Gene Expression in Biopsies of Acute Rejection and Interstitial Fibrosis/Tubular Atrophy Reveals Highly Shared Mechanisms That Correlate With Worse Long‐Term Outcomes

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/122411/1/ajt13728.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122411/2/ajt13728-sup-0005-AppendixS5.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122411/3/ajt13728-sup-0003-AppendixS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122411/4/ajt13728_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/122411/5/ajt13728-sup-0004-AppendixS4.pd

An association of candidate gene haplotypes and bleeding severity in von Willebrand disease type 2A, 2B, and 2M pedigrees

We analyzed the association of bleeding severity with candidate gene haplotypes within pedigrees of 11 index cases of von Willebrand disease (VWD) type 2 (two type 2A, three type 2B and six type 2M), using the QTL Association model (MENDEL 5.5). In addition to the 11 index cases, these pedigrees included 47 affected and 49 unaffected relatives, as defined by VWF mutations and/or phenotype. A bleeding severity score was derived from a detailed history and adjusted for age. Donors were genotyped using a primer extension method, and eight candidate genes were selected for analysis. VWF antigen (or ristocetin cofactor activity) levels had the strongest influence on bleeding severity score. After Bonferroni correction for multiple testing, only ITGA2 promoter haplotype -52T was associated with an increased bleeding severity score (P < 0.01). This association remained statistically significant when the three type 2B pedigrees were excluded (P= 0.012) or when gender-specific bleeding categories were excluded (P < 0.01). The major haplotypes of seven other candidate genes, GP1BA, ITGA2B, ITGB3, GP6, VWF, FGB, and IL6, were not associated with bleeding severity. These results establish that genetic differences in the expression of the integrin subunit alpha(2) can influence the bleeding phenotype of VWD type 2 and complement our previous findings in VWD type 1. Genetically controlled attenuation of platelet collagen receptor expression can influence risk for morbidity in clinical settings where hemostasis is compromised

Desinfestação e germinação in vitro de sementes de mogno (Swietenia macrophylla King) In vitro sterilization and germination of mahogany seeds (Swietenia macrophylla King)

O presente trabalho teve como objetivos desenvolver técnicas de regeneração in vitro a partir de segmentos de epicótilo, epicótilo invertido e explantes foliares provenientes de plântulas de mogno (Swietenia macrophylla) germinadas em meio de cultura; e determinar a melhor concentração e tempo de exposição das sementes ao agente desinfestante, bem como a melhor posição de semeadura para germinação. As sementes foram desinfestadas, após a retirada do tegumento, em soluções com hipoclorito de sódio nas concentrações de 0; 2,5; e 5,0% (v/v), mantidas embebidas por 10, 20, 30 e 40 minutos e colocadas no meio em duas posições, sendo a posição 1 com a concavidade da parte achatada voltada para cima e na posição 2, com a concavidade da parte achatada voltada para baixo. Após a semeadura, foram mantidas em sala de crescimento com temperatura de &plusmn;26 &plusmn; 2 º C e escuro contínuo. O delineamento utilizado foi o inteiramente casualizado, em esquema fatorial 3 x 4 x 2 (níveis de hipoclorito x tempos de embebição x posição de semeadura), totalizando 24 tratamentos com três repetições. As avaliações de germinação e contaminação por microrganismos ocorreram aos 12, 18, 24 e 30 dias. O melhor tratamento foi a desinfestação das sementes embebidas em 2,5 e 5% de hipoclorito de sódio por 30 e 20 minutos, respectivamente, as quais foram colocadas na posição 2, pois apresentaram a maior germinação (48%) e baixa contaminação (15 e 10%, respectivamente). Quanto à posição, houve diferença significativa aos 24 e 30 dias após a semeadura, com as maiores médias nas sementes colocadas na posição 2.<br>The objective of this work was to develop techniques of in vitro regeneration for mahogany (Swietenia macrophylla), using epicotyl segments, inverted epicotyls and leaf explants from mahogany plantlets germinated in culture medium. Also, the best concentration and time and sterilizing agent for seed sterilization were determined, as well as the best seed sowing position for germination. After tegument removal, seeds were sterilized in sodium hipochlorite solution at 0; 2,5 and 5,0% (v/v) concentrations, kept soaking for 10, 20, 30 and 40 minutes and inoculated in the culture medium in two positions: a) position 1 - with the concavity of the flat part turned upward, and b) position 2 - with the concavity of the flat part turned down. After sowing, seeds were kept in growth room with controlled temperature (&plusmn;26 &plusmn; 2ºC) and continuous dark. An entirely random factorial design, with 3 x 4 x 2 (sodium hipochlorite levels x soaking times x seed position), totaling 24 treatments with 3 repetitions was used. The germination stage and microorganism contamination were evaluated at 12, 18, 24 and 30 days after germination. The best treatments were seed sterilization in 2,5 and 5% sodium hipochlorite for 30 and 20 minutes, respectively, and both inoculated in position 2. These treatment also presented the highest germination rate (48%) and the lowest rates of microorganism contamination (15 e 10% respectively). As for position, a significant difference was detected for 24 and 30 days after sowing, with the largest means for seeds inoculated in position 2