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21.
TM?Matthews RK?Duncan M?Zidanic TH?Michael PA?FuchsEmail author 《Journal of comparative physiology. A, Neuroethology, sensory, neural, and behavioral physiology》2005,191(6):491-503
In the inner ear of birds, as in mammals, reptiles and amphibians, acetylcholine released from efferent neurons inhibits hair cells via activation of an apamin-sensitive, calcium-dependent potassium current. The particular potassium channel involved in avian hair cell inhibition is unknown. In this study, we cloned a small-conductance, calcium-sensitive potassium channel (gSK2) from a chicken cochlear library. Using RT-PCR, we demonstrated the presence of gSK2 mRNA in cochlear hair cells. Electrophysiological studies on transfected HEK293 cells showed that gSK2 channels have a conductance of approximately 16 pS and a half-maximal calcium activation concentration of 0.74±0.17 M. The expressed channels were blocked by apamin (IC50=73.3±5.0 pM) and d-tubocurarine (IC50=7.6±1.0 M), but were insensitive to charybdotoxin. These characteristics are consistent with those reported for acetylcholine-induced potassium currents of isolated chicken hair cells, suggesting that gSK2 is involved in efferent inhibition of chicken inner ear. These findings imply that the molecular mechanisms of inhibition are conserved in hair cells of all vertebrates. 相似文献
22.
Anchoori RK Khan SR Sueblinvong T Felthauser A Iizuka Y Gavioli R Destro F Isaksson Vogel R Peng S Roden RB Bazzaro M 《PloS one》2011,6(8):e23888
Cervical cancer cells exhibit an increased requirement for ubiquitin-dependent protein degradation associated with an elevated metabolic turnover rate, and for specific signaling pathways, notably HPV E6-targeted degradation of p53 and PDZ proteins. Natural compounds with antioxidant properties including flavonoids and triterpenoids hold promise as anticancer agents by interfering with ubiquitin-dependent protein degradation. An increasing body of evidence indicates that their α-β unsaturated carbonyl system is the molecular determinant for inhibition of ubiquitin-mediated protein degradation up-stream of the catalytic sites of the 20S proteasome. Herein we report the identification and characterization of a new class of chalcone-based, potent and cell permeable chemical inhibitors of ubiquitin-dependent protein degradation, and a lead compound RAMB1. RAMB1 inhibits ubiquitin-dependent protein degradation without compromising the catalytic activities of the 20S proteasome, a mechanism distinct from that of Bortezomib. Treatment of cervical cancer cells with RAMB1 triggers unfolded protein responses, including aggresome formation and Hsp90 stabilization, and increases p53 steady state levels. RAMB1 treatment results in activation of lysosomal-dependent degradation pathways as a mechanism to compensate for increasing levels of poly-ubiquitin enriched toxic aggregates. Importantly, RAMB1 synergistically triggers cell death of cervical cancer cells when combined with the lysosome inhibitor Chloroquine. 相似文献
23.
Ahmet Sinan SARI Emre DEMRAY Ahmet
ZTÜRK Ayen TERZ Erdal KARA
Z 《Turkish Journal of Biology》2021,45(3):301
Selective targeting of transfected mesenchymal stem cells (MSCs) carrying specific antioncogenes to the tumor was suggested as a treatment option. Bone morphogenetic protein-2 (BMP2) was shown to inhibit the proliferation and aggressiveness of osteosarcoma (OS) cells. Here, we aimed to assess the homing efficiency of intraperitoneally administered hMSCs transfected with BMP2 to the tumoral site and their effects on OS using an orthotopic xenograft murine model. Orthotopic xenograft murine model of OS in six-week-old female NOD/SCID mice using 143B cells was established. hMSCs transfected with BMP2 (BMP2+hMSC) were used. In vivo experiments performed on four groups of mice that received no treatment, or intraperitoneally administered BMP2, hMSCs, and BMP2+hMSCs. Histopathological and immunohistochemical studies were used to evaluate the pathological identification and to assess the dimensions and necrotic foci of the tumor, the features of lung metastases, and immunostaining against p27, Ki-67, and caspase-3 antibodies. The osteogenic differentiation markers BMP2, BMP4, COL1A1, OPN, OCN and PF4 evaluated using RT-PCR. The tumor dimensions in the hMSCs group were significantly higher than those of the remaining groups (p < 0.01). The number of metastatic foci in the BMP2+hMSCs group was significantly lower than those of the other groups (p < 0.01). The current results showed that the intraperitoneal route could be efficiently used for targeting hMSCs to the tumoral tissues for effective BMP2 delivery. In this study, the effects of BMP2 transfected hMSCs on human OS and metastasis were promising for achieving osteogenic differentiation and reduced metastatic process. 相似文献
24.
Opportunistic fungal infections increase morbidity and mortality in COVID-19 patients monitored in intensive care units (ICU). As patients’ hospitalization days in the ICU and intubation period increase, opportunistic infections also increase, which prolongs hospital stay days and elevates costs. The study aimed to describe the profile of fungal infections and identify the risk factors associated with mortality in COVID-19 intensive care patients. The records of 627 patients hospitalized in ICU with the diagnosis of COVID-19 were investigated from electronic health records and hospitalization files. The demographic characteristics (age, gender), the number of ICU hospitalization days and mortality rates, APACHE II scores, accompanying diseases, antibiotic-steroid treatments taken during hospitalization, and microbiological results (blood, urine, tracheal aspirate samples) of the patients were recorded. Opportunistic fungal infection was detected in 32 patients (5.10%) of 627 patients monitored in ICU with a COVID-19 diagnosis. The average APACHE II score of the patients was 28 ± 6. While 25 of the patients (78.12%) died, seven (21.87%) were discharged from the ICU. Candida parapsilosis (43.7%) was the opportunistic fungal agent isolated from most blood samples taken from COVID-19 positive patients. The mortality rate of COVID-19 positive patients with candidemia was 80%. While two out of the three patients (66.6%) for whom fungi were grown from their tracheal aspirate died, one patient (33.3%) was transferred to the ward. Opportunistic fungal infections increase the mortality rate of COVID-19-positive patients. In addition to the risk factors that we cannot change, invasive procedures should be avoided, constant blood sugar regulation should be applied, and unnecessary antibiotics use should be avoided. 相似文献
25.
Kuzoff RK; Sweere JA; Soltis DE; Soltis PS; Zimmer EA 《Molecular biology and evolution》1998,15(3):251-263
18S ribosomal RNA genes are the most widely used nuclear sequences for
phylogeny reconstruction at higher taxonomic levels in plants. However, due
to a conservative rate of evolution, 18S rDNA alone sometimes provides too
few phylogenetically informative characters to resolve relationships
adequately. Previous studies using partial sequences have suggested the
potential of 26S or large-subunit (LSU) rDNA for phylogeny retrieval at
taxonomic levels comparable to those investigated with 18S rDNA. Here we
explore the patterns of molecular evolution of entire 26S rDNA sequences
and their impact on phylogeny retrieval. We present a protocol for PCR
amplification and sequencing of entire (approximately 3.4 kb) 26S rDNA
sequences as single amplicons, as well as primers that can be used for
amplification and sequencing. These primers proved useful in angiosperms
and Gnetales and likely have broader applicability. With these protocols
and primers, entire 26S rDNA sequences were generated for a diverse array
of 15 seed plants, including basal eudicots, monocots, and higher eudicots,
plus two representatives of Gnetales. Comparisons of sequence dissimilarity
indicate that expansion segments (or divergence domains) evolve 6.4 to 10.2
times as fast as conserved core regions of 26S rDNA sequences in plants.
Additional comparisons indicate that 26S rDNA evolves 1.6 to 2.2 times as
fast as and provides 3.3 times as many phylogenetically informative
characters as 18S rDNA; compared to the chloroplast gene rbcL, 26S rDNA
evolves at 0.44 to 1.0 times its rate and provides 2.0 times as many
phylogenetically informative characters. Expansion segment sequences
analyzed here evolve 1.2 to 3.0 times faster than rbcL, providing 1.5 times
the number of informative characters. Plant expansion segments have a
pattern of evolution distinct from that found in animals, exhibiting less
cryptic sequence simplicity, a lower frequency of insertion and deletion,
and greater phylogenetic potential.
相似文献
26.
ARNE MOKSNES EIVIN RØSKAFT LISE GREGER HAGEN MARCEL HONZA CECILIE MØRK PER H. OLSEN 《Ibis》2000,142(2):247-258
This study is based on continuous video recordings made at 53 Reed Warbler Acrocephalus scirpaceus nests each day during the laying period. Egg-laying by the Common Cuckoo Cuculus canorus was recorded in 14 (26.4%) of these nests. By analysing the activity of the host birds around and at the nest, we found that this is probably not the only cue used by the Common Cuckoo when locating suitable nests to parasitize. Furthermore, in most cases there was no significant difference between the length of time the host birds spent at the nest in the morning and afternoon, thus providing little support for the hypothesis that the Common Cuckoo lays in the afternoon because it is less likely to be seen by the nest owners then. Parasitized Reed Warblers rejected the Common Cuckoo egg more frequently when they observed the parasite at their nests. However, contrary to what should be expected, most Common Cuckoos laid their eggs in the presence of the host(s), and in general their egg-laying behaviour (for example duration of stay at the nest) was less secretive than described earlier. When partially depredating host clutches, Cuckoos showed the same behavioural pattern at parasitized and unparasitized nests, indicating that the latter may act as a potential reserve for egg-laying. 相似文献
27.
Patterns of differentiation and hybridization in North American wolflike canids, revealed by analysis of microsatellite loci 总被引:8,自引:0,他引:8
Roy MS; Geffen E; Smith D; Ostrander EA; Wayne RK 《Molecular biology and evolution》1994,11(4):553-570
Genetic divergence and gene flow among closely related populations are
difficult to measure because mutation rates of most nuclear loci are so low
that new mutations have not had sufficient time to appear and become fixed.
Microsatellite loci are repeat arrays of simple sequences that have high
mutation rates and are abundant in the eukaryotic genome. Large population
samples can be screened for variation by using the polymerase chain
reaction and polyacrylamide gel electrophoresis to separate alleles. We
analyzed 10 microsatellite loci to quantify genetic differentiation and
hybridization in three species of North American wolflike canids. We
expected to find a pattern of genetic differentiation by distance to exist
among wolflike canid populations, because of the finite dispersal distances
of individuals. Moreover, we predicted that, because wolflike canids are
highly mobile, hybrid zones may be more extensive and show substantial
changes in allele frequency, relative to nonhybridizing populations. We
demonstrate that wolves and coyotes do not show a pattern of genetic
differentiation by distance. Genetic subdivision in coyotes, as measured by
theta and Gst, is not significantly different from zero, reflecting
persistent gene flow among newly established populations. However, gray
wolves show significant subdivision that may be either due to drift in past
Ice Age refugia populations or a result of other causes. Finally, in areas
where gray wolves and coyotes hybridize, allele frequencies of gray wolves
are affected, but those of coyotes are not. Past hybridization between the
two species in the south-central United States may account for the origin
of the red wolf.
相似文献
28.
Background
Inbreeding can slow population growth and elevate extinction risk. A small number of unrelated immigrants to an inbred population can substantially reduce inbreeding and improve fitness, but little attention has been paid to the sex-specific effects of immigrants on such "genetic rescue". We conducted two subsequent experiments to investigate demographic consequences of inbreeding and genetic rescue in guppies. 相似文献29.
Diabetes mellitus is a heterogeneous metabolic disorder characterized by hyperglycaemia resulting in defective insulin secretion,
resistance to insulin action or both. The use of biguanides, sulphonylurea and other drugs are valuable in the treatment of
diabetes mellitus; their use, however, is restricted by their limited action, pharmaco-kinetic properties, secondary failure
rates and side effects. Trigonella foenum-graecum, commonly known as fenugreek, is a plant that has been extensively used as a source of antidiabetic compounds from its seeds
and leaf extracts. Preliminary human trials and animal experiments suggest possible hypoglycaemic and anti-hyperlipedemic
properties of fenugreek seed powder taken orally. Our results show that the action of fenugreek in lowering blood glucose
levels is almost comparable to the effect of insulin. Combination with trace metal showed that vanadium had additive effects
and manganese had additive effects with insulin on in vitro system in control and diabetic animals of young and old ages using adipose tissue. The Trigonella and vanadium effects were studied in a number of tissues including liver, kidney, brain peripheral nerve, heart, red blood
cells and skeletal muscle. Addition of Trigonella to vanadium significantly removed the toxicity of vanadium when used to reduce blood glucose levels. Administration of the
various combinations of the antidiabetic compounds to diabetic animals was found to reverse most of the diabetic effects studied
at physiological, biochemical, histochemical and molecular levels. Results of the key enzymes of metabolic pathways have been
summarized together with glucose transporter, Glut-4 and insulin levels. Our findings illustrate and elucidate the antidiabetic/insulin
mimetic effects of Trigonella, manganese and vanadium. 相似文献
30.
Marije Oosting Kathrin Buffen Subbarao RK Malireddi Patrick Sturm Ineke Verschueren Marije I Koenders Frank L van de Veerdonk Jos WM van der Meer Mihai G Netea Thirumala-Devi Kanneganti Leo AB Joosten 《Arthritis research & therapy》2012,14(6):R247