Magnetic induction mapping of magnetite chains in magnetotactic bacteria at room temperature and close to the Verwey transition using electron holography

Off-axis electron holography in the transmission electron microscope is used to record magnetic induction maps of closely spaced magnetite crystals in magnetotactic bacteria at room temperature and after cooling the sample using liquid nitrogen. The magnetic microstructure is related to the morphology and crystallography of the particles, and to interparticle interactions. At room temperature, the magnetic signal is dominated by interactions and shape anisotropy, with highly parallel and straight field lines following the axis of each chain of crystals closely. In contrast, at low temperature the magnetic induction undulates along the length of the chain. This behaviour may result from a competition between interparticle interactions and an easy axis of magnetisation that is no longer parallel to the chain axis. The quantitative nature of electron holography also allows the change in magnetisation in the crystals with temperature to be measured

Complex-based analysis of dysregulated cellular processes in cancer

Background: Differential expression analysis of (individual) genes is often used to study their roles in diseases. However, diseases such as cancer are a result of the combined effect of multiple genes. Gene products such as proteins seldom act in isolation, but instead constitute stable multi-protein complexes performing dedicated functions. Therefore, complexes aggregate the effect of individual genes (proteins) and can be used to gain a better understanding of cancer mechanisms. Here, we observe that complexes show considerable changes in their expression, in turn directed by the concerted action of transcription factors (TFs), across cancer conditions. We seek to gain novel insights into cancer mechanisms through a systematic analysis of complexes and their transcriptional regulation. Results: We integrated large-scale protein-interaction (PPI) and gene-expression datasets to identify complexes that exhibit significant changes in their expression across different conditions in cancer. We devised a log-linear model to relate these changes to the differential regulation of complexes by TFs. The application of our model on two case studies involving pancreatic and familial breast tumour conditions revealed: (i) complexes in core cellular processes, especially those responsible for maintaining genome stability and cell proliferation (e.g. DNA damage repair and cell cycle) show considerable changes in expression; (ii) these changes include decrease and countering increase for different sets of complexes indicative of compensatory mechanisms coming into play in tumours; and (iii) TFs work in cooperative and counteractive ways to regulate these mechanisms. Such aberrant complexes and their regulating TFs play vital roles in the initiation and progression of cancer.Comment: 22 pages, BMC Systems Biolog

The detection and photometric redshift determination of distant galaxies using SIRTF's Infrared Array Camera

We investigate the ability of the Space Infrared Telescope Facility's Infrared Array Camera to detect distant (z ~ 3)galaxies and measure their photometric redshifts. Our analysis shows that changing the original long wavelength filter specifications provides significant improvements in performance in this and other areas.Comment: 28 pages incl 12 figures; to appear in June 1999 PASP. Fig.12 replaced with corrected versio

Substrate-guided optimization of the syringolins yields potent proteasome inhibitors with activity against leukemia cell lines

Natural products that inhibit the proteasome have been fruitful starting points for the development of drug candidates. Those of the syringolin family have been underexploited in this context. Using the published model for substrate mimicry by the syringolins and knowledge about the substrate preferences of the proteolytic subunits of the human proteasome, we have designed, synthesized, and evaluated syringolin analogs. As some of our analogs inhibit the activity of the proteasome with second-order rate constants 5-fold greater than that of the methyl ester of syringolin B, we conclude that the substrate mimicry model for the syringolins is valid. The improvements in in vitro potency and the activities of particular analogs against leukemia cell lines are strong bases for further development of the syringolins as anti-cancer drugs.National Institutes of Health (U.S.) (Grant AI-16892

Nanopore direct RNA sequencing maps the complexity of Arabidopsis mRNA processing and m6A modification

Understanding genome organization and gene regulation requires insight into RNA transcription, processing and modification. We adapted nanopore direct RNA sequencing to examine RNA from a wild-type accession of the model plant Arabidopsis thaliana and a mutant defective in mRNA methylation (m6A). Here we show that m6A can be mapped in full-length mRNAs transcriptome-wide and reveal the combinatorial diversity of cap-associated transcription start sites, splicing events, poly(A) site choice and poly(A) tail length. Loss of m6A from 3’ untranslated regions is associated with decreased relative transcript abundance and defective RNA 30 end formation. A functional consequence of disrupted m6A is a lengthening of the circadian period. We conclude that nanopore direct RNA sequencing can reveal the complexity of mRNA processing and modification in full-length single molecule reads. These findings can refine Arabidopsis genome annotation. Further, applying this approach to less well-studied species could transform our understanding of what their genomes encode

Molecular Aspects of Breast Cancer Metastasis to the Brain

Our knowledge of the biology underlying the development of brain metastases (BM) from breast cancer has improved over the last decade due to large clinical epidemiological studies, animal models of metastasis, and the use of high-resolution gene expression profiling technologies. However, there are still major gaps in our understanding of the mechanisms utilized by breast cancer cells to colonize the brain microenvironment, thus our arsenal of therapies remains relatively nonspecific, and the prognosis for breast cancer patients with BM remains poor. Additional insights into these mechanisms are necessary to facilitate the development of new preventive and curative therapeutic regimens to block this fatal disease. This paper aims to provide a general overview for the readers of what has been achieved in this field of research and its translation into clinical practice to date and to highlight exciting new areas of research that promise to inform the development of new targeted therapies for BM

Maximal surface group representations in isometry groups of classical Hermitian symmetric spaces

Higgs bundles and non-abelian Hodge theory provide holomorphic methods with which to study the moduli spaces of surface group representations in a reductive Lie group G. In this paper we survey the case in which G is the isometry group of a classical Hermitian symmetric space of non-compact type. Using Morse theory on the moduli spaces of Higgs bundles, we compute the number of connected components of the moduli space of representations with maximal Toledo invariant.Comment: v2: added due credits to the work of Burger, Iozzi and Wienhard. v3: corrected count of connected components for G=SU(p,q) (p \neq q); added due credits to the work of Xia and Markman-Xia; minor corrections and clarifications. 31 page