Microbial individuality: how single-cell heterogeneity enables population level strategies.

Much of our knowledge of microbial life is only a description of average population behaviours, but modern technologies provide a more inclusive view and reveal that microbes also have individuality. It is now acknowledged that isogenic cell-to-cell heterogeneity is common across organisms and across different biological processes. This heterogeneity can be regulated and functional, rather than just reflecting tolerance to noisy biochemistry. Here, we review recent advances in our understanding of microbial heterogeneity, with an emphasis on the pervasiveness of heterogeneity, the mechanisms that sustain it, and how heterogeneity enables collective function.The research has received funding from the European Research Council under the European Union's Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement 338060. The work in the Locke laboratory is also supported by a fellowship from the Gatsby Foundation (GAT3273/GLC).This is the author accepted manuscript. The final version is available from Elsevier via http://dx.doi.org/10.1016/j.mib.2015.01.00

Frequency doubling in the cyanobacterial circadian clock

Organisms use circadian clocks to generate 24-h rhythms in gene expression. However, the clock can interact with other pathways to generate shorter period oscillations. It remains unclear how these different frequencies are generated. Here, we examine this problem by studying the coupling of the clock to the alternative sigma factor $\textit{sigC}$ in the cyanobacterium $\textit{Synechococcus elongatus}$. Using single-cell microscopy, we find that $\textit{psbAI}$, a key photosynthesis gene regulated by both $\textit{sigC}$ and the clock, is activated with two peaks of gene expression every circadian cycle under constant low light. This two-peak oscillation is dependent on $\textit{sigC}$, without which $\textit{psbAI}$ rhythms revert to one oscillatory peak per day. We also observe two circadian peaks of elongation rate, which are dependent on $\textit{sigC}$, suggesting a role for the frequency doubling in modulating growth. We propose that the two-peak rhythm in $\textit{psbAI}$ expression is generated by an incoherent feedforward loop between the clock, $\textit{sigC}$ and $\textit{psbAI}$. Modelling and experiments suggest that this could be a general network motif to allow frequency doubling of outputs.This research was made possible by the award of a European Research Council under the European Union’s Seventh Framework Programme (FP/2007-2013)/ERC Grant Agreement 338060. The work in the Locke laboratory is further supported by a fellowship from the Gatsby Foundation (GAT3272/GLC) and a Fellowship from the Human Frontier Science Program (CDA00068/2012)

Independent mobility of proteins and lipids in the plasma membrane of Escherichia coli

Biotechnology and Biological Sciences Research Council. Grant Number: BB/E009571, Oxford Centre for Integrative Systems Biology (OCISB), Engineering and Physical Science Research Council, Royal Society, Hertford College Oxfor

Factorization and resummation of s-channel single top quark production

In this paper we study the factorization and resummation of s-channel single top quark production in the Standard Model at both the Tevatron and the LHC. We show that the production cross section in the threshold limit can be factorized into a convolution of hard function, soft function and jet function via soft-collinear-effective-theory (SCET), and resummation can be performed using renormalization group equation in the momentum space resummation formalism. We find that in general, the resummation effects enhance the Next-to-Leading-Order (NLO) cross sections by about $3$ at both the Tevatron and the LHC, and significantly reduce the factorization scale dependence of the total cross section at the Tevatron, while at the LHC we find that the factorization scale dependence has not been improved, compared with the NLO results.Comment: 29 pages, 7 figures; version published in JHE

Opioid therapy for chronic non-cancer pain: guidelines for Hong Kong

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Spawning rings of exceptional points out of Dirac cones

The Dirac cone underlies many unique electronic properties of graphene and topological insulators, and its band structure--two conical bands touching at a single point--has also been realized for photons in waveguide arrays, atoms in optical lattices, and through accidental degeneracy. Deformations of the Dirac cone often reveal intriguing properties; an example is the quantum Hall effect, where a constant magnetic field breaks the Dirac cone into isolated Landau levels. A seemingly unrelated phenomenon is the exceptional point, also known as the parity-time symmetry breaking point, where two resonances coincide in both their positions and widths. Exceptional points lead to counter-intuitive phenomena such as loss-induced transparency, unidirectional transmission or reflection, and lasers with reversed pump dependence or single-mode operation. These two fields of research are in fact connected: here we discover the ability of a Dirac cone to evolve into a ring of exceptional points, which we call an "exceptional ring." We experimentally demonstrate this concept in a photonic crystal slab. Angle-resolved reflection measurements of the photonic crystal slab reveal that the peaks of reflectivity follow the conical band structure of a Dirac cone from accidental degeneracy, whereas the complex eigenvalues of the system are deformed into a two-dimensional flat band enclosed by an exceptional ring. This deformation arises from the dissimilar radiation rates of dipole and quadrupole resonances, which play a role analogous to the loss and gain in parity-time symmetric systems. Our results indicate that the radiation that exists in any open system can fundamentally alter its physical properties in ways previously expected only in the presence of material loss and gain

Lithic technological responses to Late Pleistocene glacial cycling at Pinnacle Point Site 5-6, South Africa

There are multiple hypotheses for human responses to glacial cycling in the Late Pleistocene, including changes in population size, interconnectedness, and mobility. Lithic technological analysis informs us of human responses to environmental change because lithic assemblage characteristics are a reflection of raw material transport, reduction, and discard behaviors that depend on hunter-gatherer social and economic decisions. Pinnacle Point Site 5-6 (PP5-6), Western Cape, South Africa is an ideal locality for examining the influence of glacial cycling on early modern human behaviors because it preserves a long sequence spanning marine isotope stages (MIS) 5, 4, and 3 and is associated with robust records of paleoenvironmental change. The analysis presented here addresses the question, what, if any, lithic assemblage traits at PP5-6 represent changing behavioral responses to the MIS 5-4-3 interglacial-glacial cycle? It statistically evaluates changes in 93 traits with no a priori assumptions about which traits may significantly associate with MIS. In contrast to other studies that claim that there is little relationship between broad-scale patterns of climate change and lithic technology, we identified the following characteristics that are associated with MIS 4: increased use of quartz, increased evidence for outcrop sources of quartzite and silcrete, increased evidence for earlier stages of reduction in silcrete, evidence for increased flaking efficiency in all raw material types, and changes in tool types and function for silcrete. Based on these results, we suggest that foragers responded to MIS 4 glacial environmental conditions at PP5-6 with increased population or group sizes, 'place provisioning', longer and/or more intense site occupations, and decreased residential mobility. Several other traits, including silcrete frequency, do not exhibit an association with MIS. Backed pieces, once they appear in the PP5-6 record during MIS 4, persist through MIS 3. Changing paleoenvironments explain some, but not all temporal technological variability at PP5-6.Social Science and Humanities Research Council of Canada; NORAM; American-Scandinavian Foundation; Fundacao para a Ciencia e Tecnologia [SFRH/BPD/73598/2010]; IGERT [DGE 0801634]; Hyde Family Foundations; Institute of Human Origins; National Science Foundation [BCS-9912465, BCS-0130713, BCS-0524087, BCS-1138073]; John Templeton Foundation to the Institute of Human Origins at Arizona State Universit

Localisation and interactions of the Vipp1 protein in cyanobacteria

Biotechnology and Biological Sciences Research Council. Grant Number: BB/G021856. Deutsche Forschungsgemeinschaft. Grant Number: FOR 929, SCHN 690/3-1. European Commission. Grant Number: FP7-PEOPLE-2009-IEF 254575. NFR. Grant Numbers: 192436, 197119. OCISB. Royal Society and Engineering and Physical Sciences Research Council. Grant Number: EP/G0061009/