria control tools, combined with economic growth, will be insufficient to interrupt malaria transmission in Ghana, high levels of malaria control should be maintained and investment in research and development should be increased to maintain the gains of the past decade and to minimize the risk of resurgence, as transmission dropsMedical Research Council (MRC

Forskning og udvikling i økologisk ægproduktion

Nærværende rapport er en beskrivelse og diskussion af forskningsprojekter gennemført under FØJO i årene 1996-1999. I korthed vidste forskningen følgende: Opdrætning og belægning Det har vist sig at konventionel opdræt giver en del problemer og der er anvendt en del kræfter på at belyse konsekvensen af forskellige opdrætningsmetoder, herunder lysintensitet, adgang til udeareal, opdræt på blivende sted eller flytning. Konklusionen fra disse undersøgelser er, at: Tidlig adgang til udearealet giver øget brug af udearealet senere, tendens til færre gulvæg og signifikant færre snavsede æg Opdrætning i hytte giver større kropsvægt, større ægvægt, færre gulvæg, færre snavsede æg og bedre fjerdragt end opdrætning under konventionelle forhold. Lav belægning i æglægningsperioden med 3.5 høner pr. m2 giver højere læggeprocent, bedre fodereffektivitet, tendens til færre gulvæg og signifikant færre snavsede æg samt bedre fjerdragt, dog kun hos de høner, der var opdrættet i stald Avl og selektion Avlsmaterialets kvalitet har været en vigtig del af forskningsarbejdet, dels fordi der kun er få avlsvirksomheder tilbage, der sælger afstamninger med en vis æglægningskapacitet, dels fordi disse afstamninger primært er fremavlet med sigte på burægsproduktion. Den konklusion, der kan drages af de genetiske studier er, at såfremt fjerpilningsadfærd inddrages i et passende selektionsprogram, vil et af de største velfærdsproblemer inden for ægproduktion blive løst. Parasitter Et problem, som møder den økologiske høne, er indvoldsorme. Mulighederne for at forebygge på dette område er i projektet blevet undersøgt i forskellige sammenhænge. Konklusionen er, at man må regne med, at indvoldorme altid vil være til stede i en vis udstrækning, når besætningen har adgang til udendørs arealer. Fuldstændig udryddelse er ikke mulig. I dag findes der kun konventionelle antiparasitære midler til behandling og kontrol af parasitære infektioner. Disse midler anses ikke for at være anvendelige, da tilbageholdelsestiderne er lange. På sigt bør man avlsmæssigt arbejde mod at etablere specielle racer til udendørsproduktion som er resistente mod parasitære og andre infektioner. Grovfoder Forsøg med tildeling af grovfoder har haft en positiv effekt på ægproduktion, forbrug af fuldfoder og der var en markant lavere dødelighed. Der kan iagttages mindre fjerpilning og en forbedring af fjerdragtens kvalitet, når der gives grovfoder. Endelig kunne der hvad angår tarmsundhed konstateres en øget kråseaktivitet og øget fermentering i blindtarmene samt lavere antal af coliforme bakterier, laktose negative bakterier og enterokokker. På temamødet på Forskningscenter Foulum, berettede flere landmænd om græsrodsprojekterne, og deres resultater og erfaringer er beskrevet i denne rapport. I sit afsnit vurderer Arne Bæk Jensen bl.a., at det økologiske opdræt og anvendelsen af kyllingemødre har været en succes idet: Kyllingerne har levet under forhold, som har givet en forøgelse af dyrevelfærden. Indeklimaet i opdrætsstalden har været godt som følge af et tørt gulv Energiforbruget er blevet reduceret Den tidlige prægning har haft sin virkning I æglægningsstalden sidder ca. 90 pct. af hønerne på siddepindene om natten efter ca. 14 dage Noget tyder på, at de høner, som ikke kommer på pindene om natten, også lægger deres æg på gulvet, hvor de overnatter. Hønerne på siddepindene har en bedre redesøgningsadfærd Ved indsætning ligger hønerne et pænt stykke over normen for væg

Finding 2-Edge and 2-Vertex Strongly Connected Components in Quadratic Time

We present faster algorithms for computing the 2-edge and 2-vertex strongly connected components of a directed graph, which are straightforward generalizations of strongly connected components. While in undirected graphs the 2-edge and 2-vertex connected components can be found in linear time, in directed graphs only rather simple $O(m n)$-time algorithms were known. We use a hierarchical sparsification technique to obtain algorithms that run in time $O(n^2)$. For 2-edge strongly connected components our algorithm gives the first running time improvement in 20 years. Additionally we present an $O(m^2 / \log{n})$-time algorithm for 2-edge strongly connected components, and thus improve over the $O(m n)$ running time also when $m = O(n)$. Our approach extends to k-edge and k-vertex strongly connected components for any constant k with a running time of $O(n^2 \log^2 n)$ for edges and $O(n^3)$ for vertices

The macro-economic effects of health co-benefits associated with climate change mitigation strategies

The UK government has specific targets for greenhouse gas (GHG) emission reduction to lower the risk of dangerous climate change. Strategies to reduce GHG emissions are sometimes perceived as expensive and difficult to implement but previous work has demonstrated significant potential health co-benefits from ‘Active Travel and low carbon driving’, ‘Housing Insulation/Ventilation’, and ‘Healthy Diet’ scenarios which may be attractive to policymakers. Here a Computable General Equilibrium model is used to assess the financial effects of such health co-benefits on the wider economy including changes in labour force, social security payments and healthcare costs averted. Results suggest that for all scenarios the financial impacts of the health co-benefits will be positive and increased active travel in particular is likely to make a substantial contribution, largely due to health care costs averted. Strategies to reduce GHG emissions and improve health are likely to result in substantial and increasing positive contributions to the economy which may offset some potential economic costs and thereby be seen more favourably in times of economic austerity

The impact of Covid-19, associated behaviours and policies on the UK economy: A computable general equilibrium model

This is the final version. Available on open access from Elsevier via the DOI in this record. We estimate the potential impact of COVID-19 on the United Kingdom economy, including direct disease effects, preventive public actions and associated policies. A sectoral, whole-economy macroeconomic model was linked to a population-wide epidemiological demographic model to assess the potential macroeconomic impact of COVID-19, together with policies to mitigate or suppress the pandemic by means of home quarantine, school closures, social distancing and accompanying business closures. Our simulations indicate that, assuming a clinical attack rate of 48% and a case fatality ratio of 1.5%, COVID-19 alone would impose a direct health-related economic burden of £39.6bn (1.73% of GDP) on the UK economy. Mitigation strategies imposed for 12 weeks reduce case fatalities by 29%, but the total cost to the economy is £308bn (13.5% of GDP); £66bn (2.9% of GDP) of which is attributable to labour lost from working parents during school closures, and £201bn (8.8% of GDP) of which is attributable to business closures. Suppressing the pandemic over a longer period of time may reduce deaths by 95%, but the total cost to the UK economy also increases to £668bn (29.2% of GDP), where £166bn (7.3% of GDP) is attributable to school closures and 502bn (21.9% of GDP) to business closures. Our analyses suggest Covid-19 has the potential to impose unprecedented economic costs on the UK economy, and whilst public actions are necessary to minimise mortality, the duration of school and business closures are key to determining the economic cost. The initial economic support package promised by the UK government may be proportionate to the costs of mitigating Covid-19, but without alternative measures to reduce the scale and duration of school and business closures, the economic support may be insufficient to compensate for longer term suppression of the pandemic which could generate an even greater health impact through major recession.EU Horizon 202

Adaptive introgression underlies polymorphic seasonal camouflage in snowshoe hares

Snowshoe hares (Lepus americanus) maintain seasonal camouflage by molting to a white winter coat, but some hares remain brown during the winter in regions with low snow cover. We show that cis-regulatory variation controlling seasonal expression of the Agouti gene underlies this adaptive winter camouflage polymorphism. Genetic variation at Agouti clustered by winter coat color across multiple hare and jackrabbit species, revealing a history of recurrent interspecific gene flow. Brown winter coats in snowshoe hares likely originated from an introgressed black-tailed jackrabbit allele that has swept to high frequency in mild winter environments. These discoveries show that introgression of genetic variants that underlie key ecological traits can seed past and ongoing adaptation to rapidly changing environments. (c) The Authors, Some Rights Reserved