The protein EP300 and its paralog CREBBP (CREB-binding protein) are ubiquitously expressed transcriptional co-activators and histone acetyl transferases. The gene EP300 is essential for normal ...cardiac and neural development, whereas CREBBP is essential for neurulation, hematopoietic differentiation, angiogenesis and skeletal and cardiac development. Mutations in CREBBP cause Rubinstein-Taybi syndrome, which is characterized by mental retardation, skeletal abnormalities and congenital cardiac defects. The CBP/p300-interacting transactivator with ED-rich tail 2 (CITED2) binds EP300 and CREBBP with high affinity and regulates gene transcription. Here we show that Cited2−/− embryos die with cardiac malformations, adrenal agenesis, abnormal cranial ganglia and exencephaly. The cardiac defects include atrial and ventricular septal defects, overriding aorta, double-outlet right ventricle, persistent truncus arteriosus and right-sided aortic arches. We find increased apoptosis in the midbrain region and a marked reduction in ErbB3-expressing neural crest cells in mid-embryogenesis. We show that CITED2 interacts with and co-activates all isoforms of transcription factor AP-2 (TFAP2). Transactivation by TFAP2 isoforms is defective in Cited2−/− embryonic fibroblasts and is rescued by ectopically expressed CITED2. As certain Tfap2 isoforms are essential in neural crest, neural tube and cardiac development, we propose that abnormal embryogenesis in mice lacking Cited2 results, at least in part, from its role as a Tfap2 co-activator.
The effects of respiratory viral infection on the time course of chronic obstructive pulmonary disease (COPD) exacerbation were examined by monitoring changes in systemic inflammatory markers in ...stable COPD and at exacerbation. Eighty-three patients with COPD (mean SD age, 66.6 7.1 yr, FEV(1), 1.06 0.61 L) recorded daily peak expiratory flow rate and any increases in respiratory symptoms. Nasal samples and blood were taken for respiratory virus detection by culture, polymerase chain reaction, and serology, and plasma fibrinogen and serum interleukin-6 (IL-6) were determined at stable baseline and exacerbation. Sixty-four percent of exacerbations were associated with a cold occurring up to 18 d before exacerbation. Seventy-seven viruses (39 58.2% rhinoviruses) were detected in 66 (39.2%) of 168 COPD exacerbations in 53 (64%) patients. Viral exacerbations were associated with frequent exacerbators, colds with increased dyspnea, a higher total symptom count at presentation, a longer median symptom recovery period of 13 d, and a tendency toward higher plasma fibrinogen and serum IL-6 levels. Non-respiratory syncytial virus (RSV) respiratory viruses were detected in 11 (16%), and RSV in 16 (23.5%), of 68 stable COPD patients, with RSV detection associated with higher inflammatory marker levels. Respiratory virus infections are associated with more severe and frequent exacerbations, and may cause chronic infection in COPD. Prevention and early treatment of viral infections may lead to a decreased exacerbation frequency and morbidity associated with COPD.
Apoptosis is a form of regulated cell death (RCD) that involves proteases of the caspase family. Pharmacological and genetic strategies that experimentally inhibit or delay apoptosis in mammalian ...systems have elucidated the key contribution of this process not only to (post-)embryonic development and adult tissue homeostasis, but also to the etiology of multiple human disorders. Consistent with this notion, while defects in the molecular machinery for apoptotic cell death impair organismal development and promote oncogenesis, the unwarranted activation of apoptosis promotes cell loss and tissue damage in the context of various neurological, cardiovascular, renal, hepatic, infectious, neoplastic and inflammatory conditions. Here, the Nomenclature Committee on Cell Death (NCCD) gathered to critically summarize an abundant pre-clinical literature mechanistically linking the core apoptotic apparatus to organismal homeostasis in the context of disease.
Melon (Cucumis melo L.) is highly nutritious vegetable species and an important source of β-carotene (Vitamin A), which is an important nutrient in the human diet. A previously developed set of 81 ...recombinant inbred lines (RIL) derived from Group Cantalupensis US Western Shipper market type germplasm was examined in two locations Wisconsin (WI) and California (CA), USA over 2 years to identify quantitative trait loci (QTL) associated with quantity of beta-carotene (QβC) in mature fruit. A moderately saturated 256-point RIL-based map 104 SSR, 7 CAPS, 4 SNP in putative carotenoid candidate genes, 140 dominant markers and one morphological trait (a) spanning 12 linkage groups (LG) was used for QβC-QTL analysis. Eight QTL were detected in this evaluation that were distributed across four LG that explained a significant portion of the associated phenotypic variation for QβC (R ² = 8 to 31.0%). Broad sense heritabilities for QβC obtained from RIL grown in WI. and CA were 0.56 and 0.68, respectively, and 0.62 over combined locations. The consistence of QβC in high/low RIL within location across years was confirmed in experiments conducted over 2 years. QTL map positions were not uniformly associated with putative carotenoid genes, although one QTL (β-car6.1) interval was located 10 cM from a β-carotene hydroxylase gene. These results suggest that accumulation of β-carotene in melon is under complex genetic control. This study provides the initial step for defining the genetic control of QβC in melon leading to the development of varieties with enhanced β-carotene content.
We simulate the growth of galaxies and their central supermassive black holes by implementing a suite of semi-analytic models on the output of the Millennium Run, a very large simulation of the ...concordance Λ cold dark matter cosmogony. Our procedures follow the detailed assembly history of each object and are able to track the evolution of all galaxies more massive than the Small Magellanic Cloud throughout a volume comparable to that of large modern redshift surveys. In this first paper we supplement previous treatments of the growth and activity of central black holes with a new model for ‘radio’ feedback from those active galactic nuclei that lie at the centre of a quasi-static X-ray-emitting atmosphere in a galaxy group or cluster. We show that for energetically and observationally plausible parameters such a model can simultaneously explain: (i) the low observed mass drop-out rate in cooling flows; (ii) the exponential cut-off at the bright end of the galaxy luminosity function; and (iii) the fact that the most massive galaxies tend to be bulge-dominated systems in clusters and to contain systematically older stars than lower mass galaxies. This success occurs because static hot atmospheres form only in the most massive structures, and radio feedback (in contrast, for example, to supernova or starburst feedback) can suppress further cooling and star formation without itself requiring star formation. We discuss possible physical models that might explain the accretion rate scalings required for our phenomenological ‘radio mode’ model to be successful.
A range of methods, mainly X-Ray Diffraction (XRD) and Differential Scanning Calorimetry (DSC), have been used to characterise the polymorphism of fats in food products. As sugars present in ...chocolate have a significant XRD pattern, partially overlapping with the signal of cocoa butter, XRD cannot be applied directly to chocolate. In this paper, the XRD signal of a molten sample, similar to the one for pure sucrose, was subtracted from the signal of a solid sample of chocolate to remove the impact of the crystallised sugar. The XRD patterns obtained were compared with the pattern of cocoa butter cooled under the same conditions. Strong peaks were observed at similar inter lamellar d spacings showing that the polymorphic state of cocoa butter in processed chocolate could be obtained using this method. Numerical integration of the peaks also allowed quantification of the degree of crystallinity present in the system during a typical process. The accuracy of the method developed was found to be dependent on the (cocoa butter)/(sugar) ratio in the chocolate used.
The Navy Prototype Optical Interferometer Armstrong, J. T; Mozurkewich, D; Rickard, L. J ...
The Astrophysical journal,
03/1998, Letnik:
496, Številka:
1
Journal Article
Expression of MUC1 in endometrial epithelium has been suggested to create a barrier to embryo attachment that must be lifted
at the time of implantation. In this study, we investigated the hormonal ...regulation of human endometrial MUC1 in hormone replacement
therapy cycles and in the human blastocyst. We also analyzed the embryonic regulation of MUC1 in human endometrial epithelial
cells (EECs) during the apposition and adhesion phases of human implantation using two different in vitro models. Our results
indicate that endometrial MUC1 mRNA and immunoreactive protein increase in receptive endometrium compared to nonreceptive
endometrium. Human blastocysts express MUC1, as demonstrated by reverse transcription-polymerase chain reaction and immunocytochemistry,
localized at the trophectoderm. In vitro, MUC1 was present at the surface of primary cultures of human EEC, and presence of
a human blastocyst (i.e., apposition phase) increases EEC MUC1 protein and mRNA compared to control EEC lacking embryos. Interestingly,
when human blastocysts were allowed to attach to the EEC monolayer (i.e., adhesion phase), MUC1 was locally removed in a paracrine
fashion on EEC at the implantation site. These results demonstrate a coordinated hormonal and embryonic regulation of EEC
MUC1. Progesterone combined with estradiol priming induces an up-regulation of MUC1 at the receptive endometrium. During the
apposition phase, presence of a human embryo increases EEC MUC1. However, at the adhesion phase, the embryo induces a paracrine
cleavage of EEC MUC1 at the implantation site. These findings strongly suggest that MUC1 may act as an endometrial antiadhesive
molecule that must be locally removed by the human blastocyst during the adhesion phase.
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