Roles of mismatch repair proteins in the recognition and processing of DNA interstrand crosslinks in human cells

DNA interstrand crosslinks (ICLs) are among the most toxic type of damage to a cell. Many ICL-inducing agents are widely used as therapeutic agents, e.g. cisplatin, psoralen. A bettor understanding of the cellular mechanism that eliminates ICLs is important for the improvement of human health. However, ICL repair is still poorly understood in mammals. Using a triplex-directed site-specific ICL model, we studied the roles of mismatch repair (MMR) proteins in ICL repair in human cells. We are also interested in using psoralen-conjugated triplex-forming oligonucleotides (TFOs) to direct ICLs to a specific site in targeted DNA and in the mammalian genomes. ^ MSH2 protein is the common subunit of two MMR recognition complexes, and MutSα and MutSβ. We showed that MSH2 deficiency renders human cell hypersensitive to psoralen ICLs. MMR recognition complexes bind specifically to triplex-directed psoralen ICLs in vitro. Together with the fact that psoralen ICL-induced repair synthesis is dramatically decreased in MSH2 deficient cell extracts, we demonstrated that MSH2 function is critical for the recognition and processing of psoralen ICLs in human cells. Interestingly, lack of MSH2 does not reduce the level of psoralen ICL-induced mutagenesis in human cells, suggesting that MSH2 does not contribute to error-generating repair of psoralen ICLs, and therefore, may represent a novel error-free mechanism for repairing ICLs. We also studied the role of MLH1, anther key protein in MMR, in the processing of psoralen ICLs. MLH1-deficient human cells are more resistant to psoralen plus UVA treatment. Importantly, MLH1 function is not required for the mutagenic repair of psoralen ICLs, suggesting that it is not involved in the error-generating repair of this type of DNA damage in human cells. ^ These are the first data indicating mismatch repair proteins may participate in a relatively error-free mechanism for processing psoralen ICL in human cells. Enhancement of MMR protein function relative to nucleotide excision repair proteins may reduce the mutagenesis caused by DNA ICLs in humans. ^ In order to specifically target ICLs to mammalian genes, we identified novel TFO target sequences in mouse and human genomes. Using this information, many critical mammalian genes can now be targeted by TFOs.^

Symposium for dental treatment of medically complex children: Practice based culminating experience a continuing education course

The purpose of this Continuing Education Course is to provide oral health professionals with information to address the unique dental needs of medically complex children. The objective is to train dentists to treat special needs patients so these children have more access to oral healthcare. ^ Under the auspice of Dell Children Hospital of Austin, Lisa Jacob DDS MS is administering this Continuing Education Course for dentists and dental staff from the 46 counties of central Texas served by the hospital.^ Needs assessment was determined through a survey questionnaire to collect data about the number of special needs patients seen by general dentists in Central Texas.^ In recent years, an increasing number of continuing education courses have been developed to help dentists learn techniques for providing dentistry in more understanding ways to patients with special needs. Dentists and dental staff are trained to provide care specifically in dentistry, regardless of who the patient is. This means dentists can perform a clinical examination, carry out procedures to diagnose and treat oral diseases, and provide restorations such as fillings and crowns. ^ Four prominent speakers will provide an instructional tool to address the need for dentists to increase their competence and comfort level in caring for individuals with developmental disabilities. Each speaker will address one of the most frequently encountered cases of medically complex children. The four topics selected by Dr. Lisa Jacob are Cancer, Mental Disability, Downs Syndrome, and Craniofacial Syndromes.^ The public health implications of this continuing education course are presented in providing dental service to this underserved population. When general dentist turn away patients with special needs because of lack of knowledge to treat them, these patients will, more than likely, postpone or abandon needed dental visits because of difficulties reaching pediatric dentists who may not be available in certain areas.^

Verification of the clinical implementation of the respiratory gated beam delivery technique with synchrotron-based proton irradiation

The clinical advantage for protons over conventional high-energy x-rays stems from their unique depth-dose distribution, which delivers essentially no dose beyond the end of range. In order to achieve it, accurate localization of the tumor volume relative to the proton beam is necessary. For cases where the tumor moves with respiration, the resultant dose distribution is sensitive to such motion. One way to reduce uncertainty caused by respiratory motion is to use gated beam delivery. The main goal of this dissertation is to evaluate the respiratory gating technique in both passive scattering and scanning delivery mode. Our hypothesis for the study was that optimization of the parameters of synchrotron operation and respiratory gating can lead to greater efficiency and accuracy of respiratory gating for all modes of synchrotron-based proton treatment delivery. The hypothesis is tested in two specific aims. The specific aim #1 is to assess the efficiency of respiratory-gated proton beam delivery and optimize the synchrotron operations for the gated proton therapy. A simulation study was performed and introduced an efficient synchrotron operation pattern, called variable Tcyc. In addition, the simulation study estimated the efficiency in the respiratory gated scanning beam delivery mode as well. The specific aim #2 is to assess the accuracy of beam delivery in respiratory-gated proton therapy. The simulation study was extended to the passive scattering mode to estimate the quality of pulsed beam delivery to the residual motion for several synchrotron operation patterns with the gating technique. The results showed that variable Tcyc operation can offer good reproducible beam delivery to the residual motion at a certain phase of the motion. For respiratory gated scanning beam delivery, the impact of motion on the dose distributions by scanned beams was investigated by measurement. The results showed the threshold for motion for a variety of scan patterns and the proper number of paintings for normal and respiratory gated beam deliveries. The results of specific aims 1 and 2 provided supporting data for implementation of the respiratory gating beam delivery technique into both passive and scanning modes and the validation of the hypothesis.

Caring Minds

Greetings Pacesetter Grads Feel Boost in Entry to Nursing Workforce UTHealth-UH Dual Bachelors Program for First-Time Students UTHealth School of Nursing – By the Numbers 2012 PARTNERS Spring Luncheon – honored “Generations of Nurses” – guest speaker Naomi Judd UT Health Services Expands Care for Patients When I Grow Up, – A UTHealth Nursing Student’s Story Donors Support Start of New Accelerated Family Nurse Practitioner Program Giuseppe Colasurdo, M.D. – Appointed Sixth President in U THealth’s 40-Year History Dean Starck Named to UT Academy of Health Science Education, Marcus Honored by Regents for Outstanding Teaching Students Select Two for 2012 McGovern Awards Endowed scholarships Former home of School of Nursing for 30 years disappears in dust cloud Ruppert Named 2012 FAAN

An analysis of the revenue policy -making process of the Texas Legislature

The purpose of this dissertation was to develop a conceptual framework which can be used to account for policy decisions made by the House Ways and Means Committee (HW&MC) of the Texas House of Representatives. This analysis will examine the actions of the committee over a ten-year period with the goal of explaining and predicting the success of failure of certain efforts to raise revenue.^ The basis framework for modelling the revenue decision-making process includes three major components--the decision alternatives, the external factors and two competing contingency theories. The decision alternatives encompass the particular options available to increase tax revenue. The options were classified as non-innovative or innovative. The non-innovative options included the sales, franchise, property and severance taxes. The innovative options were principally the personal and corporate income taxes.^ The external factors included political and economic constraints that affected the actions of the HW&MC. Several key political constraints on committee decision-making were addressed--including public attitudes, interest groups, political party strength and tradition and precedents. The economic constraints that affected revenue decisions included court mandates, federal mandates and the fiscal condition of the nation and the state.^ The third component of the revenue decision-making framework included two alternative contingency theories. The first alternative theory postulated that the committee structure, including the individual member roles and the overall committee style, resulted in distinctive revenue decisions. This theory will be favored if evidence points to the committee acting autonomously with less concern for the policies of the Speaker of the House. The Speaker assignment theory, postulated that the assignment of committee members shaped or changed the course of committee decision-making. This theory will be favored if there was evidence that the committee was strictly a vehicle for the Speaker to institute his preferred tax policies.^ The ultimate goal of this analysis is to develop an explanation for legislative decision-making about tax policy. This explanation will be based on the linkages across various tax options, political and economic constraints, member roles and committee style and the patterns of committee assignment. ^

Searching for the ideal DNA recognition code of covalent ligands

The combitiatorial approach restriction endonuclease protection selection and amplification REPSA was successfully used to determine ideal DNA interactions sites of covalent ligands. Unlike most other combinatorial methods, REPSA is based on inhibition of enzymatic cleavage by specific ligand-DNA complexes, which enables identification of binding sites of various ligands. However, the inherent nature of this technique posses a problem during selection of binding sites of covalent ligands. By modifying the technique according to the nature of the ligand, we demonstrate the flexibility of REPSA in identifying the preferred binding sites for monocovalent ligands, topoisomerase I and tallimustine, and the bicovalent ligand topoisomerase II. From among the preferred binding sites, we identified the consensus binding sequence of camptothecin induced topoisomerase I cleavage as ‘aGWT/Gc’, and tallimustine consensus sequences as ‘GTTCTA’ and ‘TTTTTTC’. We have shown for the first time that preferential binding of tallimustine occurs at sequences not previously reported. Furthermore, our data indicate that tallimustine is a novel DNA minor groove, guanine-specific alkylating agent. ^ Additionally, we have demonstrated in vivo that sequence-specific covalent DNA-binding small molecules have the ability to regulate transcription by inhibiting RNA polymerase II. Tallimustine, binding to its preferred sequences located in the 5′ untranslated region were an effective impediment for transcribing polymerase II. The ability of covalent binding small molecules to target predetermined DNA sequences located downstream of the promoter suggests a general approach for regulation of gene expression. ^

Discurso político en el escenario internacional : Estudio de caso sobre el presidente Néstor Kirchner

A partir de considerar que el análisis interdisciplinario y crítico de las relaciones entre las estructuras y las estrategias del discurso, la cognición social, la interacción y las relaciones de la sociedad habilita al análisis del discurso a hacer aportes serios al estudio de estructuras, conflictos y problemas sociales. El objetivo de este trabajo es abordar el discurso que el ex presidente de la Nación, Néstor Kirchner, ha efectuado en distintos escenarios internacionales para determinar, dentro de los límites del corpus seleccionado, la correlación y la congruencia del mismo dentro y fuera de la región. Para ello, intentaremos descomponer su discurso en: los distintos componentes que articulan el enunciado y la enunciación, abordaremos estas a través de las marcas del hablante en el discurso, ubicaremos a los receptores del discurso e intentaremos explicar cómo estos recursos son utilizados argumentativamente hablando.

El discurso narrativizado y las normalizaciones citativas : Dos formas solapadas de caracterizar la palabra ajena

Este trabajo de investigación tiene por objeto demostrar que, dentro de un continuum que existe en la reformulación del discurso ajeno en el propio, donde se pasa de una forma a otra casi sin solución de continuidad, se puede hablar de una gradación entre un polo más objetivo (o con pretensión de mayor objetividad) a un polo más subjetivo, donde la interpretación tendría un papel más significativo. El polo más objetivo lo ubicaríamos en el extremo izquierdo y lo ejemplificaríamos con el discurso directo, mientras que el polo más subjetivo ocuparía el extremo derecho y estaría representado por el discurso narrativizado y las nominalizaciones citativas. En medio de estos dos polos se encontrarían todas las demás formas de discurso referido. En el campo del discurso periodístico, donde la investigación fue realizada, se pudo corroborar que existe, en la mayoría de los casos, una elección por parte del locutor (en este caso el periodista) de utilizar una forma u otra. Podría ser objetivo para posteriores estudios el de determinar el criterio que prevalece en esta elección.

Bicentenario, identidad y cambio lingüístico : El sistema verbal de referencia temporal futura en San Juan, Argentina, durante el siglo XIX

En este trabajo enmarcado en la teoría funcional variacionista que relaciona forma, motivación y cultura, pretendemos mostrar cómo el hablante del siglo XIX en San Juan, Argentina, alterna en sus cartas familiares formas lingüísticas sintéticas y perifrásticas para referenciar el futuro, según sus propósitos comunicativos. El corpus, constituido por cartas escritas entre 1837 y 1889, se inserta en el 'siglo de las independencias políticas y las creaciones de los nuevos estados, en que comienza a gestarse la lucha por la identidad en América Latina' (Majfud, 2002). Consideramos que las construcciones alternantes no equivalen entre sí sintáctica, semántica ni pragmáticamente, siendo favorecidas por ciertos parámetros, de los cuales analizamos aquel por el cual creemos entró la innovación de la perífrasis 'ir a + infinitivo'. Adherimos al hecho de que 'las explicaciones funcionales de los cambios lingüísticos no excluyen, sino que implican, las explicaciones culturales' (Coseriu, 1977). Esta aproximación pragmática al uso lingüístico exige un análisis cualitativo y cuantitativo a la vez. 'Importará no sólo qué estructuras contiene la lengua, sino también, cuándo se recurre a ellas y, sobre todo, cuánto se recurre cuándo a qué estructura' (García, 1995)

Raven's progressive matrices test: scale construction and verification of "Flynn effect"

In this paper, the scales of Raven's Progressive Matrices Test, General Scale and Advanced Scale, Series II, for the student population (third cycle of EGB and Polimodal ) in the city of La Plata are presented. Considerations are made as regards both the increase in scores (Flynn effect) observed in relation to the previous scale (1964) and the different mean scores according to two age groups (13-16 and 17-18 years of age) and education mode. The findings enabled inferences related to the significance of the increase, particularly in the case of the higher scores in the population attending a special kind of educational institution.

El discurso narrativizado y las normalizaciones citativas : Dos formas solapadas de caracterizar la palabra ajena

Este trabajo de investigación tiene por objeto demostrar que, dentro de un continuum que existe en la reformulación del discurso ajeno en el propio, donde se pasa de una forma a otra casi sin solución de continuidad, se puede hablar de una gradación entre un polo más objetivo (o con pretensión de mayor objetividad) a un polo más subjetivo, donde la interpretación tendría un papel más significativo. El polo más objetivo lo ubicaríamos en el extremo izquierdo y lo ejemplificaríamos con el discurso directo, mientras que el polo más subjetivo ocuparía el extremo derecho y estaría representado por el discurso narrativizado y las nominalizaciones citativas. En medio de estos dos polos se encontrarían todas las demás formas de discurso referido. En el campo del discurso periodístico, donde la investigación fue realizada, se pudo corroborar que existe, en la mayoría de los casos, una elección por parte del locutor (en este caso el periodista) de utilizar una forma u otra. Podría ser objetivo para posteriores estudios el de determinar el criterio que prevalece en esta elección.

Bicentenario, identidad y cambio lingüístico : El sistema verbal de referencia temporal futura en San Juan, Argentina, durante el siglo XIX

En este trabajo enmarcado en la teoría funcional variacionista que relaciona forma, motivación y cultura, pretendemos mostrar cómo el hablante del siglo XIX en San Juan, Argentina, alterna en sus cartas familiares formas lingüísticas sintéticas y perifrásticas para referenciar el futuro, según sus propósitos comunicativos. El corpus, constituido por cartas escritas entre 1837 y 1889, se inserta en el 'siglo de las independencias políticas y las creaciones de los nuevos estados, en que comienza a gestarse la lucha por la identidad en América Latina' (Majfud, 2002). Consideramos que las construcciones alternantes no equivalen entre sí sintáctica, semántica ni pragmáticamente, siendo favorecidas por ciertos parámetros, de los cuales analizamos aquel por el cual creemos entró la innovación de la perífrasis 'ir a + infinitivo'. Adherimos al hecho de que 'las explicaciones funcionales de los cambios lingüísticos no excluyen, sino que implican, las explicaciones culturales' (Coseriu, 1977). Esta aproximación pragmática al uso lingüístico exige un análisis cualitativo y cuantitativo a la vez. 'Importará no sólo qué estructuras contiene la lengua, sino también, cuándo se recurre a ellas y, sobre todo, cuánto se recurre cuándo a qué estructura' (García, 1995)

Raven's progressive matrices test: scale construction and verification of "Flynn effect"

In this paper, the scales of Raven's Progressive Matrices Test, General Scale and Advanced Scale, Series II, for the student population (third cycle of EGB and Polimodal ) in the city of La Plata are presented. Considerations are made as regards both the increase in scores (Flynn effect) observed in relation to the previous scale (1964) and the different mean scores according to two age groups (13-16 and 17-18 years of age) and education mode. The findings enabled inferences related to the significance of the increase, particularly in the case of the higher scores in the population attending a special kind of educational institution.

Discurso político en el escenario internacional : Estudio de caso sobre el presidente Néstor Kirchner

A partir de considerar que el análisis interdisciplinario y crítico de las relaciones entre las estructuras y las estrategias del discurso, la cognición social, la interacción y las relaciones de la sociedad habilita al análisis del discurso a hacer aportes serios al estudio de estructuras, conflictos y problemas sociales. El objetivo de este trabajo es abordar el discurso que el ex presidente de la Nación, Néstor Kirchner, ha efectuado en distintos escenarios internacionales para determinar, dentro de los límites del corpus seleccionado, la correlación y la congruencia del mismo dentro y fuera de la región. Para ello, intentaremos descomponer su discurso en: los distintos componentes que articulan el enunciado y la enunciación, abordaremos estas a través de las marcas del hablante en el discurso, ubicaremos a los receptores del discurso e intentaremos explicar cómo estos recursos son utilizados argumentativamente hablando.

Bicentenario, identidad y cambio lingüístico : El sistema verbal de referencia temporal futura en San Juan, Argentina, durante el siglo XIX

En este trabajo enmarcado en la teoría funcional variacionista que relaciona forma, motivación y cultura, pretendemos mostrar cómo el hablante del siglo XIX en San Juan, Argentina, alterna en sus cartas familiares formas lingüísticas sintéticas y perifrásticas para referenciar el futuro, según sus propósitos comunicativos. El corpus, constituido por cartas escritas entre 1837 y 1889, se inserta en el 'siglo de las independencias políticas y las creaciones de los nuevos estados, en que comienza a gestarse la lucha por la identidad en América Latina' (Majfud, 2002). Consideramos que las construcciones alternantes no equivalen entre sí sintáctica, semántica ni pragmáticamente, siendo favorecidas por ciertos parámetros, de los cuales analizamos aquel por el cual creemos entró la innovación de la perífrasis 'ir a + infinitivo'. Adherimos al hecho de que 'las explicaciones funcionales de los cambios lingüísticos no excluyen, sino que implican, las explicaciones culturales' (Coseriu, 1977). Esta aproximación pragmática al uso lingüístico exige un análisis cualitativo y cuantitativo a la vez. 'Importará no sólo qué estructuras contiene la lengua, sino también, cuándo se recurre a ellas y, sobre todo, cuánto se recurre cuándo a qué estructura' (García, 1995)