Transgelin gene is frequently downregulated by promoter DNA hypermethylation in breast cancer

Tables not included in the main manuscript have been listed. Table S1. Number of probe sets affected by AZA treatment; Table S2. Comparison of significantly altered probe sets with the independent study GSE20713 Dataset; Table S3. Cancer vs. normal analysis of TAGLN mRNA in Oncomine database. (PDF 18 kb

Differential expression patterns of metastasis suppressor proteins in basal cell carcinoma

Background: Basal cell carcinomas (BCCs) are common malignant skin tumors. Despite having a significant invasion capacity, they metastasize only rarely. Our aim in this study was to detect the expression patterns of the NM23-H1, NDRG1, E-cadherin, RHOGDI2, CD82/KAI1, MKK4, and AKAP12 metastasis suppressor proteins in BCCs. Methods: A total of 96 BCC and 10 normal skin samples were included for the immunohistochemical study. Eleven frozen BCC samples were also studied by quantitative real time polymerase chain reaction (qRT-PCR) to detect the gene expression profile. Results: NM23-H1 was strongly and diffusely expressed in all types of BCC. Significant cytoplasmic expression of NDRG1 and E-cadherin was also detected. However, AKAP12 and CD82/KAI1 expression was significantly decreased. The expressions of the other proteins were somewhere between the two extremes. Similarly, qRT-PCR analysis showed down-regulation of AKAP12 and up-regulation of NM23-H1 and NDRG1 in BCC. Morphologically aggressive BCCs showed significantly higher cytoplasmic NDRG1 expression scores and lower CD82/KAI1 scores than non-aggressive BCCs. Conclusion: The relatively preserved levels of NM23-H1, NDRG1, and E-cadherin proteins may have a positive effect on the non-metastasizing features of these tumors. © 2014 The International Society of Dermatology

Biclustering models for two-mode ordinal data

The work in this paper introduces finite mixture models that can be used to simul- taneously cluster the rows and columns of two-mode ordinal categorical response data, such as those resulting from Likert scale responses. We use the popular proportional odds parameterisation and propose models which provide insights into major patterns in the data. Model-fitting is performed using the EM algorithm and a fuzzy allocation of rows and columns to corresponding clusters is obtained. The clustering ability of the models is evaluated in a simulation study and demonstrated using two real data sets

Bi-allelic JAM2 Variants Lead to Early-Onset Recessive Primary Familial Brain Calcification.

Primary familial brain calcification (PFBC) is a rare neurodegenerative disorder characterized by a combination of neurological, psychiatric, and cognitive decline associated with calcium deposition on brain imaging. To date, mutations in five genes have been linked to PFBC. However, more than 50% of individuals affected by PFBC have no molecular diagnosis. We report four unrelated families presenting with initial learning difficulties and seizures and later psychiatric symptoms, cerebellar ataxia, extrapyramidal signs, and extensive calcifications on brain imaging. Through a combination of homozygosity mapping and exome sequencing, we mapped this phenotype to chromosome 21q21.3 and identified bi-allelic variants in JAM2. JAM2 encodes for the junctional-adhesion-molecule-2, a key tight-junction protein in blood-brain-barrier permeability. We show that JAM2 variants lead to reduction of JAM2 mRNA expression and absence of JAM2 protein in patient's fibroblasts, consistent with a loss-of-function mechanism. We show that the human phenotype is replicated in the jam2 complete knockout mouse (jam2 KO). Furthermore, neuropathology of jam2 KO mouse showed prominent vacuolation in the cerebral cortex, thalamus, and cerebellum and particularly widespread vacuolation in the midbrain with reactive astrogliosis and neuronal density reduction. The regions of the human brain affected on neuroimaging are similar to the affected brain areas in the myorg PFBC null mouse. Along with JAM3 and OCLN, JAM2 is the third tight-junction gene in which bi-allelic variants are associated with brain calcification, suggesting that defective cell-to-cell adhesion and dysfunction of the movement of solutes through the paracellular spaces in the neurovascular unit is a key mechanism in CNS calcification

What are the living conditions and health status of those who don't report their migration status? a population-based study in Chile

BACKGROUND: Undocumented immigrants are likely to be missing from population databases, making it impossible to identify an accurate sampling frame in migration research. No population-based data has been collected in Chile regarding the living conditions and health status of undocumented immigrants. However, the CASEN survey (Caracterizacion Socio- Economica Nacional) asked about migration status in Chile for the first time in 2006 and provides an opportunity to set the base for future analysis of available migration data. We explored the living conditions and health of self-reported immigrants and respondents who preferred not to report their migration status in this survey. METHODS: Cross-sectional secondary analysis of CASEN survey in Chile in 2006. Outcomes: any disability, illness/accident, hospitalization/surgery, cancer/chronic condition (all binary variables); and the number of medical/emergency attentions received (count variables). Covariates: Demographics (age, sex, marital status, urban/rural, ethnicity), socioeconomic status (education level, employment status and household income), and material standard of living (overcrowding, sanitation, housing quality). Weighted regression models were estimated for each health outcome, crude and adjusted by sets of covariates, in STATA 10.0. RESULTS: About 1% of the total sample reported being immigrants and 0.7% preferred not to report their migration status (Migration Status - Missing Values; MS-MV). The MS-MV lived in more deprived conditions and reported a higher rate of health problems than immigrants. Some gender differences were observed by health status among immigrants and the MS-MV but they were not statistically significant. Regressions indicated that age, sex, SES and material factors consistently affected MS-MVs’ chance of presenting poor health and these patterns were different to those found among immigrants. Great heterogeneity in both the MS-MV and the immigrants, as indicated by wide confidence intervals, prevented the identification of other significantly associated covariates. CONCLUSION: This is the first study to look at the living conditions and health of those that preferred not to respond their migration status in Chile. Respondents that do not report their migration status are vulnerable to poor health and may represent undocumented immigrants. Surveys that fail to identify these people are likely to misrepresent the experiences of immigrants and further quantitative and qualitative research is urgently required

Prepatterning in the Stem Cell Compartment

The mechanism by which an apparently uniform population of cells can generate a heterogeneous population of differentiated derivatives is a fundamental aspect of pluripotent and multipotent stem cell behaviour. One possibility is that the environment and the differentiation cues to which the cells are exposed are not uniform. An alternative, but not mutually exclusive possibility is that the observed heterogeneity arises from the stem cells themselves through the existence of different interconvertible substates that pre-exist before the cells commit to differentiate. We have tested this hypothesis in the case of apparently homogeneous pluripotent human embryonal carcinoma (EC) stem cells, which do not follow a uniform pattern of differentiation when exposed to retinoic acid. Instead, they produce differentiated progeny that include both neuronal and non-neural phenotypes. Our results suggest that pluripotent NTERA2 stem cells oscillate between functionally distinct substates that are primed to select distinct lineages when differentiation is induced

Fuzzy cluster validation using the partition negentropy criterion

The final publication is available at Springer via http://dx.doi.org/10.1007/978-3-642-04277-5_24Proceedings of the 19th International Conference, Limassol, Cyprus, September 14-17, 2009We introduce the Partition Negentropy Criterion (PNC) for cluster validation. It is a cluster validity index that rewards the average normality of the clusters, measured by means of the negentropy, and penalizes the overlap, measured by the partition entropy. The PNC is aimed at finding well separated clusters whose shape is approximately Gaussian. We use the new index to validate fuzzy partitions in a set of synthetic clustering problems, and compare the results to those obtained by the AIC, BIC and ICL criteria. The partitions are obtained by fitting a Gaussian Mixture Model to the data using the EM algorithm. We show that, when the real clusters are normally distributed, all the criteria are able to correctly assess the number of components, with AIC and BIC allowing a higher cluster overlap. However, when the real cluster distributions are not Gaussian (i.e. the distribution assumed by the mixture model) the PNC outperforms the other indices, being able to correctly evaluate the number of clusters while the other criteria (specially AIC and BIC) tend to overestimate it.This work has been partially supported with funds from MEC BFU2006-07902/BFI, CAM S-SEM-0255-2006 and CAM/UAM project CCG08-UAM/TIC-442

Relative magnitudes of sources of uncertainty in assessing climate change impacts on water supply security for the southern Adelaide water supply system

The sources of uncertainty in projecting the impacts of climate change on runoff are increasingly well recognized; however, translating these uncertainties to urban water security has received less attention in the literature. Furthermore, runoff cannot be used as a surrogate for water supply security when studying the impacts of climate change due to the nonlinear transformations in modeling water supply and the effects of additional uncertainties, such as demand. Consequently, this study presents a scenario-based sensitivity analysis to qualitatively rank the relative contributions of major sources of uncertainty in projecting the impacts of climate change on water supply security through time. This can then be used by water authorities to guide water planning and management decisions. The southern system of Adelaide, South Australia, is used to illustrate the methodology for which water supply system reliability is examined across six greenhouse gas (GHG) emissions scenarios, seven general circulation models, six demand projections, and 1000 stochastic rainfall time series. Results indicate the order of the relative contributions of uncertainty changes through time; however, demand is always the greatest source of uncertainty and GHG emissions scenarios the least. In general, reliability decreases over the planning horizon, illustrating the need for additional water sources or demand mitigation, while increasing uncertainty with time suggests flexible management is required to ensure future supply security with minimum regret.F.L. Paton, H.R. Maier and G.C. Dand