DNA-dependent protein kinase is not required for the p53-dependent response to DNA damage.

Damage to DNA in the cell activates the tumour-suppressor protein p53, and failure of this activation leads to genetic instability and a predisposition to cancer. It is therefore crucial to understand the signal transduction mechanisms that connect DNA damage with p53 activation. The enzyme known as DNA-dependent protein kinase (DNA-PK) has been proposed to be an essential activator of p53, but the evidence for its involvement in this pathway is controversial. We now show that the p53 response is fully functional in primary mouse embryonic fibroblasts lacking DNA-PK: irradiation-induced DNA damage in these defective fibroblasts induces a normal response of p53 accumulation, phosphorylation of a p53 serine residue at position 15, nuclear localization and binding to DNA of p53. The upregulation of p53-target genes and cell-cycle arrest also occur normally. The DNA-PK-deficient cell line SCGR11 contains a homozygous mutation in the DNA-binding domain of p53, which may explain the defective response by p53 reported in this line. Our results indicate that DNA-PK activity is not required for cells to mount a p53-dependent response to DNA damage.     

Epidermal growth factor receptor function is necessary for normal craniofacial development and palate closure.

Craniofacial malformations are among the most frequent congenital birth defects in humans; cleft palate, that is inadequate fusion of the palatal shelves, occurs with an annual incidence of 1 in 700 to 1 in 1,000 live births among individuals of European descent. The secondary palate arises as bilateral outgrowths from the maxillary processes, and its formation depends on the coordinated development of craniofacial structures including the Meckel's cartilage and the mandible. Cleft lip and palate syndromes in humans are associated with polymorphisms in the gene (TGFA) encoding transforming growth factor-alpha (TGF-alpha), an epidermal growth factor receptor (EGFR) ligand made by most epithelia. Here we have characterized craniofacial development in Egfr-deficient (Egfr-/-) mice. Newborn Egfr-/- mice have facial mediolateral defects including narrow, elongated snouts, underdeveloped lower jaw and a high incidence of cleft palate. Palatal shelf explants from Egfr-/- mice fused, but frequently had residual epithelium in the midline. In addition, morphogenesis of Meckel's cartilage was deficient in cultured mandibular processes from Egfr-/- embryos. The secretion of matrix metalloproteinases (MMPs) was diminished in Egfr-/- explants, consistent with the ability of EGF to increase MMP secretion and with the decreased MMP expression caused by inhibition of Egfr signalling in wild-type explants. Accordingly, inactivation of MMPs in wild-type explants phenocopied the defective morphology of Meckel's cartilage seen in Egfr-/- explants. Our results indicate that EGFR signalling is necessary for normal craniofacial development and that its role is mediated in part by its downstream targets, the MMPs, and may explain the genetic correlation of human cleft palate with polymorphisms in TGFA.     

The glycocalyx of the epithelial cells of the colon, observed in normal and ulcerous colitic conditions.

Biopsies of subjects affected by ulcerous colitis were stained with ruthenium Red. Alterations of the cellular coat and glycocalyx of the epithelial cells of the colon were identified.     

Distribution of the blood flow supplied by the vertebral artery in rats: anatomical, functional and pharmacological aspects.

In rats, the vertebral artery make only a minor contribution to the blood perfusion of the ponto-medullary area. This was measured with radioactive microspheres and was confirmed by methylmetacrylate casts and local injection of a centrally acting hypotensive drug.     

A family of mammalian Na+-dependent L-ascorbic acid transporters.

Vitamin C (L-ascorbic acid) is essential for many enzymatic reactions, in which it serves to maintain prosthetic metal ions in their reduced forms (for example, Fe2+, Cu+), and for scavenging free radicals in order to protect tissues from oxidative damage. The facilitative sugar transporters of the GLUT type can transport the oxidized form of the vitamin, dehydroascorbic acid, but these transporters are unlikely to allow significant physiological amounts of vitamin C to be taken up in the presence of normal glucose concentrations, because the vitamin is present in plasma essentially only in its reduced form. Here we describe the isolation of two L-ascorbic acid transporters, SVCT1 and SVCT2, from rat complementary DNA libraries, as the first step in investigating the importance of L-ascorbic acid transport in regulating the supply and metabolism of vitamin C. We find that SVCT1 and SVCT2 each mediate concentrative, high-affinity L-ascorbic acid transport that is stereospecific and is driven by the Na+ electrochemical gradient. Despite their close sequence homology and similar functions, the two isoforms of the transporter are discretely distributed: SVCT1 is mainly confined to epithelial systems (intestine, kidney, liver), whereas SVCT2 serves a host of metabolically active cells and specialized tissues in the brain, eye and other organs.     

一种从航天器VLBI观测记录中获取航天器速度信息的方法

介绍一种对航天器的VLBI原始电压观测记录中提取多普勒频移量的方法，并用于对lunarprospector的较左VLBI观测记录的分析中，同时得到航天器的VLBI和多普勒观测数据，有利于对航天器空间位置和速度信息的同时获取。     

Spin Effects in Collisions of Electrons with Atoms and Molecules

IntroductionThedynamicsofelectron-atomandelectron-moleculecollisionshasbeenthefocusofmuchinterestinthepastbecauseofitsrelevanceingasdischargesandplasmas,includinggaslasers,orastrophysicalproblemsofpracticalinterest.Avarietyofinvestigationshavebeenperformedtostudysuchprocessesinsomedetail.Moresophisticatedexperimentalmethodsincludepolarization-correlationmeasurementstoobtaingeneralizedSTUparameters,spinasymmetrieswithpolarizedtargets(alsosuperelasticscatteringfromlaserexcitedtarget),opticalpar…     

Neuere Anschauungen über die Meteorologie und Klimatologie des Föhns

Summary The results of new researches about the föhn in the Swiss Alps in connection with the theory ofH. von Ficker show that the energy of the cyclonic föhn has two sources: the pressure gradient and the baroclinic field. This is caused by the isobaric differences of temperature between the Alps and the free atmosphere in the lee. The result is a current with a descending component in the lee. At the beginning, the descent of the föhn is due to the outstreaming of the cold air on the ground. In its further development the energy of the föhn increases so much as to sweep the cold air off the valleys.The development of föhn in an anticyclonic system ist also explained. Furthermore the two kinds of föhn are discussed in regard to their climatological influences.

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Physikalisch-Meteorologisches Observatorium Davos.