A Non-Motor Microtubule Binding Site Is Essential for the High Processivity and Mitotic Function of Kinesin-8 Kif18A

BACKGROUND: Members of the kinesin-8 subfamily are plus end-directed molecular motors that accumulate at the plus-ends of kinetochore-microtubules (kt-MTs) where they regulate MT dynamics. Loss of vertebrate kinesin-8 function induces hyperstable MTs and elongated mitotic spindles accompanied by severe chromosome congression defects. It has been reported that the motility of human kinesin-8, Kif18A, is required for its accumulation at the plus tips of kt-MTs. METHODOLOGY/FINDINGS: Here, we investigate how Kif18A localizes to the plus-ends of kt-MTs. We find that Kif18A lacking its C-terminus does not accumulate on the tips of kt-MTs and fails to fulfill its mitotic function. In vitro studies reveal that Kif18A possesses a non-motor MT binding site located within its C-proximal 121 residues. Using single molecule measurements we find that Kif18A is a highly processive motor and, furthermore, that the C-terminal tail is essential for the high processivity of Kif18A. CONCLUSION/SIGNIFICANCE: These results show that Kif18A like its yeast orthologue is a highly processive motor. The ability of Kif18A to walk on MTs for a long distance without dissociating depends on a non-motor MT binding site located at the C-terminus of Kif18A. This C-proximal tail of Kif18A is essential for its plus-end accumulation and mitotic function. These findings advance our understanding of how Kif18A accumulates at the tips of kt-MTs to fulfill its function in mitosis

The effect of a regional increase in ocean surface roughness on the tropospheric circulation: a GCM experiment

The sensitivity of the atmospheric circulation to an increase in ocean surface roughness in the Southern Hemisphere storm track is investigated in a paired general circulation model experiment. Such a change in sea roughness could be induced by ocean waves generated by storms. Two extended permanent-July runs are made. One with standard sea surface roughness, the other with ten times as a large surface roughness over open sea poleward of 40-degrees-S. The regional increase in ocean surface roughness significantly modifies the tropospheric circulation in the Southern Hemisphere. The strongest effect is the reduction of tropospheric winds (by 2 m/s or 100%) above the area with increased roughness. The poleward eddy momentum flux is reduced in the upper troposphere and the meridional eddy sensible heat flux is reduced in the lower troposphere. Zonal mean and eddy kinetic energy are consistently reduced

Numerical experiments on the atmospheric response to cold equatorial Pacific conditions ("La Nina") during northern summer

The effect of cold conditions in the central and eastern Equatorial Pacific during Northern Summer is examined in a series of numerical experiments with the low resolution (T21) atmospheric general circulation model ECHAM2. Anomalous sea surface temperatures (SST) as observed in June 1988 were prescribed and the effect on the global circulation is examined. In the model atmosphere, the anomalous cold water in the Equatorial Pacific excites a strong and stable response over the tropical Central and East Pacific. From here stationary Rossby waves radiate into both hemispheres. The Northern Hemisphere wave train is weak and affects only the Northeast Pacific area; the Southern Hemisphere wave train arches from the Central Pacific over the southern tip of South America to the South Atlantic. This response is not only present in the basic anomaly experiment with the T21 GCM but also in experiments with SST anomalies confined to the tropics and with an envelope- forrnulation of the SST anomalies, in experiments with a linear model, and in high resolution (T42) model experiments. The model output is also compared to the actually observed atmospheric state in June 1988. The model simulations do not reproduce the global circulation anomalies which were observed in June 1988. The model experiments are inconclusive with respect to the question of whether the North American drought observed in summer 1988 was related to the anomalous SST conditions in the Subtropical and Tropical Pacific. An explanatory analysis with a linear model reacting to prescribed heating anomalies as well as with the high-resolution GCM indicates that the model overreacted to the equatorial SST anomalies but almost ignored the contemporaneous subtropical SST anomalies on the Southern Hemisphere

ICON-O: The Ocean Component of the ICON Earth System Model - Global simulation characteristics and local telescoping capability

Abstract We describe the ocean general circulation model ICON-O of the Max Planck Institute for Meteorology, which forms the ocean-sea ice component of the Earth system model ICON-ESM. ICON-O relies on innovative structure-preserving finite volume numerics. We demonstrate the fundamental ability of ICON-O to simulate key features of global ocean dynamics at both uniform and non-uniform resolution. Two experiments are analyzed and compared with observations, one with a nearly uniform and eddy-rich resolution of ?10?km and another with a telescoping configuration whose resolution varies smoothly from globally ?80?km to ?10?km in a focal region in the North Atlantic. Our results show first, that ICON-O on the nearly uniform grid simulates an ocean circulation that compares well with observations and second, that ICON-O in its telescope configuration is capable of reproducing the dynamics in the focal region over decadal time scales at a fraction of the computational cost of the uniform-grid simulation. The telescopic technique offers an alternative to the established regionalization approaches. It can be used either to resolve local circulation more accurately or to represent local scales that cannot be simulated globally while remaining within a global modeling framework

Harmonics of Circadian Gene Transcription in Mammals

The circadian clock is a molecular and cellular oscillator found in most mammalian tissues that regulates rhythmic physiology and behavior. Numerous investigations have addressed the contribution of circadian rhythmicity to cellular, organ, and organismal physiology. We recently developed a method to look at transcriptional oscillations with unprecedented precision and accuracy using high-density time sampling. Here, we report a comparison of oscillating transcription from mouse liver, NIH3T3, and U2OS cells. Several surprising observations resulted from this study, including a 100-fold difference in the number of cycling transcripts in autonomous cellular models of the oscillator versus tissues harvested from intact mice. Strikingly, we found two clusters of genes that cycle at the second and third harmonic of circadian rhythmicity in liver, but not cultured cells. Validation experiments show that 12-hour oscillatory transcripts occur in several other peripheral tissues as well including heart, kidney, and lungs. These harmonics are lost ex vivo, as well as under restricted feeding conditions. Taken in sum, these studies illustrate the importance of time sampling with respect to multiple testing, suggest caution in use of autonomous cellular models to study clock output, and demonstrate the existence of harmonics of circadian gene expression in the mouse

Principal-Oscillation-Pattern Analysis of Gene Expression

Principal-oscillation-pattern (POP) analysis is a multivariate and systematic technique for identifying the dynamic characteristics of a system from time-series data. In this study, we demonstrate the first application of POP analysis to genome-wide time-series gene-expression data. We use POP analysis to infer oscillation patterns in gene expression. Typically, a genomic system matrix cannot be directly estimated because the number of genes is usually much larger than the number of time points in a genomic study. Thus, we first identify the POPs of the eigen-genomic system that consists of the first few significant eigengenes obtained by singular value decomposition. By using the linear relationship between eigengenes and genes, we then infer the POPs of the genes. Both simulation data and real-world data are used in this study to demonstrate the applicability of POP analysis to genomic data. We show that POP analysis not only compares favorably with experiments and existing computational methods, but that it also provides complementary information relative to other approaches

Time-Course Analysis of Cyanobacterium Transcriptome: Detecting Oscillatory Genes

The microarray technique allows the simultaneous measurements of the expression levels of thousands of mRNAs. By mining these data one can identify the dynamics of the gene expression time series. The detection of genes that are periodically expressed is an important step that allows us to study the regulatory mechanisms associated with the circadian cycle. The problem of finding periodicity in biological time series poses many challenges. Such challenge occurs due to the fact that the observed time series usually exhibit non-idealities, such as noise, short length, outliers and unevenly sampled time points. Consequently, the method for finding periodicity should preferably be robust against such anomalies in the data. In this paper, we propose a general and robust procedure for identifying genes with a periodic signature at a given significance level. This identification method is based on autoregressive models and the information theory. By using simulated data we show that the suggested method is capable of identifying rhythmic profiles even in the presence of noise and when the number of data points is small. By recourse of our analysis, we uncover the circadian rhythmic patterns underlying the gene expression profiles from Cyanobacterium Synechocystis