Simulation of High-Resolution Magnetic Resonance Images on the IBM Blue Gene/L Supercomputer Using SIMRI

Medical imaging system simulators are tools that provide a means to evaluate system architecture and create artificial image sets that are appropriate for specific applications. We have modified SIMRI, a Bloch equation-based magnetic resonance image simulator, in order to successfully generate high-resolution 3D MR images of the Montreal brain phantom using Blue Gene/L systems. Results show that redistribution of the workload allows an anatomically accurate 2563 voxel spin-echo simulation in less than 5 hours when executed on an 8192-node partition of a Blue Gene/L system

Evaluation of cell culture in microfluidic chips for application in monoclonal antibody production

Microfluidic chips are useful devices for cell culture that allow cell growth under highly controlled conditions, as is required for production of therapeutic recombinant proteins. To understand the optimal conditions for growth of cells amenable of recombinant protein expression in these devices,we culturedHEK-293T cells under different microfluidic experimental conditions. The cells were cultured in polymethyl methacrylate (PMMA) and polydi-methylsiloxane (PDMS)microdevices, in the absence or presence of the cell adhesion agent poly-D-lysine. Different microchannel geometries and thicknesses, as well as the influence of the flow rate have also been tested, showing their great influence in cell adhesion and growth. Results show that the presence of poly-D-lysine improves the adhesion and viability of the cells in continuous or discontinuous flow. Moreover, the optimal adhesion of cells was observed in the corners of themicrochannels, as well as in wide channels possibly due to the decrease in the flow rate in these areas. These studies provide insight into the optimal architecture of microchannels for long-term culture of adherent cells in order to use microfluidics devices as bioreactors for monoclonal antibodies production.Fil: Peñaherrera Pazmiño, Ana Belén. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Payés, Cristian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Sierra Rodero, Marina. Universidad Tecnológica Nacional; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Vega, M.. Universidad Tecnológica Nacional; ArgentinaFil: Rosero, G.. Universidad Tecnológica Nacional; Argentina. Universidad de Buenos Aires; ArgentinaFil: Lerner, Betiana. Universidad Tecnológica Nacional; Argentina. Universidad de Buenos Aires; ArgentinaFil: Helguera, Gustavo Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Pérez, M. S.. Universidad Tecnológica Nacional; Argentina. Universidad de Buenos Aires; Argentin

Significant effects in bread-making quality associated with the gene cluster Glu-D3/Gli-D1 from the bread wheat cultivar Prointa Guazú

Seed storage proteins (gliadins and glutenins) play a key role in the determination of dough and bread-making quality in bread wheat. This is due to the interaction between high and low molecular weight glutenins subunits and gliadins, via complex inter- and intramolecular bondings. In contrast to high molecular weight glutenins, low molecular weight glutenins and gliadins analysis is difficult due to the large number of expressed subunits and coding genes. For these reasons the role of individual proteins/subunits in the determination of wheat quality is less clear. In this work we studied the effect of gene clusters Glu-A3/Gli-A1 and Glu-D3/Gli-D1 in bread-making quality parameters using 20 F4-6 families from the cross Prointa Guazú × Prointa Oasis, both cultivars carrying identical high molecular weight glutenins subunits composition and presence of 1BL/1RS wheat-rye translocation, but differing in Glu-A3/Glu-D3 low molecular weight glutenins subunits and Gli-A1/Gli-D1 gliadins patterns. ANCOVA analysis showed a significant contribution of the Glu-D3/Gli-D1 gene cluster provided by Prointa Guazú to gluten strength explained by mixograph parameters MDS and PW, and Zeleny Test. Markers tagging Prointa Guazú Glu-D3/Gli-D1 alleles are available for strong gluten selection in breeding programs

Parkinson’s Disease in a Patient with 22q11.2 Deletion Syndrome: The Relevance of Detecting Mosaicisms by Means of Cell-By-Cell Evaluation Techniques

We report the case of a male patient from an Ashkenazi Jewish ethnic group with a history of midline defects (congenital heart disease, high-arched palate and bifid uvula). At the age of 46 years, he came to our center complaining of resting tremor, and a neurological examination concluded Parkinson?s disease. As a part of his approach, genetic evaluation was performed. Fluorescence in-situ hybridization (FISH) confirmed a mosaicism of a 22q deletion in 24% of the analyzed blood cells. Also, immunohistochemical studies were performed on samples from the minor salivary glands using a SNCA antibody. Intense SNCA immunoreactive profiles were obtained for cells from the salivary glands of the patient. This is, to our knowledge, the first description of the association of amosaicism of a 22q11.2 microdeletion syndrome with Parkinson?s disease. Our findings suggest that, before excluding the involvement of the 22q11.2 deletion in the etiology of early-onset PD cases, the spectrum of evaluations should be extended to include more sensitive FISH analysis and immunohistochemical studies. The pathogenesis of early-onset PD in patients with 22q11.2 deletion syndrome remains unknown but, if elucidated, it may contribute to understanding the etiology of PD and ultimately to preventionand treatment strategies.Fil: Perandones, Claudia. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Farini, Veronica Lujan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; ArgentinaFil: Pellene, L. A. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Sáenz Farret, Michel. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Cuevas, S. M. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Micheli, Federico. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Radrizzani Helguera, Martin. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología. Centro de Estudios en Salud y Medio Ambiente; Argentin

Genetic variability for waxy genes in Argentinean bread wheat germplasm

Amylose and amylopectin are the two polysaccharides that constitute starch in bread wheat and the enzyme GBSSI (Granule-bound starch synthase I), also known as waxy protein, is responsible for amylose synthesis in storage tissues. Decrease of the amylose content in starch has been associated with the lack of waxy protein(s). In this work, different sets of PCR markers were used to characterize the genetic variability of waxy loci from 103 Argentinean bread wheat cultivars. For the Wx-A1 locus, Wx-A1a and a novel molecular allele designed Wx-A1g were detected. Wx-B1 locus showed three alleles (Wx-B1a, Wx-B1b, Wx-B1e), and Wx-D1 locus showed only the Wx-D1a allele. Novel single-locus allele specific markers for Wx-A1b, Wx-B1b and Wx- D1b null alleles were also described. To our best knowledge this is the first study focused to characterize the genetic variability for waxy genes in bread wheat cultivars from South America

Suppressing Aneuploidy-Associated Phenotypes Improves the Fitness of Trisomy 21 Cells

An abnormal number of chromosomes, or aneuploidy, accounts for most spontaneous abortions, causes developmental defects, and is associated with aging and cancer. The molecular mechanisms by which aneuploidy disrupts cellular function remain largely unknown. Here, we show that aneuploidy disrupts the morphology of the nucleus. Mutations that increase the levels of long-chain bases suppress nuclear abnormalities of aneuploid yeast independent of karyotype identity. Quantitative lipidomics indicates that long-chain bases are integral components of the nuclear membrane in yeast. Cells isolated from patients with Down syndrome also show that abnormal nuclear morphologies and increases in long-chain bases not only suppress these abnormalities but also improve their fitness. We obtained similar results with cells isolated from patients with Patau or Edward syndrome, indicating that increases in long-chain bases improve the fitness of aneuploid cells in yeast and humans. Targeting lipid biosynthesis pathways represents an important strategy to suppress nuclear abnormalities in aneuploidy-associated diseases

The lack of the TetR-like repressor gene BCG_2177c (Rv2160A) may help mycobacteria overcome intracellular redox stress and survive longer inside macrophages when surrounded by a lipid environment

Mycobacteria, like other microorganisms, survive under different environmental variations by expressing an efficient adaptive response, oriented by regulatory elements, such as transcriptional repressors of the TetR family. These repressors in mycobacteria also appear to be related to cholesterol metabolism. In this study, we have evaluated the effect of a fatty acid (oleic–palmitic–stearic)/cholesterol mixture on some phenotypic and genotypic characteristics of a tetR-mutant strain (BCG_2177c mutated gene) of M. bovis BCG, a homologous of Rv2160A of M. tuberculosis. In order to accomplish this, we have analyzed the global gene expression of this strain by RNA-seq and evaluated its neutral-lipid storage capacity and potential to infect macrophages. We have also determined the macrophage response by measuring some pro- and anti-inflammatory cytokine expressions. In comparison with wild-type microorganisms, we showed that the mutation in the BCG_2177c gene did not affect the growth of M. bovis BCG in the presence of lipids but it probably modified the structure/composition of its cell envelope. Compared to with dextrose, an overexpression of the transcriptome of the wild-type and mutant strains was observed when these mycobacteria were cultured in lipids, mainly at the exponential phase. Twelve putative intracellular redox balance maintenance genes and four others coding for putative transcriptional factors (including WhiB6 and three TetR-like) were the main elements repeatedly overexpressed when cultured in the presence of lipids. These genes belonged to the central part of what we called the “genetic lipid signature” for M. bovis BCG. We have also found that all these mycobacteria genotypic changes affected the outcome of BCG-infected macrophages, being the mutant strain most adapted to persist longer inside the host. This high persistence result was also confirmed when mutant-infected macrophages showed overexpression of the anti-inflammatory cytokine TGF-ß versus pro-inflammatory cytokines. In summary, the lack of this TetR-like repressor expression, within a lipid environment, may help mycobacteria overcome intracellular redox stress and survive longer inside their host

Hypothesis: Somatic Mosaicism and Parkinson Disease

Letter to the EditorFil: Perandones, Carlos Edgardo. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Pellene, L. A. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Giugni, J. C.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Calvo, D. S.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Raina, G. B.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Cuevas, S. M.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Mata, I. F.. University of Washington; Estados UnidosFil: Zabetian, C. P.. University of Washington; Estados UnidosFil: Caputo, Mariela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; ArgentinaFil: Corach, Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; ArgentinaFil: Micheli, Federico. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; ArgentinaFil: Radrizzani Helguera, Martin. Universidad Nacional de San Martín. Escuela de Ciencia y Tecnología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentin