Empowering statistical methods for cellular and molecular biologists.

We provide guidelines for using statistical methods to analyze the types of experiments reported in cellular and molecular biology journals such as Molecular Biology of the Cell. Our aim is to help experimentalists use these methods skillfully, avoid mistakes, and extract the maximum amount of information from their laboratory work. We focus on comparing the average values of control and experimental samples. A Supplemental Tutorial provides examples of how to analyze experimental data using R software

Now the wars are over: The past, present and future of Scottish battlefields

Battlefield archaeology has provided a new way of appreciating historic battlefields. This paper provides a summary of the long history of warfare and conflict in Scotland which has given rise to a large number of battlefield sites. Recent moves to highlight the archaeological importance of these sites, in the form of Historic Scotland’s Battlefields Inventory are discussed, along with some of the problems associated with the preservation and management of these important cultural sites

Baby-Step Giant-Step Algorithms for the Symmetric Group

We study discrete logarithms in the setting of group actions. Suppose that $G$ is a group that acts on a set $S$. When $r,s \in S$, a solution $g \in G$ to $r^g = s$ can be thought of as a kind of logarithm. In this paper, we study the case where $G = S_n$, and develop analogs to the Shanks baby-step / giant-step procedure for ordinary discrete logarithms. Specifically, we compute two sets $A, B \subseteq S_n$ such that every permutation of $S_n$ can be written as a product $ab$ of elements $a \in A$ and $b \in B$. Our deterministic procedure is optimal up to constant factors, in the sense that $A$ and $B$ can be computed in optimal asymptotic complexity, and $|A|$ and $|B|$ are a small constant from $\sqrt{n!}$ in size. We also analyze randomized "collision" algorithms for the same problem

SIRT1 and SIRT3 deacetylate homologous substrates: AceCS1,2 and HMGCS1,2.

SIRT1 and SIRT3 are NAD+-dependent protein deacetylases that are evolutionarily conserved across mammals. These proteins are located in the cytoplasm/nucleus and mitochondria, respectively. Previous reports demonstrated that human SIRT1 deacetylates Acetyl-CoA Synthase 1 (AceCS1) in the cytoplasm, whereas SIRT3 deacetylates the homologous Acetyl-CoA Synthase 2 (AceCS2) in the mitochondria. We recently showed that 3-hydroxy-3-methylglutaryl CoA synthase 2 (HMGCS2) is deacetylated by SIRT3 in mitochondria, and we demonstrate here that SIRT1 deacetylates the homologous 3-hydroxy-3-methylglutaryl CoA synthase 1 (HMGCS1) in the cytoplasm. This novel pattern of substrate homology between cytoplasmic SIRT1 and mitochondrial SIRT3 suggests that considering evolutionary relationships between the sirtuins and their substrates may help to identify and understand the functions and interactions of this gene family. In this perspective, we take a first step by characterizing the evolutionary history of the sirtuins and these substrate families

Coupling biochemistry and mechanics in cell adhesion: a model for inhomogeneous stress fiber contraction

Biochemistry and mechanics are closely coupled in cell adhesion. At sites of cell-matrix adhesion, mechanical force triggers signaling through the Rho-pathway, which leads to structural reinforcement and increased contractility in the actin cytoskeleton. The resulting force acts back to the sites of adhesion, resulting in a positive feedback loop for mature adhesion. Here we model this biochemical-mechanical feedback loop for the special case when the actin cytoskeleton is organized in stress fibers, which are contractile bundles of actin filaments. Activation of myosin II molecular motors through the Rho-pathway is described by a system of reaction-diffusion equations, which are coupled into a viscoelastic model for a contractile actin bundle. We find strong spatial gradients in the activation of contractility and in the corresponding deformation pattern of the stress fiber, in good agreement with experimental findings.Comment: Revtex, 35 pages, 13 Postscript figures included, in press with New Journal of Physics, Special Issue on The Physics of the Cytoskeleto

Evaluation of a present-day climate simulation with a new coupled atmosphere-ocean model GENMOM

We present a new, non-flux corrected AOGCM, GENMOM, that combines the GENESIS version 3 atmospheric GCM (Global Environmental and Ecological Simulation of Interactive Systems) and MOM2 (Modular Ocean Model version 2) nominally at T31 resolution. We evaluate GENMOM by comparison with reanalysis products (e.g., NCEP2) and three models used in the IPCC AR4 assessment. GENMOM produces a global temperature bias of 0.6 °C. Atmospheric features such as the jet stream structure and major semi-permanent sea level pressure centers are well simulated as is the mean planetary-scale wind structure that is needed to produce the correct position of stormtracks. Most ocean surface currents are reproduced except where they are not resolvable at T31 resolution. Overall, GENMOM captures reasonably well the observed gradients and spatial distributions of annual surface temperature and precipitation and the simulations are on par with other AOGCMs. Deficiencies in the GENMOM simulations include a warm bias in the surface temperature over the southern oceans, a split in the ITCZ and weaker-than-observed overturning circulation

Measuring Affinities of Fission Yeast Spindle Pole Body Proteins in Live Cells across the Cell Cycle

AbstractCharacterizing protein-protein interactions is essential for understanding molecular mechanisms, although reproducing cellular conditions in vitro is challenging and some proteins are difficult to purify. We developed a method to measure binding to cellular structures using fission yeast cells as reaction vessels. We varied the concentrations of Sid2p and Mob1p (proteins of the septation initiation network) and measured their binding to spindle pole bodies (SPBs), the centrosome equivalent of yeast. From our measurements we infer that Sid2p and Mob1p both exist as monomeric, heterodimeric, and homodimeric species throughout the cell cycle. During interphase these species have widely different affinities for their common receptor Cdc11p on the SPB. The data support a model with a subset of Cdc11p binding the heterodimeric species with a Kd < 0.1 μM when Sid2p binds Mob1p-Cdc11p and Kd in the micromolar range when Mob1p binds Sid2p-Cdc11p. During mitosis an additional species presumed to be the phosphorylated Sid2p−Mob1p heterodimer binds SPBs with a lower affinity. Homodimers of Sid2p or Mob1p bind to the rest of Cdc11p at SPBs with lower affinity: Kds > 10 μM during interphase and somewhat stronger during mitosis. These measurements allowed us to account for the fluctuations in Sid2p binding to SPBs throughout the cell cycle