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971.
Sandoval A Arikkath J Monjaraz E Campbell KP Felix R 《Cellular and molecular neurobiology》2007,27(7):901-908
(1) Voltage-gated Ca2+ (CaV) channels are multi-subunit membrane complexes that allow depolarization-induced Ca2+ influx into cells. The skeletal muscle L-type CaV channels consist of an ion-conducting CaV1.1 subunit and auxiliary α2δ−1, β1 and γ1 subunits. This complex serves both as a CaV channel and as a voltage sensor for excitation–contraction coupling. (2) Though much is known about the mechanisms by which
the α2δ−1 and β1 subunits regulate CaV channel function, there is far less information on the γ1 subunit. Previously, we characterized the interaction of γ1 with the other components of the skeletal CaV channel complex, and showed that heterologous expression of this auxiliary subunit decreases Ca2+ current density in myotubes from γ1 null mice. (3) In the current report, using Western blotting we show that the expression of the CaV1.1 protein is significantly lower when it is heterologously co-expressed with γ1. Consistent with this, patch-clamp recordings showed that transient transfection of γ1 drastically inhibited macroscopic currents through recombinant N-type (CaV2.2/α2δ−1/β3) channels expressed in HEK-293 cells. (4) These findings provide evidence that co-expression of the auxiliary γ1 subunit results in a decreased expression of the ion-conducting subunit, which may help to explain the reduction in Ca2+ current density following γ1 transfection. 相似文献
972.
Christesen HB Brusgaard K Alm J Sjöblad S Hussain K Fenger C Rasmussen L Hovendal C Otonkoski T Jacobsen BB 《Hormone research》2007,67(4):184-188
BACKGROUND: In severe, medically unresponsive congenital hyperinsulinism (CHI), the histological differentiation of focal versus diffuse disease is vital, since the surgical management is completely different. Genetic analysis may help in the differential diagnosis, as focal CHI is associated with a paternal germline ABCC8 or KCNJ11 mutation and a focal loss of maternal chromosome 11p15, whereas a maternal mutation, or homozygous/compound heterozygous ABCC8 and KCNJ11 mutations predict diffuse-type disease. However, genotyping usually takes too long to be helpful in the absence of a founder mutation. METHODS: In 4 patients, a rapid genetic analysis of the ABBC8 and KCNJ11 genes was performed within 2 weeks on request prior to the decision of pancreatic surgery. RESULTS: Two patients had no mutations, rendering the genetic analysis non-informative. Peroperative multiple biopsies showed diffuse disease. One patient had a paternal KCNJ11 mutation and focal disease confirmed by positron emission tomography scan and biopsies. One patient had a de novo heterozygous ABBC8 mutation and unexplained diffuse disease confirmed by positron emission tomography scan and biopsies. CONCLUSION: A rapid analysis of the entire ABBC8 and KCNJ11 genes should not stand alone in the preoperative assessment of patients with CHI, except for the case of maternal, or homozygous/compound heterozygous disease-causing mutations. 相似文献
973.
Breast-fed preterm infants often show a better outcome, partly ascribed to the benefit of insulin-like growth factors (IGFs) and their binding proteins (IGFBP). We compared IGF-I, IGF-II, IGFBP-2 and IGFBP-3 levels, measured by radioimmunoassays in milk samples from 30 mothers of preterm (<31 weeks) and from 19 mothers of term (>37 weeks) infants at days 7 and 21 postpartum. Proteolysis of IGFBP-2 within mother's milk and digestion of (125)I-IGF-II and (125)I-IGFBP-2 by gastric juice from neonates were assessed by electrophoretic techniques. Mean concentrations did not differ between preterm and term milk: IGF-I (2.8 +/- 0.2 vs. 2.3 +/- 0.1 ng/ml), IGF-II (12.0 +/- 0.4 vs. 12.2 +/- 0.5 ng/ml), IGFBP-3 (100.0 +/- 5.1 vs. 80.0 +/- 5.8 ng/ml), but did so for IGFBP-2 (3,144 +/- 172 vs. 2,428 +/- 188 ng/ml, p < 0.02). Immunoblots revealed 42% (p < 0.05) more IGFBP-2 fragments of 14 and 25 kDa in preterm milk. Incubation with gastric juice caused cleavage of (125)I-IGFBP-2 and partial cleavage of (125)I-IGF-II. Mutual complexation protected IGF-II and IGFBP-2 from cleavage, suggesting that both are likely to arrive in the bowel in an intact form to exert promotive effects. The results provide further evidence that IGFBP-2 and IGF-II in breast milk are relevant factors for the early development of preterm infants. 相似文献
974.
Müller WE Eckert C Kropf K Wang X Schlossmacher U Seckert C Wolf SE Tremel W Schröder HC 《Cell and tissue research》2007,329(2):363-378
The siliceous sponge Monorhaphis chuni (Hexactinellida) synthesizes the largest biosilica structures on earth (3 m). Scanning electron microscopy has shown that
these spicules are regularly composed of concentrically arranged lamellae (width: 3–10 μm). Between 400 and 600 lamellae have
been counted in one giant basal spicule. An axial canal (diameter: ~2 μm) is located in the center of the spicules; it harbors
the axial filament and is surrounded by an axial cylinder (100–150 μm) of electron-dense homogeneous silica. During dissolution
of the spicules with hydrofluoric acid, the axial filament is first released followed by the release of a proteinaceous tubule.
Two major proteins (150 kDa and 35 kDa) have been visualized, together with a 24-kDa protein that cross-reacts with antibodies
against silicatein. The spicules are surrounded by a collagen net, and the existence of a hexactinellidan collagen gene has
been demonstrated by cloning it from Aphrocallistes vastus. During the axial growth of the spicules, silicatein or the silicatein-related protein is proposed to become associated with
the surface of the spicules and to be finally internalized through the apical opening to associate with the axial filament.
Based on the data gathered here, we suggest that, in the Hexactinellida, the growth of the spicules is mediated by silicatein
or by a silicatein-related protein, with the orientation of biosilica deposition being controlled by lectin and collagen.
Carsten Eckert was previously with the Museum für Naturkunde, Invalidenstrasse 43, 10115 Berlin, Germany.
The collagen sequence from Aphrocallistes vastus reported here, viz., [COL_APHRO] APHVACOL (accession number AM411124), has been deposited in the EMBL/GenBank data base.
This work was supported by grants from the European Commission, the Deutsche Forschungsgemeinschaft, the Bundesministerium
für Bildung und Forschung Germany (project: Center of Excellence BIOTECmarin), the National Natural Science Foundation of China (grant no. 50402023), and the International Human Frontier Science
Program. 相似文献
975.
Döring B Pfitzer G Adam B Liebregts T Eckardt D Holtmann G Hofmann F Feil S Feil R Willecke K 《Cell and tissue research》2007,327(2):333-342
Connexin43 (Cx43) gap-junction channels are highly abundant in intestinal smooth muscle but their functional impact has not
been studied so far. Here, we have aimed to elucidate the functional role of Cx43 in the tunica muscularis of the mouse intestine
in vivo. Transgenic mice with conditional deletion of Cx43 in smooth muscle cells (SMC) were generated. Histological investigations
by immunofluorescence analyses and organ-bath recordings to assess the contractility of intestinal tissue strips were carried
out. Measurements of gastrointestinal transit and of the visceromotor response by utilizing a standardized colorectal distension
model to quantify alterations of visceral sensory function were also performed in SMC-specific Cx43 null mice and control
littermates. Histologically, we found thickening of the tunica muscularis and a 13-fold increase of neutrophil infiltration
of the gastrointestinal wall of SMC-specific Cx43 null mice. These animals also exhibited a decrease of 29% in gastrointestinal
transit time. In contrast, the visceromotor response to a standardized colorectal distension was elevated, as was the contractility
in SMC-specific Cx43 null mice, compared with controls. Thus, SMC-specific ablation of Cx43 in mice leads to morphological
and functional alterations of the intestinal tunica muscularis, to gastrointestinal motor dysfunction and to altered visceral
sensory function.
This study was supported by a grant from the German Research Association (Wi 270/25-1,2) to K.W. and in part by the IFORES
program of the University Hospital, Essen, Germany. 相似文献
976.
977.
Sexual conflict can produce several evolutionary outcomes, one of which is female-limited trait polymorphism. We examine the African bat bug Afrocimex constrictus (Cimicidae), a species where both sexes are subjected to traumatic intromission from males. We show that males possess female genital structures that in related species ameliorate the costs of traumatic insemination. Moreover, the male form of these structures differs morphologically from the standard female form. Examination of females in our isolated study population revealed a discrete polymorphism in female genitalia. Some females had the typical cimicid form, while others had genitalia that more closely resembled the distinctive male form. Males, as well as females with the distinctive male form, experienced fewer traumatic copulations than the typical female morph. We propose that some females mimic the bizarre male condition in order to reduce the frequency of costly traumatic inseminations. To our knowledge this is the first example of a distinct female-limited genital polymorphism: its nature, as well as its association with traumatic sexual interactions, strongly suggests that sexual conflict underpins this unique phenomenon. 相似文献
978.
Xi Chen Jörg Andrä Walter Richter Alan M. Krensky Klaus Brandenburg 《生物化学与生物物理学报:生物膜》2007,1768(10):2421-2431
To combat infections by Gram-negative bacteria, it is not only necessary to kill the bacteria but also to neutralize pathogenicity factors such as endotoxin (lipopolysaccharide, LPS). The development of antimicrobial peptides based on mammalian endotoxin-binding proteins is a promising tool in the fight against bacterial infections, and septic shock syndrome. Here, synthetic peptides derived from granulysin (Gra-pep) were investigated in microbiological and biophysical assays to understand their interaction with LPS. We analyzed the influence of the binding of Gra-pep on (1) the acyl chain melting of the hydrophobic moiety of LPS, lipid A, by Fourier-transform spectroscopy, (2) the aggregate structure of LPS by small-angle X-ray scattering and cryo-transmission electron microscopy, and 3) the enthalpy change by isothermal titration calorimetry. In addition, the influence of Gra-pep on the incorporation of LPS and LPS-LBP (lipopolysaccharide-binding protein) complexes into negatively charged liposomes was monitored. Our findings demonstrate a characteristic change in the aggregate structure of LPS into multilamellar stacks in the presence of Gra-pep, but little or no change of acyl chain fluidity. Neutralization of LPS by Gra-pep is not due to a scavenging effect in solution, but rather proceeds after incorporation into target membranes, suggesting a requisite membrane-bound step. 相似文献
979.
Reconciling strong stabilizing selection with the maintenance of genetic variation in a natural population of black field crickets (Teleogryllus commodus) 总被引:1,自引:0,他引:1
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Genetic variation in single traits, including those closely related to fitness, is pervasive and generally high. By contrast, theory predicts that several forms of selection, including stabilizing selection, will eliminate genetic variation. Stabilizing selection in natural populations tends to be stronger than that assumed in theoretical models of the maintenance of genetic variation. The widespread presence of genetic variation in the presence of strong stabilizing selection is a persistent problem in evolutionary genetics that currently has no compelling explanation. The recent insight that stabilizing selection often acts most strongly on trait combinations via correlational selection may reconcile this problem. Here we show that for a set of male call properties in the cricket Teleogryllus commodus, the pattern of multivariate stabilizing sexual selection is closely associated with the degree of additive genetic variance. The multivariate trait combinations experiencing the strongest stabilizing selection harbored very little genetic variation while combinations under weak selection contained most of the genetic variation. Our experiment provides empirical support for the prediction that a small number of trait combinations experiencing strong stabilizing selection will have reduced genetic variance and that genetically independent trait combinations experiencing weak selection can simultaneously harbor much higher levels of genetic variance. 相似文献
980.
Knott ML Matthaei KI Giacomin PR Wang H Foster PS Dent LA 《International journal for parasitology》2007,37(12):1367-1378
Eosinophils are an important feature of immune responses to infections with many of the tissue-invasive helminth parasites. The cytokine IL-5 and a high-affinity double GATA-binding site within the GATA-1 promoter are critical for eosinophilopoiesis. In this study, we believe we demonstrate for the first time that defects in eosinophilopoiesis are associated with impaired resistance to Nippostrongylus brasiliensis. Primary and secondary infections were established in wildtype (WT), IL-5(-/-) and DeltadblGATA mice. Resistance to secondary infections was impaired in IL-5(-/-) and DeltadblGATA mice, with significantly more larvae able to reach the lungs 2 days p.i. Pulmonary inflammation was minimal in all strains in the first 2 days of both primary and secondary infections, suggesting that eosinophil-dependent resistance occurred before larvae reached this site. Intestinal worm burdens and/or parasite egg production in primary infections were greater in animals with defective eosinophilopoiesis. While larvae did reach the gut by day 3 of secondary infections of WT and IL-5(-/-) mice, worms were expelled by day 7, even in the complete absence of eosinophils in tissues of the small intestine. This and our previous studies indicate that N. brasiliensis are likely to be exquisitely sensitive to attack by eosinophils soon after entry into the skin. Eosinophils in the gut may make a modest contribution to resistance on first exposure to the parasite, but are not required for expulsion in either primary or secondary infections. In order to mount an effective immune response it may be vital for the host to identify and attack the parasite before it implements immune evasion strategies and migrates to other anatomical sites. These observations may be of particular significance for the development of successful vaccines against hookworms and other nematodes. 相似文献