Novel alleles of the Transforming Growth Factor β-1 promoter and exon 1

Transforming growth factor β-1, encoded by the TGFB1 gene, is a cytokine that plays a central role in many physiologic and pathogenic processes, having pleiotropic effects on cell proliferation, differentiation, migration and survival. Regulatory activity for this gene has been demonstrated for approximately 3.0 kb between positions -2,665 and +423 from its translational start site. This region includes two promoter sites, two negative regulatory elements and two enhancers, in addition to part of the protein’s signal peptide. An important amount of polymorphism has been reported for this gene, including 17 promoter and exon 1 alleles defined on the basis or 18 polymorphisms . Polymorphism in TGFB1 has been associated to differential levels of expression of this cytokine and to genetic risk in cancer and hematopoietic stem cell (HSCT) and organ transplantation. In this report, we extend this list by presenting novel alleles formed by new polymorphic positions and a new combination of the previously described polymorphisms. These novel alleles have been found during the typing of a cohort of unrelated haematopoietic stem cell transplantation patient-donor pairs, and of healthy volunteer donors

Key determinants in building financial capability among middle schoolers with a school-based financial literacy education program

Rising in importance at various life stages, financial literacy and welfare-enhancing financial behaviors are crucial life-skills for youth to develop in their early teens. Financial capabilities could be built in schools to keep pace with today’s fast-changing and complex financial marketplace. Their financial decisions will influence their future economic well-being. This study examined the relative effectiveness of variations of a co-curricular financial literacy education program offered to eight graders of a Middle School in New England. Mixed methods were utilized first, to determine differences in program effects at improving the students’ financial literacy and changing their financial attitudes and behaviors; and second, to uncover the determinants of the outcomes in building the students’ financial capability. There were differences found in degrees of improvements in financial knowledge and financial attitudes between each one and another variant of the program. Intervening variables, including influences of the family and peers, having a job and access to money, were also found to affect the financial outcomes. (Author abstract)Bolanos, A.B. (2012). Key determinants in building financial capability among middle schoolers with a school-based financial literacy education program. Retrieved from http://academicarchive.snhu.eduDoctor of Philosophy (Ph.D.)School of Busines

High resolution HLA-A, -B, -C and -DRB1 allele and haplotype frequencies in the Costa Rica Central Valley population

The Costa Rica Central Valley population (CCVP) is the major population in this country, accounting for over 60% of the Costa Rican inhabitants concentrated since colonial times in a 2,500 km2 intermontane region. Interesting historic, demographic and genetic characteristics of this hybrid population have attracted researchers interested in testing genetic associations for various diseases. However, no study describing Human Leukocyte Antigen (HLA) frequencies by molecular methods had been performed. We have recently described low resolution HLA allele group and haplotype frequencies in a sample of this population. In this report, we extend our study to high resolution by sequence-based typing of exons 2, 3 and 4 for class I, and exon 2 for HLA-DRB1. DNA was extracted from blood or saliva samples from a cohort of 205 non-related healthy donors recruited as part of the University of Costa Rica’s Centre for Research in Hematology and Related Disorders (CIHATA) DNA bank. All participants were born in the CCVP and gave informed consent. A total of 37 HLA-A, 61 HLA-B, 24 HLA-C and 38 HLA-DRB1 alleles were seen in this sample. The five most frequent alleles for these genes are HLA-A*02:01:01, HLA-A*24:02:01, HLA-A*03:01:01, HLA-A*01:01:01, HLA-A*68:01:02, HLA-B*07:02:01, HLA-B*40:02:01, HLA-B*35:01:01, HLA-B*44:02:01, HLA-B*14:02:01, HLA-C*04:01:01, HLA-C*07:02:01, HLA-C*03:05, HLA-C*06:02:01, HLA-C*07:01:01, HLA-DRB1*13:01:01G, HLA-DRB1*04:07:01G, HLA-DRB1*15:01:01G, HLA-DRB1*03:01:01G, and HLA-DRB1*07:01:01G. Preliminary haplotype estimation results show, as a proxy for admixture proportions, that 68% of the extended haplotypes are Caucasian, while 23% are Amerindian in origin and 9% are clearly Sub-Saharan African. Principal coordinates analysis based on HLA-A and –B allele group frequencies reveals that this population clusters among other admixed groups with strong Caucasian component that lie closely to Iberian populations

The Right to Code and Share Arms

Glycerol is, to date, the most widely used cryoprotectant to freeze stallion spermatozoa at concentrations between 2% and 5%. Cryoprotectant toxicity has been claimed to be the single most limiting factor for the success of cryopreservation. In order to evaluate the toxic effects of the concentrations of glycerol used in practice, stallion spermatozoa were incubated in Biggers Whitten and Whittingham (BWW) media supplemented with 0%, 0.5%, 1.5%, 2.5%, 3.5%, and 5% glycerol. In two additional experiments, a hyposmotic (75 mOsm/kg) and a hyperosmotic (900 mOsm/kg) control media were included. Sperm parameters evaluated included cell volume, membrane integrity, lipid peroxidation, caspase 3, 7, and 8 activation, mitochondrial membrane potential, and integrity of the cytoskeleton. Glycerol exerted toxicity at concentrations 3.5% and the maximal toxicity was observed at 5%. The actin cytoskeleton was especially sensitive to glycerol presence, inducing rapid F actin depolymerization at concentrations over 1.5%. The sperm membrane and the mitochondria were other structures affected. The toxicity of glycerol is apparently related to osmotic and nonosmotic effects. In view of our results the concentration of glycerol in the freezing media for stallion spermatozoa should not surpass 2.5%.Funding Agencies|Ministerio de Ciencia e Innovacion-FEDER Madrid, Spain|AGL 2010 20758 (GAN)|Inia|RZ2008-00018-00-00|Junta de Extremadura FEDER GR|10010

Testing matter effects in propagation of atmospheric and long-baseline neutrinos

We quantify our current knowledge of the size and flavor structure of the matter effects in the evolution of atmospheric and long-baseline neutrinos based solely on the analysis of the corresponding neutrino data. To this aim we generalize the matter potential of the Standard Model by rescaling its strength, rotating it away from the e-e sector, and rephasing it with respect to the vacuum term. This phenomenological parametrization can be easily translated in terms of non-standard neutrino interactions in matter. We show that in the most general case, the strength of the potential cannot be determined solely by atmospheric and long-baseline data. However its flavor composition is very much constrained and the present determination of the neutrino masses and mixing is robust under its presence. We also present an update of the constraints arising from this analysis in the particular case in which no potential is present in the e-mu and e-tau sectors. Finally we quantify to what degree in this scenario it is possible to alleviate the tension between the oscillation results for neutrinos and antineutrinos in the MINOS experiment and show the relevance of the high energy part of the spectrum measured at MINOS.Comment: PDFLaTeX file using JHEP3 class, 25 pages, 7 figures included. Accepted for publication in JHE

Automated Analysis of Cryptococcal Macrophage Parasitism Using GFP-Tagged Cryptococci

The human fungal pathogens Cryptococcus neoformans and C. gattii cause life-threatening infections of the central nervous system. One of the major characteristics of cryptococcal disease is the ability of the pathogen to parasitise upon phagocytic immune effector cells, a phenomenon that correlates strongly with virulence in rodent models of infection. Despite the importance of phagocyte/Cryptococcus interactions to disease progression, current methods for assaying virulence in the acrophage system are both time consuming and low throughput. Here, we introduce the first stable and fully characterised GFP–expressing derivatives of two widely used cryptococcal strains: C. neoformans serotype A type strain H99 and C. gattii serotype B type strain R265. Both strains show unaltered responses to environmental and host stress conditions and no deficiency in virulence in the macrophage model system. In addition, we report the development of a method to effectively and rapidly investigate macrophage parasitism by flow cytometry, a technique that preserves the accuracy of current approaches but offers a four-fold improvement in speed

Bacterial canker caused by Clavibacter michiganensis subsp. michiganensis in naranjilla in Ecuador

Bacterial canker of naranjilla or lulo (Solanum quitoense and Solanum pectinatum) is a new disease that could completely destroy naranjilla plants. The objectives of this study were to identify and characterize bacteria associated with canker wilt of naranjilla, and to determine the importance of wounds in the dissemination and transmission of bacterial canker.Symptoms of this disorder consist of dieback and leaves showing incurvature which was diagnostic to confirm bacterial wilt. Collapse of leaf panel on Nicotiana tabacum confirmed that the bacterium is phytopathogenic. This bacterium showed positive serological tests for Clavibacter michiganensis subsp. michiganensis, positive Gram reaction, growth on NCP 88, (ELISA+ GRAM+ NCP 88 +) as well as re-isolation through Koch postulates in Solanum cheesmanii. Aerial wounds appear to be the most important means for dissemination. More research is needed about the molecular characterization of the bacterium, and potential for the bacterium to be transmitted to other solanaceous crops. Keywords: emerging infectious crop diseases, Solanum quitoense, Solanum pectinatum, Solanum cheesmanii, Solanum hirsutu

Expression Levels of a Kinesin-13 Microtubule Depolymerase Modulates the Effectiveness of Anti-Microtubule Agents

Chemotherapeutic drugs often target the microtubule cytoskeleton as a means to disrupt cancer cell mitosis and proliferation. Anti-microtubule drugs inhibit microtubule dynamics, thereby triggering apoptosis when dividing cells activate the mitotic checkpoint. Microtubule dynamics are regulated by microtubule-associated proteins (MAPs); however, we lack a comprehensive understanding about how anti-microtubule agents functionally interact with MAPs. In this report, we test the hypothesis that the cellular levels of microtubule depolymerases, in this case kinesin-13 s, modulate the effectiveness of the microtubule disrupting drug colchicine.We used a combination of RNA interference (RNAi), high-throughput microscopy, and time-lapse video microscopy in Drosophila S2 cells to identify a specific MAP, kinesin-like protein 10A (KLP10A), that contributes to the efficacy of the anti-microtubule drug colchicine. KLP10A is an essential microtubule depolymerase throughout the cell cycle. We find that depletion of KLP10A in S2 cells confers resistance to colchicine-induced microtubule depolymerization to a much greater extent than depletion of several other destabilizing MAPs. Using image-based assays, we determined that control cells retained 58% (+/-2%SEM) of microtubule polymer when after treatment with 2 microM colchicine for 1 hour, while cells depleted of KLP10A by RNAi retained 74% (+/-1%SEM). Likewise, overexpression of KLP10A-GFP results in increased susceptibility to microtubule depolymerization by colchicine.Our results demonstrate that the efficacy of microtubule destabilization by a pharmacological agent is dependent upon the cellular expression of a microtubule depolymerase. These findings suggest that expression levels of Kif2A, the human kinesin-13 family member, may be an attractive biomarker to assess the effectiveness of anti-microtubule chemotherapies. Knowledge of how MAP expression levels affect the action of anti-microtubule drugs may prove useful for evaluating possible modes of cancer treatment

Cancro bacteriano asociado a Clavibacter michiganensis subsp. michiganensis en naranjilla en Ecuador

Bacterial canker of naranjilla or lulo (Solanum quitoense and Solanum pectinatum) is a new disease that could completely destroy naranjilla plants. The objectives of this study were to identify and characterize bacteria associated with canker wilt of naranjilla, and to determine the importance of wounds in the dissemination and transmission of bacterial canker.Symptoms of this disorder consist of dieback and leaves showing incurvature which was diagnostic to confirm bacterial wilt. Collapse of leaf panel on Nicotiana tabacum confirmed that the bacterium is phytopathogenic. This bacterium showed positive serological tests for Clavibacter michiganensis subsp. michiganensis, positive Gram reaction, growth on NCP 88, (ELISA+ GRAM+ NCP 88 +) as well as re-isolation through Koch postulates in Solanum cheesmanii. Aerial wounds appear to be the most important means for dissemination. More research is needed about the molecular characterization of the bacterium, and potential for the bacterium to be transmitted to other solanaceous crops. Keywords: emerging infectious crop diseases, Solanum quitoense, Solanum pectinatum, Solanum cheesmanii, Solanum hirsutumLa marchitez bacteriana o cancro bacteriano de la naranjilla o lulo (Solanum quitoense y Solanum pectinatum) es una enfermedad con potencial para destruir completamente el cultivo. Los objetivos de este estudio fueron identificar y caracterizar la bacteria o bacterias asociadas al cancro bacteriano en naranjilla y determinar la importancia de las heridas en su transmisión y diseminación. Los síntomas de esta enfermedad consistieron en muerte descendente, y la curvatura de la nervadura principal que constituye un síntoma diagnóstico para la confirmación de marchitez bacteriana. El colapso del panel intervenal (propio de respuesta de hipersensibilidad) en Nicotiana tabacum permitió la confirmación de que la bacteria aislada era patogénica. Esta cepa bacteriana presentó serología positiva para Clavibacter michiganensis subsp. michiganensis, reacción Gram positiva, crecimiento en medio de cultivo semi-selectivo NCP 88 (ELISA+ GRAM+ NCP 88 +), así como re-aislamiento a partir de tejido de Solanum cheesmanii previamente inoculado para cumplir con los postulados de Koch. Heridas aéreas desarrolladas durante la poda con equipo de poda no desinfectado parece ser la forma principal de diseminación. Estudios adicionales son necesarios dirigidos hacia la caracterización molecular de la bacteria, y el potencial de diseminación de la bacteria hacia otras solanáceas. Palabras clave: enfermedades infecciosas emergentes, Solanum quitoense, Solanum pectinatum, Solanum cheesmanii, Solanum hirsutu