cGMP-mediated signaling via cGKIalpha is required for the guidance and connectivity of sensory axons

Previous in vitro studies using cGMP or cAMP revealed a cross-talk between signaling mechanisms activated by axonal guidance receptors. However, the molecular elements modulated by cyclic nucleotides in growth cones are not well understood. cGMP is a second messenger with several distinct targets including cGMP-dependent protein kinase I (cGKI). Our studies indicated that the alpha isoform of cGKI is predominantly expressed by sensory axons during developmental stages, whereas most spinal cord neurons are negative for cGKI. Analysis of the trajectories of axons within the spinal cord showed a longitudinal guidance defect of sensory axons within the developing dorsal root entry zone in the absence of cGKI. Consequently, in cGKI-deficient mice, fewer axons grow within the dorsal funiculus of the spinal cord, and lamina-specific innervation, especially by nociceptive sensory neurons, is strongly reduced as deduced from anti-trkA staining. These axon guidance defects in cGKI-deficient mice lead to a substantial impairment in nociceptive flexion reflexes, shown using electrophysiology. In vitro studies revealed that activation of cGKI in embryonic dorsal root ganglia counteracts semaphorin 3A-induced growth cone collapse. Our studies therefore reveal that cGMP signaling is important for axonal growth in vivo and in vitro.     

Independent induction of two blue light-dependent monovalent anion transport systems in the plasma membrane of Monoraphidium braunii

In the plasma membrane of the green alga Monoraphidium braunii there are at least two monovalent anion transport systems. One of them is specific for bicarbonate. This transport system is activated by blue light and its induction is triggered by a decrease in the external CO2 concentration. The second transport system is responsible for nitrate uptake at least. This transport system is also activated by blue light and its induction occurs when there is no ammonium in the external medium. Both transport systems are synthesized independently. Hence, when M. braunii cells grow with nitrate as the only nitrogen source under high CO2, they have a nitrate transport system but lack a bicarbonate transporter. Conversely, cells grown with ammonium under low CO2, have a bicarbonate transport system but lack a nitrate transporter. Both transport systems are induced in cells irradiated with white light in the absence of a carbon source, suggesting that there may be precursors in the plasma membrane that only need the synthesis and assembly of some component(s) to become fully active. The induction of nitrate and nitrite reductases, however, only takes place when a carbon source is supplied to the cells.     

Paper2sequences: retrieval of sequences listed in a publication

Our web-based tool simplifies the often laborious procedure of retrieving a set of biosequences in a publication or webpage. As a front-end to the Bioperl toolkit, it accepts as an input a list of identifiers. They are specified in an ASCII table (copy-pasted from the publication's PDF or HTML page) and give rise to queries in multiple databases for the protein/nucleic acid data specified. Currently, GenBank, PIR (Protein Information Resource) and Swiss-Prot are supported. For any sequence accession code listed, the database can be specified and, if retrieval fails, automatic lookup for the same code in other databases can be requested. Sequence length information (if specified) and heuristic rules are used to drive the lookup if multiple protein coding sequences (CDS) are part of a single accession. Warnings are issued in cases of ambiguities and inconsistencies. An advanced option enables the user to format the output in whatever format they wish.     

Inhibition of cytosolic phospholipase A2 mRNA expression: a novel mechanism for acetylsalicylic acid-mediated growth inhibition and apoptosis in colon cancer cells

Acetylsalicylic acid (ASA) has been confirmed to inhibit proliferation and to induce apoptosis in human colorectal cancer cells in vitro. However, the mechanism by which ASA exhibits antiproliferative and proapoptotic effects in cyclooxygenase 2 (COX-2)-negative cells remains to be further elucidated. In the present study, SW480, a COX-2-negative colon cancer cell line, was treated with various concentrations of ASA (0, 2.5, 5, and 10 mM). The antiproliferative and proapoptotic effects of ASA were confirmed by MTT assay, flow cytometry of propidium iodide (PI)-stained cells, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay. After treatment with ASA, intracellular cyclic AMP (cAMP) levels were increased and the production of prostaglandin E2 (PGE2) was decreased. RT-PCR analysis revealed that treatment of ASA induced a concentration-dependent downregulation of cytosolic phospholipase A2 (cPLA2) mRNA expression in SW480 cells and also in two other colorectal cancer cell lines, Colo320 and HT-29 cells. Intracellular calcium levels were unaffected by ASA treatment. Our results indicate that the ASA-induced downregulation of cytosolic phospholipase A2 mRNA expression might be a novel mechanism for ASA-mediated growth inhibition and apoptosis in colon cancer cells.     

Further advances in the development of a data interchange standard for proteomics data

The Protein Standards Initiative (PSI) aims to define community standards for data representation in proteomics and to facilitate data comparison, exchange and verification. Significant progress was made in advancing the design and implementation of a draft standard for exchanging experimental data from proteomics experiments involving mass spectrometry at the 51st Annual Conference of the American Society for Mass Spectrometry. In collaboration with the American Society for Tests and Measurements, the PSI propose to publish this first draft at the forthcoming HUPO 2nd World Congress in Montreal, 8-11 October 2003.     

Iplt--image processing library and toolkit for the electron microscopy community

We present the foundation for establishing a modular, collaborative, integrated, open-source architecture for image processing of electron microscopy images, named iplt. It is designed around object oriented paradigms and implemented using the programming languages C++ and Python. In many aspects it deviates from classical image processing approaches. This paper intends to motivate developers within the community to participate in this on-going project. The iplt homepage can be found at http://www.iplt.org.