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111.
Rats can be classified as either sucralose avoiders (SA) or sucralose preferrers (SP) based on their behavioral responses in 2-bottle preference, 1-bottle intake, and brief-access licking tests. The present study demonstrates that this robust phenotypic variation in the preference for sucralose predicts acceptance of saccharin, an artificial sweetener with a purported concentration-dependent "bitter" side taste and a 0.25 M sucrose solution adulterated with increasing concentrations of quinine hydrochloride (QHCl). Specifically, SA displayed decreased preference for and intakes of saccharin (≥41.5 mM) and sucrose-QHCl (>0.5 mM QHCl) solutions, relative to SP. In a second experiment involving brief-access (30-s) tests, SP and SA did not differ in their unconditioned licking responses across a range of sodium chloride or QHCl solutions (0.03-1 mM). However, the acceptability threshold for sucrose was lower in SA, relative to SP (0.06 and 0.13 M, respectively). Our findings suggest that phenotypic differences in sucralose preference are indicative of a more general difference in the hedonic processing of stimuli containing "bittersweet" or "sweet" taste qualities. 相似文献
112.
P M Colman W R Tulip J N Varghese P A Tulloch A T Baker W G Laver G M Air R G Webster 《Philosophical transactions of the Royal Society of London. Series B, Biological sciences》1989,323(1217):511-518
X-ray diffraction analysis of crystals of a monoclonal Fab fragment NC41 bound to a viral antigen, influenza virus neuraminidase, shows an epitope involving five surface loops of the antigen. In addition it reveals an unusual pairing pattern between the domains of light and heavy chains in the variable module of the antibody. We interpret this result to imply that association with antigen can induce changes in the quaternary structure of the Fab, through a sliding of domains at the variable light/variable heavy chains (VL-VH) interface. In addition, Fab binding has altered the conformation of some of the surface loops of the antigen. The structure of the NC10 Fab-neuraminidase complex has now also been solved. It binds an epitope that overlaps the NC41 epitope. In this structure, there is no electron density for the C-module of the Fab fragment, implying it is disordered in the crystal lattice. The implications of these, and other antibody-antigen structures, for immune recognition are discussed. 相似文献
113.
114.
Tulloch PA Lawrence LJ McKern NM Robinson CP Bentley JD Cosgrove L Ivancic N Lovrecz GO Siddle K Ward CW 《Journal of structural biology》1999,125(1):11-18
The insulin receptor (IR) is a four-chain, transmembrane dimer held together by disulfide bonds. To gain information about the molecular envelope and the organization of its domains, single-molecule images of the IR ectodomain and its complexes with three Fabs have been analyzed by electron microscopy. The data indicate that the IR ectodomain resembles a U-shaped prism of approximate dimensions 90 x 80 x 120 A. The width of the cleft (assumed membrane-distal) between the two side arms is sufficient to accommodate ligand. Fab 83-7, which recognizes the cys-rich region of IR, bound halfway up one end of each side arm in a diametrically opposite manner, indicating a twofold axis of symmetry normal to the membrane surface. Fabs 83-14 and 18-44, which have been mapped respectively to the first fibronectin type III domain (residues 469-592) and residues 765-770 in the insert domain, bound near the base of the prism at opposite corners. These images, together with the data from the recently determined 3D structure of the first three domains of the insulin-like growth factor type I receptor, suggest that the IR dimer is organized into two layers with the L1/cys-rich/L2 domains occupying the upper (membrane distal) region of the U-shaped prism and the fibronectin type III domains and the insert domains located predominantly in the membrane-proximal region. 相似文献
115.
Bartlett EJ Cruz AM Esker J Castaño A Schomacker H Surman SR Hennessey M Boonyaratanakornkit J Pickles RJ Collins PL Murphy BR Schmidt AC 《Journal of virology》2008,82(18):8965-8977
Recombinant human parainfluenza virus type 1 (rHPIV1) was modified to create rHPIV1-P(C-), a virus in which expression of the C proteins (C', C, Y1, and Y2) was silenced without affecting the amino acid sequence of the P protein. Infectious rHPIV1-P(C-) was readily recovered from cDNA, indicating that the four C proteins were not essential for virus replication. Early during infection in vitro, rHPIV1-P(C-) replicated as efficiently as wild-type (wt) HPIV1, but its titer subsequently decreased coincident with the onset of an extensive cytopathic effect not observed with wt rHPIV1. rHPIV1-P(C-) infection, but not wt rHPIV1 infection, induced caspase 3 activation and nuclear fragmentation in LLC-MK2 cells, identifying the HPIV1 C proteins as inhibitors of apoptosis. In contrast to wt rHPIV1, rHPIV1-P(C-) and rHPIV1-C(F170S), a mutant encoding an F170S substitution in C, induced interferon (IFN) and did not inhibit IFN signaling in vitro. However, only rHPIV1-P(C-) induced apoptosis. Thus, the anti-IFN and antiapoptosis activities of HPIV1 were separable: both activities are disabled in rHPIV1-P(C-), whereas only the anti-IFN activity is disabled in rHPIV1-C(F170S). In African green monkeys (AGMs), rHPIV1-P(C-) was considerably more attenuated than rHPIV1-C(F170S), suggesting that disabling the anti-IFN and antiapoptotic activities of HPIV1 had additive effects on attenuation in vivo. Although rHPIV1-P(C-) protected against challenge with wt HPIV1, its highly restricted replication in AGMs and in primary human airway epithelial cell cultures suggests that it might be overattenuated for use as a vaccine. Thus, the C proteins of HPIV1 are nonessential but have anti-IFN and antiapoptosis activities required for virulence in primates. 相似文献
116.
Minjie Qian Eva Rosenqvist Els Prinsen Frauke Pescheck Ann-Marie Flygare Irina Kalbina Marcel A.K. Jansen ke Strid 《Plant physiology》2021,187(1):378
Ultraviolet (UV) light induces a stocky phenotype in many plant species. In this study, we investigate this effect with regard to specific UV wavebands (UV-A or UV-B) and the cause for this dwarfing. UV-A- or UV-B-enrichment of growth light both resulted in a smaller cucumber (Cucumis sativus L.) phenotype, exhibiting decreased stem and petiole lengths and leaf area (LA). Effects were larger in plants grown in UV-B- than in UV-A-enriched light. In plants grown in UV-A-enriched light, decreases in stem and petiole lengths were similar independent of tissue age. In the presence of UV-B radiation, stems and petioles were progressively shorter the younger the tissue. Also, plants grown under UV-A-enriched light significantly reallocated photosynthates from shoot to root and also had thicker leaves with decreased specific LA. Our data therefore imply different morphological plant regulatory mechanisms under UV-A and UV-B radiation. There was no evidence of stress in the UV-exposed plants, neither in photosynthetic parameters, total chlorophyll content, or in accumulation of damaged DNA (cyclobutane pyrimidine dimers). The abscisic acid content of the plants also was consistent with non-stress conditions. Parameters such as total leaf antioxidant activity, leaf adaxial epidermal flavonol content and foliar total UV-absorbing pigment levels revealed successful UV acclimation of the plants. Thus, the UV-induced dwarfing, which displayed different phenotypes depending on UV wavelengths, occurred in healthy cucumber plants, implying a regulatory adjustment as part of the UV acclimation processes involving UV-A and/or UV-B photoreceptors.A stocky phenotype develops in healthy cucumber plants as a regulatory adjustment toward UV-A and UV-B-enriched light, revealing a strong interaction between UV acclimation and developmental processes. 相似文献
117.
Ksenia Bystrova Ann-Marie Widström Ann-Sofi Matthiesen Anna-Berit Ransjö-Arvidson Barbara Welles-Nyström Igor Vorontsov Kerstin Uvnäs-Moberg 《International breastfeeding journal》2007,2(1):1-14
Background
Research in the field of psychoneuroimmunology (PNI) has revealed that depression is associated with inflammation manifested by increased levels of proinflammatory cytokines.Discussion
The old paradigm described inflammation as simply one of many risk factors for depression. The new paradigm is based on more recent research that has indicated that physical and psychological stressors increase inflammation. These recent studies constitute an important shift in the depression paradigm: inflammation is not simply a risk factor; it is the risk factor that underlies all the others. Moreover, inflammation explains why psychosocial, behavioral and physical risk factors increase the risk of depression. This is true for depression in general and for postpartum depression in particular. Puerperal women are especially vulnerable to these effects because their levels of proinflammatory cytokines significantly increase during the last trimester of pregnancy – a time when they are also at high risk for depression. Moreover, common experiences of new motherhood, such as sleep disturbance, postpartum pain, and past or current psychological trauma, act as stressors that cause proinflammatory cytokine levels to rise. Breastfeeding has a protective effect on maternal mental health because it attenuates stress and modulates the inflammatory response. However, breastfeeding difficulties, such as nipple pain, can increase the risk of depression and must be addressed promptly.Conclusion
PNI research suggests two goals for the prevention and treatment of postpartum depression: reducing maternal stress and reducing inflammation. Breastfeeding and exercise reduce maternal stress and are protective of maternal mood. In addition, most current treatments for depression are anti-inflammatory. These include long-chain omega-3 fatty acids, cognitive therapy, St. John's wort, and conventional antidepressants. 相似文献118.
Natalie Ring Terrence F. Meehan Andrew Blake James Brown Chao-Kung Chen Nathalie Conte Armida Di Fenza Tanja Fiegel Neil Horner Julius O. B. Jacobsen Natasha Karp Thomas Lawson Jeremy C. Mason Peter Matthews Hugh Morgan Mike Relac Luis Santos Damian Smedley Duncan Sneddon Alice Pengelly Ilinca Tudose Jonathan W. G. Warren Henrik Westerberg Gagarine Yaikhom Helen Parkinson Ann-Marie Mallon 《Mammalian genome》2015,26(9-10):413-421
119.
Reid RD Tulloch H Kocourek J Morrin LI Beaton LJ Papadakis S Blanchard CM Riley DL Pipe AL 《Canadian journal of physiology and pharmacology》2007,85(1):17-23
We describe transitions between exercise stages of change in people with coronary artery disease (CAD) over a 6-month period following a CAD-related hospitalization and evaluate constructs from Protection Motivation Theory, Theory of Planned Behavior, Social Cognitive Theory, the Ecological Model, and participation in cardiac rehabilitation as correlates of stage transition. Seven hundred eighty-two adults hospitalized with CAD were recruited and administered a baseline survey including assessments of theory-based constructs and exercise stage of change. Mailed surveys were used to gather information concerning exercise stage of change and participation in cardiac rehabilitation 6 months later. Progression from pre-action stages between baseline and 6 month follow-up was associated with greater perceived efficacy of exercise to reduce risk of future disease, fewer barriers to exercise, more access to home exercise equipment, and participation in cardiac rehabilitation. Regression from already active stages between baseline and 6 month follow-up was associated with increased perceived susceptibility to a future CAD-related event, fewer intentions to exercise, lower self-efficacy, and more barriers to exercise. 相似文献
120.
Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects
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Ellard S Flanagan SE Girard CA Patch AM Harries LW Parrish A Edghill EL Mackay DJ Proks P Shimomura K Haberland H Carson DJ Shield JP Hattersley AT Ashcroft FM 《American journal of human genetics》2007,81(2):375-382
Heterozygous activating mutations in the KCNJ11 gene encoding the pore-forming Kir6.2 subunit of the pancreatic beta cell K(ATP) channel are the most common cause of permanent neonatal diabetes (PNDM). Patients with PNDM due to a heterozygous activating mutation in the ABCC8 gene encoding the SUR1 regulatory subunit of the K(ATP) channel have recently been reported. We studied a cohort of 59 patients with permanent diabetes who received a diagnosis before 6 mo of age and who did not have a KCNJ11 mutation. ABCC8 gene mutations were identified in 16 of 59 patients and included 8 patients with heterozygous de novo mutations. A recessive mode of inheritance was observed in eight patients with homozygous, mosaic, or compound heterozygous mutations. Functional studies of selected mutations showed a reduced response to ATP consistent with an activating mutation that results in reduced insulin secretion. A novel mutational mechanism was observed in which a heterozygous activating mutation resulted in PNDM only when a second, loss-of-function mutation was also present. 相似文献