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At least 127 records · Page 7Linked to original sources

HERV Modulation in Colorectal Carcinoma Patients: A Snapshot of Endogenous Retroviral Transcriptome.

Human endogenous retroviruses (HERVs) are proviral relics of infections that affected primates' germ line. Many HERV elements retain a residual capacity to encode transcripts and proteins that have been occasionally domesticated for the host physiology. In addition, HERV transcriptional modulation is of great interest to clarify the etiology of complex disorders such as cancer, even if a few studies assessed the specific HERV loci modulated in tumor tissues. In the present work, we used a transcriptomic approach to investigate the specific expression of ~3300 HERV loci in paired tumor and normal tissues of 7 colorectal cancer (CRC) patients. A total of 102 HERVs were significantly modulated in CRC, with a general tendency towards downregulation. Of note, among the 42 upregulated HERVs 23 belonged to the HERV-H group, that is the most investigated in CRC. De novo transcriptome reconstruction and qPCR validation allowed to identify a transcript from a HERV-H locus on chromosome Xp22.3 with high specific expression in CRC samples, potentially encoding for a partial Pol protein. These results provide a detailed description of HERV transcriptional variations in CRC and its interindividual variability, identifying a HERV-H transcript that deserves further investigation for its possible impact on tumor progression.

Endogenous Retroviruses↗

Snapshot imaging at 0.5 T using echo-planar techniques.

Echo-planar imaging using a magnetic field strength of 0.5 T has resulted in an improvement in image quality compared with recent images published at 0.1 T. The sensitivity of the technique to main magnetic field inhomogeneity and transient eddy currents has necessitated innovations in gradient and radiofrequency coil design. These improvements are described, and new variations in the echo-planar pulse sequence which provide better contrast and allow separate imaging of water and fat distributions are presented.

Abdomen↗

A magnetization transfer preparation scheme for snapshot FLASH imaging.

A rapid method of generating images whose contrast is dependent on the exchange of magnetization between the free and restricted proton pools is presented. The contrast obtained is similar to that obtained from T2-weighted spin-echo images. The rapid nature of the sequence means that the RF power deposition problems encountered when using magnetization transfer in conjunction with conventional imaging sequences are avoided.

Electromagnetic Phenomena↗

Snapshot MRI with T2*-weighted magnetization preparation.

A method for encoding T2*-dependent contrasts into the preparation period of magnetization-prepared ultrafast MRI sequences is demonstrated and validated. The preparation block consists of a 90 degrees---tau---90 degrees p sequence, where p is shifted by 90 degrees for successive images. By adding two such successive images in quadrature, a combined image is obtained, in which the pixel intensities depend on the incoherent intravoxel dephasing that occurred during tau in a way that is similar to the dependence of TE in a gradient-echo sequence. The method could therefore be useful for applications that require very short repetition times for good temporal resolution, together with detection of T2*-weighted contrasts, such as functional MRI in the brain.

Brain↗

A snapshot of a transition state analogue of a novel thermophilic esterase belonging to the subfamily of mammalian hormone-sensitive lipase.

EST2 is a novel thermophilic carboxylesterase, isolated and cloned from Alicyclobacillus (formerly Bacillus) acidocaldarius, which optimally hydrolyses esters with acyl chain lengths of six to eight carbon atoms at 70 degrees C. On the basis of the amino acid sequence homology, it has been classified as a member of the mammalian hormone-sensitive lipase (HSL) subfamily. The crystal structure of EST2, complexed with a sulphonyl derivative, has been determined at 2.6 A resolution by a multiple wavelength anomalous diffraction experiment on a seleno-methionine derivative. EST2 presents a canonical alpha/beta hydrolase core, shielded at the C-terminal side by a cap region built up of five helices. It contains the lipase-like catalytic triad, Ser155, His282 and Asp252, whereby the nucleophile is covalently modified. This allows an unambiguous view of the putative active site of EST2, detecting the oxyanion hole, in whose formation the amino acid sequence motif His81-Gly82-Gly83-Gly84 is involved, and the hydrophobic binding pocket for the acyl chain. The structural model here reported provides the first example of a transition state analogue of an esterase/lipase belonging to the HSL group, thus affording useful information for the design of medical inhibitors. Moreover, as the first X-ray structure of a thermophilic carboxylesterase, the comparison with its mesophilic homologue, the Brefeldin A esterase (BFAE) from Bacillus subtilis, allows the identification of putative determinants of thermal stability.

Amino Acid Sequence↗

Snapshots of protein folding. A study on the multiple transition state pathway of cytochrome c(551) from Pseudomonas aeruginosa.

Cytochrome c(551) (cyt c(551)) from Pseudomonas aeruginosa is a small protein (82 residues) that folds via a three-state pathway with the accumulation in the microsecond time-range of a compact collapsed intermediate. The presence of a single His residue, at position 16, permits the study of the refolding at pH 7.0 in the absence of miscoordination events. Here, we report on folding kinetics in the millisecond time-range as a function of urea under different pH conditions. Analysis of this process (over-and-above proline cis-trans isomerization) at pH 7.0, suggests the existence of a multiple transition state pathway in which we postulate three transition states. Taking advantage of site-directed mutagenesis we propose that the first "unfolded-like" transition state (t(1)) originates from the electrostatic properties of the collapsed state, while the second transition state (t(2)) involves the interaction between the N and C-terminal helices and is stabilized by the salt bridge between Lys10 and Glu70 ( approximately 1 kcal mol(-1)). Our results suggest that, contrary to other cytochromes c, the roll-over effect observed for cyt c(551) at low denaturant concentration can be interpreted in terms of a broad energy barrier without population of any intermediates. The third and more "native-like" transition state (M) can be associated with the breaking/formation of the Fe(3+)-Met61 bond. This strong interaction is stabilized by the hydrogen bond between Trp56 and heme propionate 17 (HP-17) as suggested by the increase in the unfolding rate at high denaturant concentration of the Trp56Phe site-directed mutant.

Acids↗

Differences in tobacco assessment and intervention practices: a regional snapshot.

BACKGROUND: This research describes tobacco attitudes and practices of health care providers in the Upper Midwest. A baseline measure of preventive practices by providers was needed to plan effective tobacco intervention education programs. METHODS: Health care providers in a 16-county region received a mailed survey regarding tobacco assessment practices, intervention practices, attitudes, skills/knowledge, barriers, and desire for tobacco education. The survey was sent to all chiropractors, dentists, nurse practitioners/physician assistants, physicians (primary care and specialist), and public health nurses in the region. A total of 51.9% (n = 614) of all providers returned usable surveys. RESULTS: Significant differences were found between provider groups on all measured concepts. Primary care physicians, nurse practitioners/physician assistants, and public health nurses were more likely than specialist physicians, dentists, and chiropractors to assess, intervene, be supportive of tobacco cessation, have skills/knowledge about cessation, perceive fewer barriers, and want further education. CONCLUSIONS: In this region, provider groups differed in tobacco use assessment and treatment. All provider groups desired education regarding tobacco intervention. Region-wide tobacco cessation educational initiatives need to take into account differences between provider groups.

Adult↗

A snapshot of the low temperature stress transcriptome of developing rice seedlings (Oryza sativa L.) via ESTs from subtracted cDNA library.

Rice (Oryza sativa L.) is sensitive to chilling particularly during early seedling development. Given the biochemical complexity of tolerance mechanisms, genetic potential for this trait depends on highly coordinated expression of many genes. We used a simple cDNA subtraction strategy to develop Expressed Sequence Tags (ESTs) that represent an important subset of cold stress-upregulated genes. The 3,084 subtracted cDNA clones represent a total of 1,967 unigenes from 1,354 singletons and 613 contigs. As expected in the developing seedlings, genes involved in basic cellular processes, i.e., metabolism, growth and development, protein synthesis, folding and destination, cellular transport, cell division and DNA replication were widely represented. Genes with stress-related and regulatory functions comprised 23.17% of the total ESTs. These categories included proteins with known function in cellular defenses against abiotic (drought, cold and salinity) and biotic (pathogen) stresses, and proteins involved in developmental and stress response signalling and transcription. Based on the types of genes represented, tolerance mechanisms rely on precise integration of developmental processes with stress-related responses. A large fraction of the ESTs (38.7%) represents unknown proteins. This EST library is a rich source of cold stress-related genes, and supplements for other publicly available libraries for comprehensive analysis of the stress-response transcriptome.

Cold Temperature↗

Intestinal gluten sensitivity: snapshots of an unusual autoimmune-like disease.

Gluten-sensitive disease is activated in genetically susceptible individuals by the ingestion of wheat protein (gluten). Breakdown in normal tolerogenic processes to dietary gluten is likely to play a primary pathogenic role. The disease is characterized by several autoimmune-type features and provides a model for studying autoimmune processes. A recent meeting emphasized the need for a clearer picture of the molecular interactions between disease triggering agents, molecules of the immune system and other products of disease susceptibility genes.

Autoimmune Diseases↗

Snapshots of membrane-translocating proteins.

To learn about the molecular mechanism of protein translocation across the membrane of the endoplasmic reticulum (ER), the environment of nascent chains during the translocation process has been characterized using a variety of crosslinking approaches. These techniques have led to the identification of several proteins that interact transiently with the newly synthesized protein in the cytosol, during its passage across the membrane of the ER and in the ER lumen. Furthermore, lipids have been found to be in contact with membrane-inserted nascent chains, suggesting that the polypeptide enters the membrane in a protein-lipid interface.

Journal Article↗

A molecular snapshot of the metazoan 'Eve'.

A description of the molecular make-up of the ancestral multicellular animal is emerging from the growing availability of molecular biological and biochemical data gleaned from the study of modern members of ancient groups of animals. We use the distributions of classes of transcription factors, signal transduction systems and other molecular innovations among metazoan phyla to infer some of the characteristics of the first animals.

Animals↗