Purpose: Identification of tumor antigens is essential in advancing immune-based therapeutic interventions in cancer. Particularly attractive targets are those molecules that are selectively expressed by malignant cells and that are also essential for tumor progression. Experimental Design and Results: We have used a computer-based differential display analysis tool for mining of expressed sequence tag clusters in the human Unigene database and identified Brachyury as a novel tumor antigen. Brachyury, a member of the T-box transcription factor family, is a key player in mesoderm specification during embryonic development. Moreover, transcription factors that control mesoderm have been implicated in the epithelial-mesenchymal transition (EMT), which has been postulated to be a key step during tumor progression to metastasis. Reverse transcription-PCR analysis validated the in silico predictions and showed Brachyury expression in tumors of the small intestine, stomach, kidney, bladder, uterus, ovary, and testis, as well as in cell lines derived from lung, colon, and prostate carcinomas, but not in the vast majority of the normal tissues tested. An HLA-A0201epitope of human Brachyury was identified that was able to expand T lymphocytes from blood of cancer patients and normal donors with the ability to lyse Brachyury-expressing tumor cells. Conclusions: To our knowledge, this is the first demonstration that (a) a T-box transcription factor and (b) a molecule implicated in mesodermal development, i.e., EMT, can be a potential target for human T-cell^mediated cancer immunotherapy.

In our previous studies, we used global computational differential display of ESTs that belong to UNIGENE clusters and identified human sequences differentially expressed in human tumors, as well as a considerable amount of transcripts represented only in tumor-derived cDNA libraries. Most of the tumor-specific EST clusters are derived from the plurality of the tumor types originated in tissues of both ectodermal and mesodermal origin. We found that many of such tumor-specific ESTs do not contain long open reading frames and cannot be classified as protein-encoding genes. To experimentally assess patterns of expression of these EST clusters, we studied four of them in PCR experiments on Clontech MTC panels. The experimental data confirm the results obtained by in silico screening, i.e. tumor specificity of their expression. We suggest that a significant increase in the expression of non-coding RNA is a fundamental feature of cancer cells, and that such transcripts could serve as markers for the diagnosis or monitoring of human malignancies.

Human gene LOC100505644 uncharacterized LOC100505644 [Homo sapiens] (Entrez Gene ID 100505644) is abundantly expressed in tumors but weakly expressed in few normal tissues. Till now the function of this gene remains unknown. Here we identified the chromosomal borders of the transcribed region and the major splice form of the LOC100505644-specific transcript. We characterised the major regulatory motifs of the gene and its splice sites. Analysis of the secondary structure of the major transcript variant revealed a hairpin-like structure characteristic for precursor microRNAs. Comparative genomic analysis of the locus showed that it originated in primates de novo. Taken together, our data indicate that human gene LOC100505644 encodes some non-protein coding RNA, likely a microRNA. It was assigned a gene symbol ELFN1-AS1 (ELFN1 antisense RNA 1 (non-protein coding)). This gene combines features of evolutionary novelty and predominant expression in tumors.

We report here the draft genome sequence of Geotrichum candidum strain 3C, which is a filamentous yeast-like fungus that holds great promise for biotechnology. The genome was sequenced using Ion Torrent and 454 platforms. The estimated genome size was 41.4 Mb, and 14,579 protein-coding genes were predicted ab initio.

Emergence and circulation of Mycobacterium tuberculosis strains resistant to most or all first-line and second-line anti-tuberculosis drugs requires the use of new or repurposed compounds and longer treatment regimens. Molecular analysis of the isolates consecutively recovered from a patient during such long-term treatment offers an opportunity to reveal particular features of the mycobacterial adaptation to the human host. An additional interest of such a study is that these new compounds are expensive and not routinely used to treat patients with tuberculosis, even in the countries with a high burden of multidrug/extensively drugresistant tuberculosis, such as Russia.We conducted this study as part of an ongoing molecular surveillance study of M. tuberculosis in the Kaliningrad region of Russia. The M. tuberculosis isolates were recovered from sputum of an individual with tuberculosis at 1-to 2-month intervals. The patient was a permanent resident in the Kaliningrad region in northwestern Russia and was admitted to the tuberculosis hospital at the regional tuberculosis dispensary with a diagnosis of fibrocavitary tuberculosis. The first isolate was resistant to isoniazid, rifampin, streptomycin, pyrazinamide, kanamycin, capreomycin, amikacin, ofloxacin and prothionamide, i.e. the strain was

We describe the complete sequence and organization of the mitochondrial genome from a brackish-water amoeba Clydonella sawyeri (Amoebozoa, Discosea, Vannellida). The circular mitochondrial DNA of this species has 31,131 bp in length and contains 17 protein-coding genes, 2 ribosomal RNAs, 21 transfer RNAs and 13 open reading frames. Length and gene content distinguish mitochondrial genome of Clydonella sawyeri from the mitochondrial genomes of other Amoebozoa species.

Although high altitude training has been increasingly popular among endurance athletes, the molecular and cellular bases of this adaptation remain poorly understood. We aimed to define the underlying physiological changes and screen for potential biomarkers of adaptation using transcriptional profiling of whole blood. Seven elite female speed skaters were profiled on the 18th day of high-altitude adaptation. Whole blood RNA-seq before and after an intense 1 h skating bout was used to measure gene expression changes associated with exercise. In order to identify the genes specifically regulated at high altitudes, we have leveraged the data from eight previously published microarray datasets studying blood expression changes after exercise at sea level. Using cell type-specific signatures, we were able to deconvolute changes of cell type abundance from individual gene expression changes. Among these were PHOSPHO1, with a known role in erythropoiesis, and MARC1 with a role in endogenic NO metabolism. We find that platelet and erythrocyte counts uniquely respond to altitude exercise, while changes in neutrophils represent a more generic marker of intense exercise. Publicly available data from both single cell atlases and exercise-related blood profiling dramatically increases the value of whole blood RNA-seq for the dynamic evaluation of physiological changes in an athlete’s body.

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