Adenovirus-mediated correction of the genetic defect in hepatocytes from patients with familial hypercholesterolemia

Familial hypercholesterolemia (FH) is an inherited deficiency of LDL receptors that has been an important model for liver-directed gene therapy. We are developing approaches for treating FH that are based on direct delivery of recombinant LDL receptor genes to liver in vivo. As a first step towards this goal, replication-defective recombinant adenoviruses were constructed which contained either the lacZ gene or the human LDL receptor cDNA expressed from a β-actin promoter. Primary cultures of hepatocytes were established from two patients with homozygous FH and one nonFH patient, and subsequently exposed to recombinant adenoviruses at MOIs ranging from 0.1 to 5. Essentially all of the cells expressed high levels of the transgene without demonstrable expression of an early or late adenoviral gene product; the level of recombinant-derived LDL receptor protein in transduced FH hepatocytes exceeded the endogenous levels by at least 20-fold. These studies support the utility of recombinant adenoviruses for efficient transduction of recombinant LDL receptor genes into human FH hepatocytes without expression of viral proteins.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45545/1/11188_2005_Article_BF01233250.pd

Distribution patterns of tau pathology in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is a 4R-tauopathy predominated by subcortical pathology in neurons, astrocytes, and oligodendroglia associated with various clinical phenotypes. In the present international study, we addressed the question of whether or not sequential distribution patterns can be recognized for PSP pathology. We evaluated heat maps and distribution patterns of neuronal, astroglial, and oligodendroglial tau pathologies and their combinations in different clinical subtypes of PSP in postmortem brains. W

Integrating sequence and array data to create an improved 1000 Genomes Project haplotype reference panel

A major use of the 1000 Genomes Project (1000GP) data is genotype imputation in genome-wide association studies (GWAS). Here we develop a method to estimate haplotypes from low-coverage sequencing data that can take advantage of single-nucleotide polymorphism (SNP) microarray genotypes on the same samples. First the SNP array data are phased to build a backbone (or 'scaffold') of haplotypes across each chromosome. We then phase the sequence data 'onto' this haplotype scaffold. This approach can take advantage of relatedness between sequenced and non-sequenced samples to improve accuracy. We use this method to create a new 1000GP haplotype reference set for use by the human genetic community. Using a set of validation genotypes at SNP and bi-allelic indels we show that these haplotypes have lower genotype discordance and improved imputation performance into downstream GWAS samples, especially at low-frequency variants. © 2014 Macmillan Publishers Limited. All rights reserved

Epidemia de encefalite por arbovírus na região sul do Estado de São Paulo, Brasil, em 1975 e 1976: aspectos da distribuição cronológica e geográfica dos casos Encephalitis outbreak in the southern region of the State of S. Paulo in 1975 and 1976: aspects concerning chronological and geographical distribution of the cases

Foi estudada a evolução de uma epidemia de encefalite por arbovirus do grupo B (flavivirus) em 20 municípios da região sul do Estado de São Paulo, Brasil, durante os anos de 1975 e 1976. Verificou-se que a moléstia se propagou em forma de onda epidêmica na direção leste-oeste e leste-sudoeste. A cadeia de montanhas situada ao norte e noroeste da região parece ter-se constituido em barreira à doença. Foi observada também variação estacional, com maior morbidade nos meses de verão e início do outono.<br>The evolution of an encephalitis outbreak due to group B arbovirus was studied in 20 districts in the southern region of the State of S. Paulo, Brazil, in 1975 and 1976. It was noticed that the disease spread in an epidemic wave in the east west and east southwest directions. The mountains located in the north and north west zones seem to have acted as a barrier to the spread of the arboviruses. A seasonal incidence with most of the cases occurring during late Summer and early Fall was also noticed

Changes in aflatoxin standards: Implications for EU border controls of nut imports

This is a pre-copyedited, author-produced version of an article accepted for publication in Applied Economic Perspectives and Policy following peer review. The version of record Garcia-Alvarez-Coque, J.-M., Taghouti, I. and Martinez-Gomez, V. (2020), Changes in Aflatoxin Standards: Implications for EU Border Controls of Nut Imports. Applied Economic Perspectives and Policy, 42: 524-541. doi:10.1093/aepp/ppy036 is available online at: https://doi.org/10.1093/aepp/ppy036.[EN] Food safety concerns about the risk of aflatoxin (AF) contamination have been growing in many regions, particularly in the European Union (EU). To protect consumers from health risks, the EU has established strict standards for maximum acceptable AF levels in food products; these standards have changed several times. This article examines the Rapid Alert System for Food and Feed (RASFF) database, which contains notifications on border controls on AF levels in tree nuts and peanuts. A count data model was used to analyze the impact of political economy considerations, past alerts, and path-dependence effects on RASFF border controls. Policy changes, including the harmonization and relaxing of the EU¿s AF standards, significantly affected the frequency of border controls, with diverse effects among exporting countries. It is believed that the present study provides some insights to the modeling of food standards for explanation or forecasting purposes.García Alvarez-Coque, JM.; Taghouti, I.; Martinez Gomez, VD. (2020). Changes in aflatoxin standards: Implications for EU border controls of nut imports. Applied Economic Perspectives and Policy. 42(3):524-541. https://doi.org/10.1093/aepp/ppy036S524541423Bagwell, K., & Staiger, R. W. (2001). Domestic Policies, National Sovereignty, and International Economic Institutions. The Quarterly Journal of Economics, 116(2), 519-562. doi:10.1162/00335530151144096Baylis, K., Martens, A., & Nogueira, L. (2009). 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V., Breiman, R., Brune, M.-N., … Wilson, D. (2006). Workgroup Report: Public Health Strategies for Reducing Aflatoxin Exposure in Developing Countries. Environmental Health Perspectives, 114(12), 1898-1903. doi:10.1289/ehp.9302Swinnen, J. F. M. (2010). The Political Economy of Agricultural and Food Policies: Recent Contributions, New Insights, and Areas for Further Research. Applied Economic Perspectives and Policy, 32(1), 33-58. doi:10.1093/aepp/ppp012Swinnen, J. (2016). Economics and politics of food standards, trade, and development#. Agricultural Economics, 47(S1), 7-19. doi:10.1111/agec.12316Swinnen, J. F. M., & Vandemoortele, T. (2011). Trade and the Political Economy of Food Standards. Journal of Agricultural Economics, 62(2), 259-280. doi:10.1111/j.1477-9552.2011.00294.xTirole, J. (1996). A Theory of Collective Reputations (with Applications to the Persistence of Corruption and to Firm Quality). 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