Thiazolides promote apoptosis in colorectal tumor cells via MAP kinase-induced Bim and Puma activation

While many anticancer therapies aim to target the death of tumor cells, sophisticated resistance mechanisms in the tumor cells prevent cell death induction. In particular enzymes of the glutathion-S-transferase (GST) family represent a well-known detoxification mechanism, which limit the effect of chemotherapeutic drugs in tumor cells. Specifically, GST of the class P1 (GSTP1-1) is overexpressed in colorectal tumor cells and renders them resistant to various drugs. Thus, GSTP1-1 has become an important therapeutic target. We have recently shown that thiazolides, a novel class of anti-infectious drugs, induce apoptosis in colorectal tumor cells in a GSTP1-1-dependent manner, thereby bypassing this GSTP1-1-mediated drug resistance. In this study we investigated in detail the underlying mechanism of thiazolide-induced apoptosis induction in colorectal tumor cells. Thiazolides induce the activation of p38 and Jun kinase, which is required for thiazolide-induced cell death. Activation of these MAP kinases results in increased expression of the pro-apoptotic Bcl-2 homologs Bim and Puma, which inducibly bind and sequester Mcl-1 and Bcl-xL leading to the induction of the mitochondrial apoptosis pathway. Of interest, while an increase in intracellular glutathione levels resulted in increased resistance to cisplatin, it sensitized colorectal tumor cells to thiazolide-induced apoptosis by promoting increased Jun kinase activation and Bim induction. Thus, thiazolides may represent an interesting novel class of anti-tumor agents by specifically targeting tumor resistance mechanisms, such as GSTP1-1.

A 4,103 marker integrated physical and comparative map of the horse genome

A comprehensive second-generation whole genome radiation hybrid (RH II), cytogenetic and comparative map of the horse genome (2n = 64) has been developed using the 5000rad horse x hamster radiation hybrid panel and fluorescence in situ hybridization (FISH). The map contains 4,103 markers (3,816 RH; 1,144 FISH) assigned to all 31 pairs of autosomes and the X chromosome. The RH maps of individual chromosomes are anchored and oriented using 857 cytogenetic markers. The overall resolution of the map is one marker per 775 kilobase pairs (kb), which represents a more than five-fold improvement over the first-generation map. The RH II incorporates 920 markers shared jointly with the two recently reported meiotic maps. Consequently the two maps were aligned with the RH II maps of individual autosomes and the X chromosome. Additionally, a comparative map of the horse genome was generated by connecting 1,904 loci on the horse map with genome sequences available for eight diverse vertebrates to highlight regions of evolutionarily conserved syntenies, linkages, and chromosomal breakpoints. The integrated map thus obtained presents the most comprehensive information on the physical and comparative organization of the equine genome and will assist future assemblies of whole genome BAC fingerprint maps and the genome sequence. It will also serve as a tool to identify genes governing health, disease and performance traits in horses and assist us in understanding the evolution of the equine genome in relation to other species.

A comparative radiation hybrid map of sheep chromosome 10

Comparative radiation hybrid (RH) maps of individual ovine chromosomes are essential to identify genes governing traits of economic importance in sheep, a livestock species for which whole genome sequence data are not yet available. The USUoRH5000 radiation hybrid panel was used to generate a RH map of sheep chromosome 10 (OAR10) with 59 markers that span 1,422 cR over an estimated 92 Mb of the chromosome, thus providing markers every 2 Mb (equivalent to every 24 cR). The markers were derived from 46 BAC end sequences (BESs), a single EST, and 12 microsatellites. Comparative analysis showed that OAR10 shares remarkable conservation of gene order along the entire length of cattle chromosome 12 and that OAR10 contains four major homologous synteny blocks, each related to segments of the homologous human chromosome 13. Extending the comparison to the horse, dog, mouse, and chicken genome showed that these blocks share conserved synteny across species.

Geological map of the Scalaro Valley – Sesia Zone (Italian Western Alps)

In the Sesia Zone (Italian Western Alps), slivers of continental crust characterised by an Alpine high-pressure imprint are intermingled with abundant mafic rocks and Mesozoic metasediments. An extensive study of the central Sesia Zone was undertaken to identify and reconstruct the lithological setting of the mono-cyclic sediments of the Scalaro Unit. A new geological map (1:5000) and schematic cross sections across the Scalaro Unit and the adjoining Eclogitic Micaschist Complex are presented here. In order to delimit the size and shape of the mono-metamorphic unit and understand its internal geometry with respect to the poly-metamorphic basement, an integrated approach was used. Linking observations and data across a range of scales, from kilometres in the field down to petrological and chronological data obtained at micrometre scale, we define for the first time the real size and internal geometry of the Scalaro Unit, as well as its large-scale structural context.

A 2-D guinea pig lung proteome map

Guinea pigs represent an important model for a number of infectious and non-infectious pulmonary diseases. The guinea pig genome has recently been sequenced to full coverage, opening up new research avenues using genomics, transcriptomics and proteomics techniques in this species. In order to further annotate the guinea pig genome and to facilitate future pulmonary proteomics in this species we constructed a 2-D guinea pig proteome map including 486 protein identifications and post translational modifications (PTMs). The map has been up-loaded to the UCD 2D-PAGE open access database (http://proteomics-portal.ucd.ie/). Transit peptides, N-terminal acetylations and other PTMs are available via Peptideatlas (ftp://PASS00619:NM455hi@ftp.peptideatlas.org/). This dataset is associated with a research article published in the Journal of Proteomics [1].

Psychomotor symptoms of schizophrenia map on the cerebral motor circuit

Schizophrenia is a devastating disorder thought to result mainly from cerebral pathology. Neuroimaging studies have provided a wealth of findings of brain dysfunction in schizophrenia. However, we are still far from understanding how particular symptoms can result from aberrant brain function. In this context, the high prevalence of motor symptoms in schizophrenia such as catatonia, neurological soft signs, parkinsonism, and abnormal involuntary movements is of particular interest. Here, the neuroimaging correlates of these motor symptoms are reviewed. For all investigated motor symptoms, neural correlates were found within the cerebral motor system. However, only a limited set of results exists for hypokinesia and neurological soft signs, while catatonia, abnormal involuntary movements and parkinsonian signs still remain understudied with neuroimaging methods. Soft signs have been associated with altered brain structure and function in cortical premotor and motor areas as well as cerebellum and thalamus. Hypokinesia is suggested to result from insufficient interaction of thalamocortical loops within the motor system. Future studies are needed to address the neural correlates of motor abnormalities in prodromal states, changes during the course of the illness, and the specific pathophysiology of catatonia, dyskinesia and parkinsonism in schizophrenia.

Al Fashir: Darfur: West Sudan Topographic Field Map Sheet 2

The present map sheet is one of six field maps of the Darfur Map Series Release II (1:250'000). The maps and the geodatabase were preparded by the Centre for Development and Environment (CDE) of the University of Berne with funding from the Swiss Federal Department of Foreign Affairs. The map is being released as a technical contribution to support the humanitarian, peace-keeping and reconstruction efforts in Darfur, Western Sudan.

Al Geneina: Darfur. West Sudan Topographic Field Map Sheet 3

The present map sheet is one of six field maps of the Darfur Map Series Release II (1:250'000). The maps and the geodatabase were preparded by the Centre for Development and Environment (CDE) of the University of Berne with funding from the Swiss Federal Department of Foreign Affairs. The map is being released as a technical contribution to support the humanitarian, peace-keeping and reconstruction efforts in Darfur, Western Sudan.

Buram: Darfur: West Sudan Topographic Field Map Sheet 6

The present map sheet is one of six field maps of the Darfur Map Series Release II (1:250'000). The maps and the geodatabase were preparded by the Centre for Development and Environment (CDE) of the University of Berne with funding from the Swiss Federal Department of Foreign Affairs. The map is being released as a technical contribution to support the humanitarian, peace-keeping and reconstruction efforts in Darfur, Western Sudan.

Hajar Banda: Darfur: West Sudan Topographic Field Map Sheet 5

The present map sheet is one of six field maps of the Darfur Map Series Release II (1:250'000). The maps and the geodatabase were preparded by the Centre for Development and Environment (CDE) of the University of Berne with funding from the Swiss Federal Department of Foreign Affairs. The map is being released as a technical contribution to support the humanitarian, peace-keeping and reconstruction efforts in Darfur, Western Sudan.

Kulbus: Darfur: West Sudan Topographical Field Map Sheet 1

The present map sheet is one of six field maps of the Darfur Map Series Release II (1:250'000). The maps and the geodatabase were preparded by the Centre for Development and Environment (CDE) of the University of Berne with funding from the Swiss Federal Department of Foreign Affairs. The map is being released as a technical contribution to support the humanitarian, peace-keeping and reconstruction efforts in Darfur, Western Sudan.

Nyala: Darfur: West Sudan Topographic Field Map Sheet 4

The present map sheet is one of six field maps of the Darfur Map Series Release II (1:250'000). The maps and the geodatabase were preparded by the Centre for Development and Environment (CDE) of the University of Berne with funding from the Swiss Federal Department of Foreign Affairs. The map is being released as a technical contribution to support the humanitarian, peace-keeping and reconstruction efforts in Darfur, Western Sudan.

Abyei: Sudan Topographic Field Map

The present map was prepared at the request of the 'Intergovernmental Authority on Development' (IGAD) for the 'Abyei Boundaries Commission', whose work is in progress as part of the implementation of the Comprehensive Peace Agreement signed on January 9, 2005. The map and the geodatabase were prepared by the Centre for Development and Environment (CDE) of the University of Berne, Switzerland, with funding from the Swiss Federal Department of Foreign Affairs. Boundaries, transliteration, settlement locations and the North-South demarcation line of 1956 drawn on this map are not authoritative and should not be considered as such.