Iowa Technology Governance Board Annual Report, January 9, 2006

This is the annual report of the Technology Governance Board that is established in Iowa Code Section 8A.204. This annual report was produced in compliance with Iowa Code §8A.204(3a) and was submitted to the Governor, the Department of Management, and the General Assembly on January 9, 2006.

Intracisternal delivery of NFκB-inducible scAAV2/9 reveals locoregional neuroinflammation induced by systemic kainic acid treatment.

We have previously demonstrated disease-dependent gene delivery in the brain using an AAV vector responding to NFκB activation as a probe for inflammatory responses. This vector, injected focally in the parenchyma prior to a systemic kainic acid (KA) injection mediated inducible transgene expression in the hippocampus but not in the cerebellum, regions, respectively, known to be affected or not by the pathology. However, such a focal approach relies on previous knowledge of the model parameters and does not allow to predict the whole brain response to the disease. Global brain gene delivery would allow to predict the regional distribution of the pathology as well as to deliver therapeutic factors in all affected brain regions. We show that self-complementary AAV2/9 (scAAV2/9) delivery in the adult rat cisterna magna allows a widespread but not homogenous transduction of the brain. Indeed, superficial regions, i.e., cortex, hippocampus, and cerebellum were more efficiently transduced than deeper regions, such as striatum, and substantia nigra. These data suggest that viral particles penetration from the cerebrospinal fluid (CSF) into the brain is a limiting factor. Interestingly, AAV2/9-2YF a rationally designed capsid mutant (affecting surface tyrosines) increased gene transfer efficiency approximately fivefold. Neurons, astrocytes, and oligodendrocytes, but not microglia, were transduced in varying proportions depending on the brain region and the type of capsid. Finally, after a single intracisternal injection of scAAV2/9-2YF using the NFκB-inducible promoter, KA treatment induced transgene expression in the hippocampus and cortex but not in the cerebellum, corresponding to the expression of the CD11b marker of microglial activation. These data support the use of disease-inducible vectors administered in the cisterna magna as a tool to characterize the brain pathology in systemic drug-induced or transgenic disease models. However, further improvements are required to enhance viral particles penetration into the brain.

Iowa Lottery Action, February 6-9, 2006, Vol. 13, no. 3

Iowa Lottery newsletter for retailers

The role of the T-cell receptor (TCR) in alpha beta/gamma delta lineage commitment: clues from intracellular TCR staining.

T cells belong to two mutually exclusive lineages expressing either alpha beta or gamma delta T-cell receptors (TCR). Although alpha beta and gamma delta cells are known to share a common precursor the role of TCR rearrangement and specificity in the lineage commitment process is controversial. Instructive lineage commitment models endow the alpha beta or gamma delta TCR with a deterministic role in lineage choice, whereas separate lineage models invoke TCR-independent lineage commitment followed by TCR-dependent selection and maturation of alpha beta and gamma delta cells. Here we review the published data pertaining to the role of the TCR in alpha beta/gamma delta lineage commitment and provide some additional information obtained from recent intracellular TCR staining studies. We conclude that a variant of the separate lineage model is best able to accommodate all of the available experimental results.

A limited role for beta-selection during gamma delta T cell development.

T cells belong to two distinct lineages expressing either alpha beta or gamma delta TCR. During alpha beta T cell development, it is clearly established that productive rearrangement at the TCR beta locus in immature precursor cells leads to the expression of a pre-TCR complex. Signaling through the pre-TCR results in the selective proliferation and maturation of TCR beta+ cells, a process that is known as beta-selection. However, the potential role of beta-selection during gamma delta T cell development is controversial. Whereas PCR-RFLP and sequencing techniques have provided evidence for a bias toward in-frame VDJ beta rearrangements in gamma delta cells (consistent with beta-selection), gamma delta cells apparently develop normally in mice that are unable to assemble a pre-TCR complex due to a deficiency in TCR beta or pT alpha genes. In this report, we have directly addressed the physiologic significance of beta-selection during gamma delta cell development in normal mice by quantitating intracellular TCR beta protein in gamma delta cells and correlating its presence with cell cycle status. Our results indicate that beta-selection plays a significant (although limited) role in gamma delta cell development by selectively amplifying a minor subset of gamma delta precursor cells with productively rearranged TCR beta genes.

Déclaration du Roy, qui permet à la Compagnie des Indes Orientales de vendre les étoffes des Indes qu'elle a reçû par ses vaisseaux, tant celles de soye pure que celles de soye meslée d'or & d'argent ... Donnée à Versailles le 9. May 1702

[Acte royal. 1702-05-09. Versailles]

6,5 · 10-9

Segons l’Institut Nacional d’Estadística, cada espanyol es gasta una mitjana de208 euros a l’any en loteries. L’objectiu principal és guanyar el primer premi, peròsaben realment quina probabilitat tenen d’aconseguir-ho?L’objectiu principal del treball és estudiar el funcionament, les probabilitats i lespreferències dels individus pel que fa a les loteries. Donat que és un sector molt ampli icomplex hem decidit centrar-nos en aquelles que tenen una major acceptació.Les loteries no només son un tema d’interès general sinó que ens han permès aprofundiren els coneixements estadístics adquirits a les assignatures de Probabilitat, Estadística iDecisió i Competència Estratègica.L’anàlisi del treball es centrarà en el càlcul de les probabilitats. Els ingressos de l’Estatprovinents dels impostos sobre la comercialització i sobre els beneficis generats per laloteria també es veuran reflectits en l’estudi. A més analitzarem les preferències de lapoblació a l’hora de jugar a la loteria mitjançant la realització d’enquestes. Després decomparar els resultats obtinguts en les enquestes amb les probabilitats calculadesinicialment, realitzarem una simulació que ens permetrà aprofundir més en el tema.El càlcul de les probabilitats de guanyar en cada joc no estan reflectits en cap documentoficial. Aquest fet resulta paradoxal ja que els càlculs no tenen una gran complicació,aleshores, per què no son públics? Segurament perquè el coneixement d’aquestes dadesfaria que la gent deixes de jugar, amb el que els extensos ingressos procedents de lacomercialització de loteries, disminuiria considerablement.

Iowa Department of Elder Affairs Legislative Update, March 4, 2005, Vol. 1, no. 9

Iowa Department of Elder Affairs provides a brief summation of a Departmental program or other important Departmental information in each Legislative Update. The Legislative Update is produced for informational and educational purposes only.

EPI Update, June 9, 2006

Weekly newsletter for Center For Acute Disease Epidemiology of Iowa Department of Public Health.