Comparative analysis of long DNA sequences by per element information content using different contexts

BACKGROUND: Features of a DNA sequence can be found by compressing the sequence under a suitable model; good compression implies low information content. Good DNA compression models consider repetition, differences between repeats, and base distributions. From a linear DNA sequence, a compression model can produce a linear information sequence. Linear space complexity is important when exploring long DNA sequences of the order of millions of bases. Compressing a sequence in isolation will include information on self-repetition. Whereas compressing a sequence Y in the context of another X can find what new information X gives about Y. This paper presents a methodology for performing comparative analysis to find features exposed by such models. RESULTS: We apply such a model to find features across chromosomes of Cyanidioschyzon merolae. We present a tool that provides useful linear transformations to investigate and save new sequences. Various examples illustrate the methodology, finding features for sequences alone and in different contexts. We also show how to highlight all sets of self-repetition features, in this case within Plasmodium falciparum chromosome 2. CONCLUSION: The methodology finds features that are significant and that biologists confirm. The exploration of long information sequences in linear time and space is fast and the saved results are self documenting.

\u3csup\u3e1\u3c/sup\u3eH-MRS Metabolites in Adults with Down Syndrome: Effects of Dementia

To determine if proton magnetic resonance spectroscopy (1H-MRS) detect differences in dementia status in adults with Down syndrome (DS), we used 1H-MRS to measure neuronal and glial metabolites in the posterior cingulate cortex in 22 adults with DS and in 15 age- and gender-matched healthy controls. We evaluated associations between 1H-MRS results and cognition among DS participants. Neuronal biomarkers, including N-acetylaspartate (NAA) and glutamate-glutamine complex (Glx), were significantly lower in DS patients with Alzheimer\u27s should probably be changed to Alzheimer (without \u27 or s) through ms as per the new naming standard disease (DSAD) when compared to non-demented DS (DS) and healthy controls (CTL). Neuronal biomarkers therefore appear to reflect dementia status in DS. In contrast, all DS participants had significantly higher myo-inositol (MI), a putative glial biomarker, compared to CTL. Our data indicate that there may be an overall higher glial inflammatory component in DS compared to CTL prior to and possibly independent of developing dementia. When computing the NAA to MI ratio, we found that presence or absence of dementia could be distinguished in DS. NAA, Glx, and NAA/MI in all DS participants were correlated with scores from the Brief Praxis Test and the Severe Impairment Battery. 1H-MRS may be a useful diagnostic tool in future longitudinal studies to measure AD progression in persons with DS. In particular, NAA and the NAA/MI ratio is sensitive to the functional status of adults with DS, including prior to dementia

N-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human CD4+T cell responsiveness

Acknowledgments We thank Drs. Zoe Hall and Sonia Liggi of the University of Cambridge Biochemistry Department for their contributions to metabolomics analysis and data processing. Shahin Hassanzadeh of the Laboratory of Mitochondrial Biology and Metabolism for developing the PBMC RNAseq library.Matthew Rodman of the Laboratory of Mitochondrial Biology and Metabolism for preparing lean/obese samples. Dr. Duck-Yeon Lee of the NHLBI Biochemistry Core for NAGly analysis in cell culture. Special thanks to the National Institutes of Health Oxford-Cambridge Scholars Program and the International Biomedical Research Alliance for their sponsorship and support. Funding: NHLBI Division of Intramural Research (MNS – ZIA-HL005199) and the UK MRC (JLG – MR/P011705/2; UKDRI-5002; MAPUK).Peer reviewedPublisher PD

The Neural Correlates of Theory of Mindand their Role during Empathy and theGame of Chess: A functional MagneticResonance Imaging Study

Chess involves the capacity to reason iteratively about potential intentional choices of an opponent and therefore involves high levels of explicit theory of mind [ToM] (i.e. ability to infer mental states of others) alongside clear, strategic rule-based decision-making. Functional magnetic resonance imaging was used on 12 healthy male novice chess players to identify cortical regions associated with chess, ToM and empathizing. The blood-oxygenation-level-dependent (BOLD) response for chess and empathizing tasks was extracted from each ToM region. Results showed neural overlap between ToM, chess and empathizing tasks in right-hemisphere temporo-parietal junction (TPJ) [BA40], left-hemisphere superior temporal gyrus [BA22] and posterior cingulate gyrus [BA23/31]. TPJ is suggested to underlie the capacity to reason iteratively about another's internal state in a range of tasks. Areas activated by ToM and empathy included right-hemisphere orbitofrontal cortex and bilateral middle temporal gyrus: areas that become active when there is need to inhibit one's own experience when considering the internal state of another and for visual evaluation of action rationality. Results support previous findings, that ToM recruits a neural network with each region sub-serving a supporting role depending on the nature of the task itself. In contrast, a network of cortical regions primarily located within right- and left-hemisphere medial-frontal and parietal cortex, outside the internal representational network, was selectively recruited during the chess task. We hypothesize that in our cohort of novice chess players the strategy was to employ an iterative thinking pattern which in part involved mentalizing processes and recruited core ToM-related regions

Curriculum Development to Increase Minority Research Literacy for HIV Prevention Research: A CBPR Approach

Minority engagement in HIV prevention research can improve the process and products of research. Using community-based participatory research (CBPR) to develop capacity-building tools can promote community awareness of HIV prevention, clinical research, and community roles in research

Single Cell Profiling of Circulating Tumor Cells: Transcriptional Heterogeneity and Diversity from Breast Cancer Cell Lines

BACKGROUND: To improve cancer therapy, it is critical to target metastasizing cells. Circulating tumor cells (CTCs) are rare cells found in the blood of patients with solid tumors and may play a key role in cancer dissemination. Uncovering CTC phenotypes offers a potential avenue to inform treatment. However, CTC transcriptional profiling is limited by leukocyte contamination; an approach to surmount this problem is single cell analysis. Here we demonstrate feasibility of performing high dimensional single CTC profiling, providing early insight into CTC heterogeneity and allowing comparisons to breast cancer cell lines widely used for drug discovery. METHODOLOGY/PRINCIPAL FINDINGS: We purified CTCs using the MagSweeper, an immunomagnetic enrichment device that isolates live tumor cells from unfractionated blood. CTCs that met stringent criteria for further analysis were obtained from 70% (14/20) of primary and 70% (21/30) of metastatic breast cancer patients; none were captured from patients with non-epithelial cancer (n = 20) or healthy subjects (n = 25). Microfluidic-based single cell transcriptional profiling of 87 cancer-associated and reference genes showed heterogeneity among individual CTCs, separating them into two major subgroups, based on 31 highly expressed genes. In contrast, single cells from seven breast cancer cell lines were tightly clustered together by sample ID and ER status. CTC profiles were distinct from those of cancer cell lines, questioning the suitability of such lines for drug discovery efforts for late stage cancer therapy. CONCLUSIONS/SIGNIFICANCE: For the first time, we directly measured high dimensional gene expression in individual CTCs without the common practice of pooling such cells. Elevated transcript levels of genes associated with metastasis NPTN, S100A4, S100A9, and with epithelial mesenchymal transition: VIM, TGFß1, ZEB2, FOXC1, CXCR4, were striking compared to cell lines. Our findings demonstrate that profiling CTCs on a cell-by-cell basis is possible and may facilitate the application of 'liquid biopsies' to better model drug discovery

Analysis of gene expression data from non-small celllung carcinoma cell lines reveals distinct sub-classesfrom those identified at the phenotype level

Microarray data from cell lines of Non-Small Cell Lung Carcinoma (NSCLC) can be used to look for differences in gene expression between the cell lines derived from different tumour samples, and to investigate if these differences can be used to cluster the cell lines into distinct groups. Dividing the cell lines into classes can help to improve diagnosis and the development of screens for new drug candidates. The micro-array data is first subjected to quality control analysis and then subsequently normalised using three alternate methods to reduce the chances of differences being artefacts resulting from the normalisation process. The final clustering into sub-classes was carried out in a conservative manner such that subclasses were consistent across all three normalisation methods. If there is structure in the cell line population it was expected that this would agree with histological classifications, but this was not found to be the case. To check the biological consistency of the sub-classes the set of most strongly differentially expressed genes was be identified for each pair of clusters to check if the genes that most strongly define sub-classes have biological functions consistent with NSCLC

Repertoire Enhancement with Adoptively Transferred Female Lymphocytes Controls the Growth of Pre-Implanted Murine Prostate Cancer

In prostate cancer, genes encoding androgen-regulated, Y-chromosome-encoded, and tissue-specific antigens may all be overexpressed. In the adult male host, however, most high affinity T cells targeting these potential tumor rejection antigens will be removed during negative selection. In contrast, the female mature T-cell repertoire should contain abundant precursors capable of recognizing these classes of prostate cancer antigens and mediating effective anti-tumor immune responses.We find that syngeneic TRAMP-C2 prostatic adenocarcinoma cells are spontaneously rejected in female hosts. Adoptive transfer of naïve female lymphocytes to irradiated male hosts bearing pre-implanted TRAMP-C2 tumor cells slows tumor growth and mediates tumor rejection in some animals. The success of this adoptive transfer was dependent on the transfer of female CD4 T cells and independent of the presence of CD25-expressing regulatory T cells in the transferred lymphocytes. We identify in female CD4 T cells stimulated with TRAMP-C2 a dominant MHC II-restricted response to the Y-chromosome antigen DBY. Furthermore, CD8 T cell responses in female lymphocytes to the immunodominant MHC I-restricted antigen SPAS-1 are markedly increased compared to male mice. Finally, we find no exacerbation of graft-versus-host disease in either syngeneic or minor-antigen mismatched allogeneic lymphocyte adoptive transfer models by using female into male versus male into male cells.This study shows that adoptively transferred female lymphocytes, particularly CD4 T cells, can control the outgrowth of pre-implanted prostatic adenocarcinoma cells. This approach does not significantly worsen graft-versus-host responses suggesting it may be viable in the clinic. Further, enhancing the available immune repertoire with female-derived T cells may provide an excellent pool of prostate cancer reactive T cells for further augmentation by combination with either vaccination or immune regulatory blockade strategies