| 20591. |
- Vapalahti, O, et al.
(författare)
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Hantavirus infections in Europe
- 2003
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Ingår i: The Lancet. Infectious diseases. - 1473-3099. ; 3:10, s. 653-661
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Tidskriftsartikel (refereegranskat)
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| 20592. |
- Vapalahti, O, et al.
(författare)
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Hantavirus infections in Europe
- 2003
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Ingår i: LANCET INFECTIOUS DISEASES. - 1473-3099. ; 3:12, s. 753-754
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 20593. |
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| 20594. |
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| 20595. |
- Varendi, Heili
(författare)
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Human newborn behavior during exposure to maternal and other odors
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Olfaction appears to play a pivotal role in immediate postnatal interactions between mammalian mothers and their offspring. The present study examined: (1) whether and how the newborn human infant and its mother communicate by means of olfaction; (2) the role of amniotic fluid (AF) and breast odors in such communication; (3) olfactory learning by neonates. An undisturbed communication may play an important role in the initiation and maintenance of breastfeeding. The newborns of studies I-V were uninfluenced by pharmacological pain relief given to the mother. Newborn babies seek and locate the mother's breast within the first hour after birth and prefer an unwashed breast to the washed alternative, indicating that olfaction is implicated in breast seeking behavior (I). Other senses (e.g. vision, touch, temperature sensitivity) may also help the baby to locate the nipple. To determine more precisely the role of olfaction, a cotton pad bearing the mother's breast odor was placed 17 cm in front of the baby who was laying prone on a warm bed. The breast odor elicited crawling movements towards the cotton pad and stereotyped prefeeding behaviors that are typically observed when babies are placed on their mother's chest. These findings indicate that smell, in the absence of other maternal cues, helps guide the baby to the nipple and evokes the behavioral preludes of breastfeeding (V). Amniotic fluid odor is attractive for mammalian neonates. The current study has shown that newborns prefer to suck from a breast treated with AF rather than a naturally smelling breast during the first postnatal hour, possibly reflecting prenatal learning (II). Within several days after birth, the AF preference was replaced by a preference for the natural breast odor, suggesting postnatal olfactory learning (III). Movement of the hand to the mouth and finger sucking are components of the prefeeding behavior displayed immediately after birth. This behavior is disturbed when AF was washed off the baby before it was given to the mother (II). Washing may therefore disrupt prefeeding behavior and proper attachment to the nipple, and related studies have shown that problems with nipple attachment are associated with early breastfeeding failure. Odors can influence behavior during stress. Newborns who were separated from their mother during the first postnatal hours were exposed to either AF odor or maternal breast odor presented on cotton pads. AF soothed newborns, whereas breast odor elicited increased crying relative to control trials (IV). The calming effect of AF might reflect prenatal exposure to that scent. Maternal breast odor may have signalled the presence of food, and the babies became frustrated/agitated when they could not reach the source. Immediate postnatal olfactory learning is shown in several mammals. The capability for early postnatal olfactory learning was studied in Caesarean section delivered babies, who during the first postnatal hour, were exposed for 30 min to an artificial odor (cherry or passion fruit) (VI). Caesarean section delivered babies demonstrated such olfactory learning at testing about three days later, but only if the mothers had experienced uterine contractions before the operation. The norepinephrine levels in the umbilical artery correlated positively to learning. This learning may depend upon locus coeruleus activation and/or the catecholamine surge, and is further evidence that uterine contractions contribute to neonatal adaptation. In summary, the newborn and its mother communicate by means of olfaction. Several common hospital care routines such as washing the baby immediately after birth and the mother's breasts before feeding interfere with this communication and should be avoided until we know more about its clinical significance.
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| 20596. |
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| 20597. |
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| 20598. |
- Vargas, L, et al.
(författare)
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Functional interaction of caveolin-1 with Bruton's tyrosine kinase and Bmx
- 2002
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 277:11, s. 9351-9357
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Tidskriftsartikel (refereegranskat)abstract
- Bruton's tyrosine kinase (Btk), a member of the Tec family of protein-tyrosine kinases, has been shown to be crucial for B cell development, differentiation, and signaling. Mutations in the Btk gene lead to X-linked agammaglobulinemia in humans and X-linked immunodeficiency in mice. Using a co-transfection approach, we present evidence here that Btk interacts physically with caveolin-1, a 22-kDa integral membrane protein, which is the principal structural and regulatory component of caveolae membranes. In addition, we found that native Bmx, another member of the Tec family kinases, is associated with endogenous caveolin-1 in primary human umbilical vein endothelial cells. Second, in transient transfection assays, expression of caveolin-1 leads to a substantial reduction in the in vivo tyrosine phosphorylation of both Btk and its constitutively active form, E41K. Furthermore, a caveolin-1 scaffolding peptide (amino acids 82-101) functionally suppressed the autokinase activity of purified recombinant Btk protein. Third, we demonstrate that mouse splenic B-lymphocytes express substantial amounts of caveolin-1. Interestingly, caveolin-1 was found to be constitutively phosphorylated on tyrosine 14 in these cells. The expression of caveolin-1 in B-lymphocytes and its interaction with Btk may have implications not only for B cell activation and signaling, but also for antigen presentation.
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| 20599. |
- Vargas-Vallejo, Leonardo
(författare)
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Subcellular localization and signalling of Brutons tyrosine kinase (Btk)
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Brutons tyrosine kinase (Btk) is a non-receptor tyrosine kinase related to the Src family of kinases. Mutations in various parts of the gene have been shown to cause X-linked agammaglobulinemia (XLA), a primary immunodeficiency in humans, characterized by a defect in B-cell development. XLA patients lack B-cells and consequentially have very low levels of immunoglobulins in their serum. Thus, these patients suffer from an increased susceptibility mainly to extracellular bacterial infections. The molecular mechanism(s) underlying Btk localization, activation and signaling are not fully understood. We analyzed the subcellular localization of Btk employing a recombinant chimeric Btk fused with the Green Fluorescent Protein (GFP) with subsequent analysis of images using digital confocal microscopy. Different biochemical protein analyses were also performed. During this study we have found that Btk can translocate to the plasma membrane of living cells and play an important role as a potent inducer of cytoskeletal reorganization resulting in membrane ruffle formation. Moreover, we found that Btk can translocate to the nucleus and that Btk utilizes functional CRM-1 dependent nuclear export signal(s) to shuffle between the nucleus and the cytoplasm. We also found that Tec family kinases bind to caveolin-1, a major structural component of caveolae (rafts or microdomains) located in the plasma membrane. Finally, we demonstrate that Cbl acts as an E3-ubiquitin ligase for Btk and that ubiquitinated Btk is targeted for proteasomal degradation when Btk is expressed at high levels. Furthermore, upregulation of the small-ubiquitin-related-modifier (SUMO-1) downregulates Btk. In conclusion, the subcellular localization of Btk has implications regarding cytoskeletal regulation and /or potential targets inside the nucleus, which may be of relevance for B-cell development and differentiation. Also, Cbl-dependent ubiquitination as well as sumoylation are likely to provide a deeper insight into the negative regulation of Btk- mediated cell signaling.
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| 20600. |
- Varmeh-Ziaie, Shohreh
(författare)
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Cloning and characterization of a p-53-inducible gene, WIG-1
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Elucidating the mechanisms by which p53 inhibits tumor growth is a central issue in cancer research, as the TP53 gene is mutated in over half of all human cancers. Lack of functional p53 also contributes to the resistance of many tumor types to chemotherapy and radiotherapy. p53 is a transcription factor, which regulates the expression of a large number of genes. In fact, most of the knowledge about the molecular mechanisms by which p53 exerts its biological functions has been acquired by the identification and characterization of genes whose expression is regulated by p53. This thesis reports on the identification and characterization of a novel p53-inducible gene, designated WIG-1 (Wild type p53 Induced Gene 1). The mouse homologue was first identified by an improved differential display technique. A 7661 bp wig-1 transcript was cloned from the p53negative mouse T lymphoma cell line (J3D), transfected with a temperature-sensitive mouse mutant p53 (Val-135), using the 5 Marathon cDNA amplification technique. Two mouse wig-1 transcripts of 7.6 kb and 2.2 kb were detected in Northern analysis. The 2.2 kb mouse wig-1 transcript was suggested to arise due to alternative polyadenylation and encodes the same zinc finger protein as the 7.6 kb transcript. Mouse wig-1 induction in response to DNA damage was shown to be p53 dependent. Induction of mouse wig-1 was demonstrated to occur in vivo, in a tissue-specific manner by Northern analysis. The coding region of human WIG-1 was cloned from a brain cDNA library. The human and mouse WIG-1 coding sequences are 84% identical at the nucleotide level and 86.9% identical at the amino acid level, with the three conserved zinc finger motifs. Two human WIG-1 transcripts of 8 kb and 6 kb were detected by Northern analysis. Their induction was demonstrated to occur in human cell lines containing wild type p53 but not in cell lines with mutant p53. A p53-specific binding site with perfect match to the p53 consensus-binding site was found in intron 1 of human WIG-1. In vitro binding of wild type p53 to this site was shown by electrophoretic mobility gel shift assay. Tissue- and species-specific basal expression of both human and mouse WIG-1 were demonstrated by Northern analysis. The abundance of both human and mouse WIG-1 mRNAs and the ratio between the transcripts were shown to vary among different tissues. Human and mouse WIG-1 were mapped to 3q26.3 and mouse chromosome 3B, respectively. Human WIG-1 was demonstrated to be amplified with increased expression in primary squamous cell carcinomas of the lung, using Southern blot and RT-PCR analysis. Polyclonal antibodies against the mouse wig-1 were raised and purified. Further investigation into the function of WIG-1 should contribute to a better understanding of the p53-regulated pathways. This in turn will provide further information for logical, interventional therapeutic strategies against p53-deficient tumors.
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