Differential geometry of grassmannians and the Plucker map

Using the Plucker map between grassmannians, we study basic aspects of classic grassmannian geometries. For 'hyperbolic' grassmannian geometries, we prove some facts (for instance, that the Plucker map is a minimal isometric embedding) that were previously known in the 'elliptic' case.

The Aurora A and B kinases are up-regulated in bone marrow-derived chronic lymphocytic leukemia cells and represent potential therapeutic targets

Background The malignant B cells in chronic lymphocytic leukemia receive signals from the bone marrow and lymph node microenvironments which regulate their survival and proliferation. Characterization of these signals and the pathways that propagate them to the interior of the cell is important for the identification of novel potential targets for therapeutic intervention. Design and Methods We compared the gene expression profiles of chronic lymphocytic leukemia B cells purified from bone marrow and peripheral blood to identify genes that are induced by the bone marrow microenvironment. Two of the differentially expressed genes were further studied in cell culture experiments and in an animal model to determine whether they could represent appropriate therapeutic targets in chronic lymphocytic leukemia. Results Functional classification analysis revealed that the majority of differentially expressed genes belong to gene ontology categories related to cell cycle and mitosis. Significantly up-regulated genes in bone marrow-derived tumor cells included important cell cycle regulators, such as Aurora A and B, survivin and CDK6. Down-regulation of Aurora A and B by RNA interference inhibited proliferation of chronic lymphocytic leukemia-derived cell lines and induced low levels of apoptosis. A similar effect was observed with the Aurora kinase inhibitor VX-680 in primary chronic lymphocytic leukemia cells that were induced to proliferate by CpG-oligonucleotides and interleukin-2. Moreover, VX-680 significantly blocked leukemia growth in a mouse model of chronic lymphocytic leukemia. Conclusions Aurora A and B are up-regulated in proliferating chronic lymphocytic leukemia cells and represent potential therapeutic targets in this disease.

The Map of the Courts and the Brazilian Borders

The formation of our borders are analyzed, at first presenting the question of the demarcation line of Tordesillas and the problems that led to the abandonment of this trace to adopt a configuration thatwould deal with both the actual possession of the territory (uti possidetis) as the natural borders formed by rivers and water borders. Next, the Map of the Courts is examined, having served as the basis for the Treaty of Madrid, and it determines, actually, the current configuration of our country. An analysis is made of this cartographic document, with the aid of digital cartography, which yieldeds in the quantity of existing distortions, to modeled its trait and found out how it was built.

Double point curves for corank 2 map germs from C-2 to C-3

We characterize finite determinacy of map germs f : (C-2, 0) -> (C-3, 0) in terms of the Milnor number mu(D(f)) of the double point curve D(f) in (C-2, 0) and we provide an explicit description of the double point scheme in terms of elementary symmetric functions. Also we prove that the Whitney equisingularity of 1-parameter families of map germs f(t) : (C-2, 0) -> (C-3, 0) is equivalent to the constancy of both mu(D(f(t))) and mu(f(t)(C-2)boolean AND H) with respect to t, where H subset of C-3 is a generic plane. (C) 2011 Elsevier B.V. All rights reserved.

Inhibition of Aurora kinases enhances chemosensitivity to temozolomide and causes radiosensitization in glioblastoma cells

Glioblastoma remains one of the most devastating human malignancies, and despite therapeutic advances, there are no drugs that significantly improve the patient survival. Altered expression of the Aurora kinases was found in different malignancies, and their inhibition has been studied in cancer therapy. In this study, we analyzed the expression of Aurora A and Aurora B in glioblastoma samples and also analyzed whether the effects of Aurora kinase inhibition were associated with temozolomide or not on cell lines and primary cultures of glioblastoma. RT-PCR assays were used to determine the mRNA expression in glioblastoma tumor samples and in the cell lines. Cell proliferation was measured by XTT assay, and apoptosis was determined by flow cytometry. Drug combination analyses were made based in Chou-Talalay method. Gamma radiation for clonogenic survival used the doses of 2, 4 and 6 Gy. Changes in Aurora B level were assessed by Western blot analysis. Aurora A and B were expressed in glioblastoma samples as well as in the glioblastoma cell lines (n = 6). Moreover, ZM447439, a selective Aurora kinase inhibitor, decreased the proliferation separately and synergistically with temozolomide in primary cultures and cell lines of glioblastoma. ZM also enhanced the effects of radiation on the two cell lines studied (U343 and U251), mainly when associated with TMZ in U343 cells. Treatment with ZM induced apoptotic cell death and diminished Aurora B protein level. These data suggest that Aurora kinase inhibition may be a target for glioblastoma treatment and could be used as adjuvant to chemo- and radiotherapy.

Auditory brainstem implant outcomes and MAP parameters: Report of experiences in adults and children

The auditory brainstem implant (ABI) was first developed to help neurofibromatosis type 2 patients. Recently, its use has been recently extended to adults with non-tumor etiologies and children with profound hearing loss who were not candidates for a cochlear implant (Cl). Although the results has been extensively reported, the stimulation parameters involved behind the outcomes have received less attention. Objective: The aim of this study is to describe the audiologic outcomes and the MAP parameters in ABI adults and children at our center. Methods: Retrospective chart review. Five adults and four children were implanted with the ABI24M from September 2005 to June 2009. In the adult patients, four had Neurofibromatosis type 2, and one had postmeningitic deafness with complete ossification of both cochleae. Three of the children had cochlear malformation or dysplasia, and one had complete ossified cochlea due to meningitis. Map parameters as well as the intraoperative electrical auditory brainstem responses were collected. Evaluation was performed with at least six months of device use and included free-field hearing thresholds, speech perception tests in the adult patients and for the children, the Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) and (ESP) were used to evaluate the development of auditory skills, besides the MUSS to evaluate. Results: The number of active electrodes that did not cause any non-auditory sensation varied from three to nineteen. All of them were programmed with SPEAK strategy, and the pulse widths varied from 100 to 300 mu s. Free-field thresholds with warble tones varied from very soft auditory sensation of 70 dBHL at 250 Hz to a pure tone average of 45 dBHL. Speech perception varied from none to 60% open-set recognition of sentences in silence in the adult population and from no auditory sensation at all to a slight improvement in the IT-MAIS/MAIS scores. Conclusion: We observed that ABI may be a good option for offering some hearing attention to both adults and children. In children, the results might not be enough to ensure oral language development. Programming the speech processor in children demands higher care to the audiologist. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

Assessment of SNPs for linkage mapping in Eucalyptus: construction of a consensus SNP/microsatellite map from two unrelated pedigrees

Financial support. Brazilian Ministry of Science and Technology (CNPq Grant 577047-2008-6), FAP-DF NEXTREE Grant 193.000.570/2009 and EMBRAPA Macroprogram 2 project grant 02.07.01.004.

Functional characterisation of the non-essential protein kinases and phosphatases regulating Aspergillus nidulans hydrolytic enzyme production

Abstract Background Despite recent advances in the understanding of lignocellulolytic enzyme regulation, less is known about how different carbon sources are sensed and the signaling cascades that result in the adaptation of cellular metabolism and hydrolase secretion. Therefore, the role played by non-essential protein kinases (NPK) and phosphatases (NPP) in the sensing of carbon and/or energetic status was investigated in the model filamentous fungus Aspergillus nidulans. Results Eleven NPKs and seven NPPs were identified as being involved in cellulase, and in some cases also hemicellulase, production in A. nidulans. The regulation of CreA-mediated carbon catabolite repression (CCR) in the parental strain was determined by fluorescence microscopy, utilising a CreA: GFP fusion protein. The sensing of phosphorylated glucose, via the RAS signalling pathway induced CreA repression, while carbon starvation resulted in derepression. Growth on cellulose represented carbon starvation and derepressing conditions. The involvement of the identified NPKs in the regulation of cellulose-induced responses and CreA derepression was assessed by genome-wide transcriptomics (GEO accession 47810). CreA:GFP localisation and the restoration of endocellulase activity via the introduction of the ∆creA mutation, was assessed in the NPK-deficient backgrounds. The absence of either the schA or snfA kinase dramatically reduced cellulose-induced transcriptional responses, including the expression of hydrolytic enzymes and transporters. The mechanism by which these two NPKs controlled gene transcription was identified, as the NPK-deficient mutants were not able to unlock CreA-mediated carbon catabolite repression under derepressing conditions, such as carbon starvation or growth on cellulose. Conclusions Collectively, this study identified multiple kinases and phosphatases involved in the sensing of carbon and/or energetic status, while demonstrating the overlapping, synergistic roles of schA and snfA in the regulation of CreA derepression and hydrolytic enzyme production in A. nidulans. The importance of a carbon starvation-induced signal for CreA derepression, permitting transcriptional activator binding, appeared paramount for hydrolase secretion.

Canine heartworm disease in Porto Velho: first record, distribution map and occurrence of positive mosquitoes

The aim of this study was to make the first report on canine heartworm disease in the state of Rondônia and confirm its transmission in this state. Blood samples were randomly collected from 727 dogs in the city of Porto Velho. The samples were analyzed to search for microfilariae and circulating antigens, using three different techniques: optical microscopy on thick blood smears stained with Giemsa; immunochromatography; and PCR. Mosquitoes were collected inside and outside the homes of all the cases of positive dogs and were tested using PCR to search for DNA of Dirofilaria immitis. Ninety-three blood samples out of 727 (12.8%) were positive according to the immunoassay technique and none according to the thick smear method. Among the 93 positive dogs, 89 (95.7%) were born in Porto Velho. No difference in the frequency of infection was observed between dogs raised indoors and in the yard. PCR on the mosquitoes resulted in only one positive pool. This result shows that the transmission of canine heartworm disease is occurring in the city of Porto Velho and that there is moderate prevalence among the dogs. The techniques of immunochromatography and PCR were more effective for detecting canine heartworm than thick blood smears. The confirmation of canine heartworm disease transmission in Porto Velho places this disease in the ranking for differential diagnosis of pulmonary nodules in humans in Rondônia.

Dense disparity map estimation respecting image discontinuities

[EN] We present an energy based approach to estimate a dense disparity map from a set of two weakly calibrated stereoscopic images while preserving its discontinuities resulting from image boundaries. We first derive a simplified expression for the disparity that allows us to estimate it from a stereo pair of images using an energy minimization approach. We assume that the epipolar geometry is known, and we include this information in the energy model. Discontinuities are preserved by means of a regularization term based on the Nagel-Enkelmann operator. We investigate the associated Euler-Lagrange equation of the energy functional, and we approach the solution of the underlying partial differential equation (PDE) using a gradient descent method The resulting parabolic problem has a unique solution. In order to reduce the risk to be trapped within some irrelevant local minima during the iterations, we use a focusing strategy based on a linear scalespace. Experimental results on both synthetic and real images arere presented to illustrate the capabilities of this PDE and scale-space based method.

Regulation of SRC-3 localization and dynamics by phosphorylation during ERα-dependent transcriptional activation

Transcription is controlled by promoter-selective transcriptional factors (TFs), which bind to cis-regulatory enhancers elements, termed hormone response elements (HREs), in a specific subset of genes. Regulation by these factors involves either the recruitment of coactivators or corepressors and direct interaction with the basal transcriptional machinery (1). Hormone-activated nuclear receptors (NRs) are well characterized transcriptional factors (2) that bind to the promoters of their target genes and recruit primary and secondary coactivator proteins which possess many enzymatic activities required for gene expression (1,3,4). In the present study, using single-cell high-resolution fluorescent microscopy and high throughput microscopy (HTM) coupled to computational imaging analysis, we investigated transcriptional regulation controlled by the estrogen receptor alpha (ERalpha), in terms of large scale chromatin remodeling and interaction with the associated coactivator SRC-3 (Steroid Receptor Coactivator-3), a member of p160 family (28) primary coactivators. ERalpha is a steroid-dependent transcriptional factor (16) that belongs to the NRs superfamily (2,3) and, in response to the hormone 17-ß estradiol (E2), regulates transcription of distinct target genes involved in development, puberty, and homeostasis (8,16). ERalpha spends most of its lifetime in the nucleus and undergoes a rapid (within minutes) intranuclear redistribution following the addition of either agonist or antagonist (17,18,19). We designed a HeLa cell line (PRL-HeLa), engineered with a chromosomeintegrated reporter gene array (PRL-array) containing multicopy hormone response-binding elements for ERalpha that are derived from the physiological enhancer/promoter region of the prolactin gene. Following GFP-ER transfection of PRL-HeLa cells, we were able to observe in situ ligand dependent (i) recruitment to the array of the receptor and associated coregulators, (ii) chromatin remodeling, and (iii) direct transcriptional readout of the reporter gene. Addition of E2 causes a visible opening (decondensation) of the PRL-array, colocalization of RNA Polymerase II, and transcriptional readout of the reporter gene, detected by mRNA FISH. On the contrary, when cells were treated with an ERalpha antagonist (Tamoxifen or ICI), a dramatic condensation of the PRL-array was observed, displacement of RNA Polymerase II, and complete decreasing in the transcriptional FISH signal. All p160 family coactivators (28) colocalize with ERalpha at the PRL-array. Steroid Receptor Coactivator-3 (SRC-3/AIB1/ACTR/pCIP/RAC3/TRAM1) is a p160 family member and a known oncogenic protein (4,34). SRC-3 is regulated by a variety of posttranslational modifications, including methylation, phosphorylation, acetylation, ubiquitination and sumoylation (4,35). These events have been shown to be important for its interaction with other coactivator proteins and NRs and for its oncogenic potential (37,39). A number of extracellular signaling molecules, like steroid hormones, growth factors and cytokines, induce SRC-3 phosphorylation (40). These actions are mediated by a wide range of kinases, including extracellular-regulated kinase 1 and 2 (ERK1-2), c-Jun N-terminal kinase, p38 MAPK, and IkB kinases (IKKs) (41,42,43). Here, we report SRC-3 to be a nucleocytoplasmic shuttling protein, whose cellular localization is regulated by phosphorylation and interaction with ERalpha. Using a combination of high throughput and fluorescence microscopy, we show that both chemical inhibition (with U0126) and siRNA downregulation of the MAP/ERK1/2 kinase (MEK1/2) pathway induce a cytoplasmic shift in SRC-3 localization, whereas stimulation by EGF signaling enhances its nuclear localization by inducing phosphorylation at T24, S857, and S860, known partecipants in the regulation of SRC-3 activity (39). Accordingly, the cytoplasmic localization of a non-phosphorylatable SRC-3 mutant further supports these results. In the presence of ERalpha, U0126 also dramatically reduces: hormone-dependent colocalization of ERalpha and SRC-3 in the nucleus; formation of ER-SRC-3 coimmunoprecipitation complex in cell lysates; localization of SRC-3 at the ER-targeted prolactin promoter array (PRL-array) and transcriptional activity. Finally, we show that SRC-3 can also function as a cotransporter, facilitating the nuclear-cytoplasmic shuttling of estrogen receptor. While a wealth of studies have revealed the molecular functions of NRs and coregulators, there is a paucity of data on how these functions are spatiotemporally organized in the cellular context. Technically and conceptually, our findings have a new impact upon evaluating gene transcriptional control and mechanisms of action of gene regulators.