The Arabidopsis XET-related gene family: environmental and hormonal regulation of expression

Enzymes that modify cell wall components most likely play critical roles in altering size, shape, and physical properties of plant cells. Regulation of such modifying activity is expected to be important during morphogenesis and in eliciting developmental and physiological alterations that arise in response to environmental conditions. Previous work has shown that the Arabidopsis TCH4 gene encodes a xyloglucan endotransglycosylase (XET) which acts on the major hemicellulose of the plant cell wall. The expression of TCH4 is dramatically upregulated in response to several environmental stimuli (including touch, wind, darkness, heat shock, and cold shock) as well as the growth-enhancing hormones, auxin and brassinosteroids. This paper reports the presence of an extensive X ET ,related (XTR) gene family in Arabidopsis. In addition to TCH4, this family includes two previously identified genes, EXT and Meri-5, and at least five additional genes. The cDNAs of the XTR family share between 46 and 79% sequence identity and the predicted XTR proteins share from 37 to 84% identity. All eight proteins include potential N-terminal signal sequences and most have a conserved motif (DEIDFEFLG) that is also found in Bacillusβ-glucanase and may be important for enzyme activity. The members of the XTR gene family are differentially sensitive to environmental and hormonal stimuli. Magnitude and kinetics of regulation are distinct for the different genes. Differential regulation of expression of this complex gene family suggests a recruitment of related, yet distinct, cell wall-modifying enzymes that may control the properties of cell walls and tissues during development and in response to environmental cues.     

A Preclinical Murine Model of Hepatic Metastases

Numerous murine models have been developed to study human cancers and advance the understanding of cancer treatment and development. Here, a preclinical, murine pancreatic tumor model of hepatic metastases via a hemispleen injection of syngeneic murine pancreatic tumor cells is described. This model mimics many of the clinical conditions in patients with metastatic disease to the liver. Mice consistently develop metastases in the liver allowing for investigation of the metastatic process, experimental therapy testing, and tumor immunology research.     

Three Different Pathways Prevent Chromosome Segregation in the Presence of DNA Damage or Replication Stress in Budding Yeast

A surveillance mechanism, the S phase checkpoint, blocks progression into mitosis in response to DNA damage and replication stress. Segregation of damaged or incompletely replicated chromosomes results in genomic instability. In humans, the S phase checkpoint has been shown to constitute an anti-cancer barrier. Inhibition of mitotic cyclin dependent kinase (M-CDK) activity by Wee1 kinases is critical to block mitosis in some organisms. However, such mechanism is dispensable in the response to genotoxic stress in the model eukaryotic organism Saccharomyces cerevisiae. We show here that the Wee1 ortholog Swe1 does indeed inhibit M-CDK activity and chromosome segregation in response to genotoxic insults. Swe1 dispensability in budding yeast is the result of a redundant control of M-CDK activity by the checkpoint kinase Rad53. In addition, our results indicate that Swe1 is an effector of the checkpoint central kinase Mec1. When checkpoint control on M-CDK and on Pds1/securin stabilization are abrogated, cells undergo aberrant chromosome segregation.     

Malaria parasites tolerate a broad range of ionic environments and do not require host cation remodelling

Malaria parasites grow within erythrocytes, but are also free in host plasma between cycles of asexual replication. As a result, the parasite is exposed to fluctuating levels of Na⁺ and K⁺, ions assumed to serve important roles for the human pathogen, Plasmodium falciparum. We examined these assumptions and the parasite's ionic requirements by establishing continuous culture in novel sucrose‐based media. With sucrose as the primary osmoticant and K⁺ and Cl^? as the main extracellular ions, we obtained parasite growth and propagation at rates indistinguishable from those in physiological media. These conditions abolish long‐known increases in intracellular Na⁺ via parasite‐induced channels, excluding a requirement for erythrocyte cation remodelling. We also dissected Na⁺, K⁺ and Cl^? requirements and found that unexpectedly low concentrations of each ion meet the parasite's demands. Surprisingly, growth was not adversely affected by up to 148 mM K⁺, suggesting that low extracellular K⁺ is not an essential trigger for erythrocyte invasion. At the same time, merozoite egress and invasion required a threshold ionic strength, suggesting critical electrostatic interactions between macromolecules at these stages. These findings provide insights into transmembrane signalling in malaria and reveal fundamental differences between host and parasite ionic requirements.     

“The Simulacra of Morality”: Islamic Veiling, Religious Politics and the Limits of Liberalism

On December 17, 2003, French President Jaques Chirac went on television to explain the immediate necessity of passing a law recently proposed by the Stasi commission. This commission had been empowered to explore the failures of the last thirty years of French immigration policy in terms of integration. It had also been specifically instructed to investigate threats to the concept of laicite, the rigorous French version of secularism and the separation of the Church and the State. Chirac explained that, following the commission’s advice as well as that of numerous experts, he had centered on a policy to deal with these issues: We shall do so by bringing to life the principle of secularism, which is a pillar of our constitution. It expresses our wish to live together in respect, dialogue and tolerance. Secularism guarantees freedom of conscience. It protects the freedom to believe or not to believe. He then expanded upon what this freedom requires: It is the neutrality of the public sphere which enables the harmonious existence side by side of different religions. Like all freedoms, the freedom to express one’s faith can only have limits in the freedom of others, and in the compliance with rules of life in society. Religious freedom, which our country respects and protects, must not be abused, it must not call general rules into question, and it must not infringe the freedom of belief of others. Finally, Chirac, building to a rhetorical climax, came to the essence of the new law which had provoked so much commentary around the world: In all conscience, it is my view that the wearing of clothes or of symbols which conspicuously demonstrate religious affiliations must be banned in state schools. The hypothesis which I wish to advance is that in the actual world in which we inhabit the language of morality is in the same state of grave disorder as the language of natural science is in the imaginary world which I described. What we possess are the fragments of a conceptual scheme... we posses indeed simulacra of morality... but we have lost our comprehension, both theoretical and practical, of morality.     

Crystal structure of the yeast Sac1: implications for its phosphoinositide phosphatase function

Sac family phosphoinositide (PI) phosphatases are an essential family of CX₅R(T/S)‐based enzymes, involved in numerous aspects of cellular function such as PI homeostasis, cellular signalling, and membrane trafficking. Genetic deletions of several Sac family members result in lethality in animal models and mutations of the Sac3 gene have been found in human hereditary diseases. In this study, we report the crystal structure of a founding member of this family, the Sac phosphatase domain of yeast Sac1. The 2.0 Å resolution structure shows that the Sac domain comprises of two closely packed sub‐domains, a novel N‐terminal sub‐domain and the PI phosphatase catalytic sub‐domain. The structure further shows a striking conformation of the catalytic P‐loop and a large positively charged groove at the catalytic site. These findings suggest an unusual mechanism for its dephosphorylation function. Homology structural modeling of human Fig4/Sac3 allows the mapping of several disease‐related mutations and provides a framework for the understanding of the molecular mechanisms of human diseases.     

Identification of Potent Vaccine Candidates Against Campylobacter jejuni Using Immunoinformatics Approach

Infection from Campylobacter jejuni causes intense enteritis with diarrhea, fever and abdominal pain. The peptide-based vaccine could be the best way     

Simulation of NOESY spectra of DNA segments: A new scaling procedure for iterative comparison of calculated and experimental NOE intensities

Summary A new algorithm for simulation of two-dimensional NOESY spectra of DNA segments has been developed. For any given structure, NOE intensities are calculated using the relaxation matrix approach and a new realistic procedure is suggested for 1:1 comparison of calculated and experimental intensities. The procedure involves a novel method for scaling of calculated NOE intensities to represent volumes of digitised cross peaks in NOESY spectra. A data base of fine structures of all the relevant cross peaks with Lorentzian line shapes and in-phase components, is generated in a digitised manner by two-dimensional Fourier transformation of simulated time domain data, assuming a total intensity of 1.0 for each of the cross peaks. With this procedure, it is shown that the integrated volumes of these digitised cross peaks above any given threshold scale exactly as the total intensity of the respective peaks. This procedure eliminates the repetitive generation of digitised cross peaks by two-dimensional Fourier transformation during the iterative process of structure alteration and NOE intensity calculation and thus enhances the speed of DNA structure optimization. Illustrative fits of experimental and calculated spectra obtained using the new procedure are shown.[/p]