Spatial and temporal variability of a dinoflagellate-cyanobacterium community under a complex hydrodynamical influence:a case study at the entrance to the Gulf of Finland

Variability of nutrients and pelagic biological parameters (primary production and chlorophyll a [chl a] in flagellate and cyanobacterial size fractions, nitrogen fixation, phytoplankton species abundance) was followed for 12 d in July 1996 at an anchor station at the entrance to the Gulf of Finland, Simultaneously, meso-scale physical fields and plankton distribution were mapped over the surrounding 15 x 30 km area. The study period coincided with the intense blooming of a dinoflagellate Heterocapsa triquetra Ehrenberg and cyanobacterium Aphanizomenon flos-aquae (Linné) Ralfs community. A complex background of hydrodynamical processes was observed in the study area, including downwelling, formation and development of an anticyclonic eddy and jet currents. Our hypothesis was that the horizontal scale of patches decreases and the variation of biological parameters increases when moving from the overall community level (chl a) to the size class level and further to the species level. The horizontal distribution of chl a was closely related to the different water masses, but the distribution of the 2 dominant species differed and showed high variability even within water masses. The temporal variability of the pelagic biological parameters at the anchor station (estimated by the coefficient of variation) was between 25 and 95 % and it may be explained by horizontal patchiness. The results confirmed our hypothesis by showing that the coefficient of variation of summational parameters (total chl a, total primary production) was always lower than that of parameters specific to plankton size (chl a and primary production in 20 pm size classes), functional group (diazotrophs) or species. Phytoplankton in the size range equal to or greater than 20 μm exhibited particularly pronounced variability, while the smaller size fractions were less affected

Patterns of HER-2/neu Amplification and Overexpression in Primary and Metastatic Breast Cancer

Background: Only 25% of patients with HER-2/neu-positive metastatic breast tumors respond favorably to trastuzamab (Herceptin) treatment. We hypothesized that a high failure rate of patients on trastuzamab could result if some of the metastases were HER-2 negative and these metastases ultimately determine the course of the disease. Methods: We used tissue microarrays (TMAs) containing four samples each from 196 lymph node-negative primary tumors, 196 lymph node-positive primary tumors, and three different lymph node metastases from each lymph node-positive tumor to estimate HER-2 gene amplification by fluorescence in situ hybridization (FISH) and Her-2 protein overexpression by immunohistochemistry (IHC). Results: FISH and IHC analyses gave the same result with respect to HER-2 status for 93.7% of the tissues contained in the TMAs. Tissue samples were, therefore, considered to be HER-2 positive if they were positive for either HER-2 DNA amplification or Her-2 protein expression and HER-2 negative if both FISH and IHC gave a negative result. The HER-2 status of lymph node-positive primary tumors was maintained in the majority of their metastases. For HER-2-positive primary tumors, 77% (95% confidence interval [CI] = 59% to 90%) had entirely HER-2-positive metastases, 6.5% (95% CI = 8% to 21%) had entirely HER-2-negative metastases, and 16.3% (95% CI = 5% to 34%) had a mixture of HER-2-positive and HER-2-negative metastases. For HER-2-negative primary tumors, 95% (95% CI = 88% to 98%) had metastases that were entirely negative for HER-2. Conclusions: Our data suggest that differences in HER-2 expression between primary tumors and their lymph node metastases cannot explain the high fraction of nonresponders to trastuzamab therap

Association between CMD signs and symptoms, oral parafunctions, race and sex, in 4–6-year-old African-American and Caucasian children

The associations between oral parafunctions, signs and symptoms of craniomandibular disorders (CMD), race, and sex were analysed in recordings from 203 4-6-year-old African-American and Caucasian children. Significant correlations were found between bruxism, nail biting, thumb sucking and most of the CMD signs and symptoms. There were also significant associations between most of the signs and symptoms and race, while significant association with sex was found only regarding headache, TMJ sounds and chewing pain. Significant associations were found between most CMD signs and TMJ sounds supporting the view that joint sound recordings have diagnostic value. There were also significant associations between the pain variables recorded by questionnaire and those recorded by palpation, which indicates that reliable data can be obtained by interviewing children as young as five. The results of this study support the concept that oral parafunctions have a significant role in the aetiology of CMD. The results also show that race and sex need to be considered when analysing the possible aetiological role of oral parafunctions in CMD. Longitudinal studies, beginning with low age groups are needed to better determine the role of childhood oral parafunctions in CMD aetiology.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75673/1/j.1365-2842.1995.tb00241.x.pd

Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G

Background: The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised. Methodology/Principal Findings: We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy. Conclusions/Significance: We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality

Ontology-based, Tissue MicroArray oriented, image centered tissue bank

<p>Abstract</p> <p>Background</p> <p>Tissue MicroArray technique is becoming increasingly important in pathology for the validation of experimental data from transcriptomic analysis. This approach produces many images which need to be properly managed, if possible with an infrastructure able to support tissue sharing between institutes. Moreover, the available frameworks oriented to Tissue MicroArray provide good storage for clinical patient, sample treatment and block construction information, but their utility is limited by the lack of data integration with biomolecular information.</p> <p>Results</p> <p>In this work we propose a Tissue MicroArray web oriented system to support researchers in managing bio-samples and, through the use of ontologies, enables tissue sharing aimed at the design of Tissue MicroArray experiments and results evaluation. Indeed, our system provides ontological description both for pre-analysis tissue images and for post-process analysis image results, which is crucial for information exchange. Moreover, working on well-defined terms it is then possible to query web resources for literature articles to integrate both pathology and bioinformatics data.</p> <p>Conclusions</p> <p>Using this system, users associate an ontology-based description to each image uploaded into the database and also integrate results with the ontological description of biosequences identified in every tissue. Moreover, it is possible to integrate the ontological description provided by the user with a full compliant gene ontology definition, enabling statistical studies about correlation between the analyzed pathology and the most commonly related biological processes.</p

Delineation of prognostic biomarkers in prostate cancer

Prostate cancer is the most frequently diagnosed cancer in American men(1,2). Screening for prostate-specific antigen (PSA) has led to earlier detection of prostate cancer(3), but elevated serum PSA levels may be present in non-malignant conditions such as benign prostatic hyperlasia (BPH). Characterization of gene-expression profiles that molecularly distinguish prostatic neoplasms may identify genes involved in prostate carcinogenesis, elucidate clinical biomarkers, and lead to an improved classification of prostate cancer(4-6). Using microarrays of complementary DNA, we examined gene-expression profiles of more than 50 normal and neoplastic prostate specimens and three common prostate-cancer cell lines. Signature expression profiles of normal adjacent prostate (NAP), BPH, localized prostate cancer, and metastatic, hormone-refractory prostate cancer were determined. Here we establish many associations between genes and prostate cancer. We assessed two of these genes-hepsin, a transmembrane serine protease, and pim-1, a serine/threonine kinase-at the protein level using tissue microarrays consisting of over 700 clinically stratified prostate-cancer specimens. Expression of hepsin and pim-1 proteins was significantly correlated with measures of clinical outcome. Thus, the integration of cDNA microarray, high-density tissue microarray, and linked clinical and pathology data is a powerful approach to molecular profiling of human cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62849/1/412822a0.pd