gaddl53 encodes a CCAAT/enhancer-binding protein (C/EBP)-related protein that lacks a functional DNA-binding domain. Since the gadd153 protein is capable of heterodimerizing with other C/EBPs, gadd153 may function as a negative regulator of these transcription factors. Here we examined the role of glucose in regulating gadd153 expression. We found that glucose deprivation markedly induces gaddl53 mRNA levels in both HeLa and 3T3-L1 cells and that addition of D-(+)-glucose resulted in a rapid decrease ofgaddl53 mRNA. Similar induction and reversal of gadd153 expression were observed at the protein level. Because C/EBPat appears to play an important role in regulating genes involved in adipogenesis and energy metabolism, we examined gaddl53 expression during the differentiation of 3T3-L1 preadipocytes and as a function of glucose utilization in differentiated adipocytes. Using a standard differentiation protocol that consisted of hormonal stimulation for 2 days followed by medium changes every 2 days thereafter, we observed that both C/EBPoa and gaddl53 mRNAs were elevated. However, C/EBPa induction occurred on day 3, while gaddl53 expression was not seen until day 4, when the cells were fully differentiated. Frequent addition of fresh medium to the cells during the differentiation process, as well as supplementation of medium with glucose, reduced gaddl53 expression without preventing C/EBPa expression or interfering with cellular differentiation. Thus, gaddl53 expression is not essential for the process of adipocyte differentiation but is significantly influenced by the availability of glucose to the cell. gaddl53 is a mammalian gene whose expression is induced by a wide variety of stresses, including growth arrest and DNA damage (16,20,21). gaddlS3 encodes a 19-kDa protein related to the CCAAT/enhancer-binding protein (C/ EBP) family of transcription factors (28). The C/EBPs are bZip proteins characterized by a conserved leucine zipper domain, through which various C/EBP monomers dimerize, adjacent to a basic domain involved in DNA sequence recognition and binding. Although the gaddl53 protein forms stable heterodimers with other C/EBP proteins, it lacks a functional DNA-binding domain (28). Thus, the gaddlS3 protein-C/EBP heterodimer is unable to bind known C/EBP-binding sites, suggesting that gaddlS3 may function as a negative regulator of C/EBP transcription factors.It has been hypothesized that C/EBPa is a central regulator of genes encoding proteins involved in energy metabolism (22). This proposal is based on the following observations: levels of C/EBPa expression are high in tissues with high rates of metabolism, such as liver, adipose, and placenta; the developmental pattern of C/EBPot expression in the liver coincides with the onset of gluconeogenic activity; C/EBPa can trans activate the promoters of genes involved in energy metabolism; and livers of cl4CoS/clCS mice show reduced levels of C/EBPa expression. These mutant mice, containing radiation-induced deletions involving the albino locus on chromo...

The levels of microRNAs (miRNAs) are altered under different conditions such as cancer, senescence, and aging. Here, we have identified differentially expressed miRNAs in skeletal muscle from young and old rhesus monkeys using RNA sequencing. In old muscle, several miRNAs were upregulated, including miR-451, miR-144, miR-18a and miR-15a, while a few miRNAs were downregulated, including miR-181a and miR-181b. A number of novel miRNAs were also identified, particularly in old muscle. We also examined the impact of caloric restriction (CR) on miRNA abundance by reverse transcription (RT) followed by real-time, quantitative (q)PCR analysis and found that CR rescued the levels of miR-181b and chr1:205580546, and also dampened the age-induced increase in miR-451 and miR-144 levels. Our results reveal that there are changes in expression of known and novel miRNAs with skeletal muscle aging and that CR may reverse some of these changes to a younger phenotype.

Natural killer (NK) cells play a key role in defense against tumor cells that have the capacity to downregulate human leukocyte antigen (HLA) class I expression. It has been reported that leukemic cells can have downregulated expression of HLA class I molecules. The polymorphic nature of NK cell receptor (NKR) genes generates diverse repertoires in the human population, which display specificity in the innate immune response. In the present study, 11 KIR and two CD94/NKG2 receptors were genotyped by PCR-SSP in 96 leukemic patients and 148 healthy Caucasians. Here, we report a significant increased frequency of the more inhibitory AB killer cell immunoglobulin-like receptor (KIR) phenotype in leukemic patients compared to the controls (31.1% in healthy controls vs 51.0% in leukemic patients, P c ¼ 0.002), which is related to the high prevalence of the inhibitory KIR2DL2 in this population (P c ¼ 0.007). Moreover, two specific KIR phenotypes AB1 and AB9, including all inhibitory KIRs, were significantly associated with leukemic patients. Our study suggests that an important percentage of leukemic patients express a KIR phenotype in favor of escape from NK cell immunity.

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Real-time 3D Echocardiography (RT3DE) has been proven to be an accurate tool for left ventricular (LV) volume assessment. However, identification of the LV endocardium remains a challenging task, mainly because of the low tissue/blood contrast of the images combined with typical artifacts. Several semi and fully automatic algorithms have been proposed for segmenting the endocardium in RT3DE data in order to extract relevant clinical indices, but a systematic and fair comparison between such methods has so far been impossible due to the lack of a publicly available common database. Here, we introduce a standardized evaluation framework to reliably evaluate and compare the performance of the algorithms developed to segment the LV border in RT3DE. A database consisting of 45 multivendor cardiac ultrasound recordings acquired at different centers with corresponding reference measurements from three experts are made available. The algorithms from nine research groups were quantitatively evaluated and compared using the proposed online platform. The results showed that the best methods produce promising results with respect to the experts' measurements for the extraction of clinical indices, and that they offer good segmentation precision in terms of mean distance error in the context of the experts' variability range. The platform remains open for new submissions.