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1.
Electrophysiological effects produced by selective activation of M3 cholinoreceptors were studied in isolated left atrium preparations from rat using the standard sharp glass microelectrode technique. The stimulation of M3 receptors was obtained by application of muscarinic agonist pilocarpine (10?5 M) in the presence of selective M2 antagonist methoctramine (10?7 M). Stimulation of M3 receptors induced marked reduction of action potential duration by 14.4 ± 2.4% and 16.1 ± 2.5% of control duration measured at 50 and 90% of repolarization, respectively. This effect was completely abolished by selective M3 blocker 4-DAMP (10?8 M). In isolated myocytes obtained from the rat left atrium, similar pharmacological stimulation of M3 receptors led to suppression of peak L-type calcium current by 13.9 ± 2.6% of control amplitude (measured at +10 mV), but failed to affect K+ currents I to, I Kur, and I Kir. In the absence of M2 blocker methoctramine, pilocarpine (10?5 M) produced stronger attenuation of I CaL and induced an increase in I Kir. This additive inward rectifier current could be abolished by highly selective blocker of Kir3.1/3.4 channels tertiapin-Q (10?6 M) and therefore was identified as I KACh. Thus, in the rat atrial myocardium activation of M3 receptors leads to shortening of action potentials via suppression of I CaL, but does not enhance the major potassium currents involved in repolarization. Joint stimulation of M2 and M3 receptors produces stronger action potential shortening due to M2-mediated activation of I KACh.  相似文献   
2.
Physiological and behavioural constraints hinder albino individuals. Albino animals are rare in the wild; this trait is associated with easy detection by predators, non-native or damaged environments, and exclusively aphotic environments in total darkness. The social aspect of albinism is reported only for human beings, and the effect is distinguishable in time and space when social benefits, are used to a limited the extent. Thus far, the social consequences of albinism for animals remain unknown. We used socially established groups of the pigmented catfish, (Silurus glanis), to observe space and temporal distance detachment of albino specimens in laboratory conditions. The albino fish were separated at larger distances from the group than pigmented individuals with the same social status determined by familiarity, and this asymmetry also varied in time. Albinism-related ostracism results in a solitary existence, usually followed by enhanced predation risk. The motivation for an individual’s exclusion from a group appears to be the avoidance of the predation risk that increases not only for an odd individual but also for conspecifics within a group. Our findings indicate a role for albinism in behavioural processes related to sociality in a group of conspecifics.  相似文献   
3.
The extreme body sizes of megafishes associated with their high commercial values and recreational interests have made them highly threatened in their native range worldwide by human-induced impacts such as overexploitation. Meanwhile, some megafishes have been introduced outside of their native range. A notable example is the European catfish (Silurus glanis), one of the few siluriforms native to Eastern Europe. It is among the 20 largest freshwater fish worldwide, attaining a total length over 2.7 m and a documented mass of 130 kg. Its distinct phylogeny and extreme size imply many features that are rare among other European fish, including novel behaviours (massive aggregations, beaching), consumption of large bodied prey, fast growth rates, long lifespan, high fecundity, nest guarding and large egg sizes. The spread of the species is likely to continue due to illegal introductions, primarily for recreational angling, coupled with natural range extension associated with climate change. Here, the most recent knowledge on the current distribution and the ecology of the species are reviewed. A series of key research questions are identified that should stimulate new research on this intriguing, yet largely unknown, species and, more generally, on the ecology of freshwater invaders.  相似文献   
4.
The successional dental lamina (SDL) plays an essential role in the development of replacement teeth in diphyodont and polyphyodont animals. A morphologically similar structure, the rudimental successional dental lamina (RSDL), has been described in monophyodont (only one tooth generation) lizards on the lingual side of the developing functional tooth. This rudimentary lamina regresses, which has been proposed to play a role in preventing the formation of future generations of teeth. A similar rudimentary lingual structure has been reported associated with the first molar in the monophyodont mouse, and we show that this structure is common to all murine molars. Intriguingly, a lingual lamina is also observed on the non-replacing molars of other diphyodont mammals (pig and hedgehog), initially appearing very similar to the successional dental lamina on the replacing teeth. We have analyzed the morphological as well as ultrastructural changes that occur during the development and loss of this molar lamina in the mouse, from its initiation at late embryonic stages to its disappearance at postnatal stages. We show that loss appears to be driven by a reduction in cell proliferation, down-regulation of the progenitor marker Sox2, with only a small number of cells undergoing programmed cell death. The lingual lamina was associated with the dental stalk, a short epithelial connection between the tooth germ and the oral epithelium. The dental stalk remained in contact with the oral epithelium throughout tooth development up to eruption when connective tissue and numerous capillaries progressively invaded the dental stalk. The buccal side of the dental stalk underwent keratinisation and became part of the gingival epithelium, while most of the lingual cells underwent programmed cell death and the tissue directly above the erupting tooth was shed into the oral cavity.  相似文献   
5.
6.
Whilst studies have shown that climatic (North Atlantic Oscillation (NAO)) and biotic (acorn production) factors influence rodent populations, mechanisms driving temporal and spatial fluctuation of rodent populations are understudied. This study evaluates relationships between the influence of environmental factors (biotic and abiotic) and phenotypic characteristics across two rodent feeding guilds (granivorous and non-granivorous species) represented by four species of rodents in Central Europe. We hypothesise that the relationship between acorn density and population growth rate are indirectly affected by climatic factors (winter NAO) and that these effects differ amongst herbivorous and granivorous species. In addition, we also tested whether effects of weather and competition on individual phenotype characteristic vary amongst mast and non-mast years. Rodent populations were estimated by catching individuals in snap traps during the growing season (from March to November) over a period of 9 years at three sites. The results of the generalised linear model provide evidence that acorn production best explained the population fluctuations. We therefore conclude that the between-year population fluctuations in rodent abundance were governed by density dependence and initiated primarily by acorn mast years. Auto-regressive models also revealed direct density dependence in combination with the direct effects of mast years. Therefore, strong intraspecific competition for food is likely in years following mast years. Our results also showed that abundance of non-granivorous species is mainly influenced by local weather conditions which could regulate food quality and abundance. On the other hand, population dynamics of granivorous species are caused directly by acorn density and indirectly by climatic condition influencing acorn production.  相似文献   
7.
Antimicrobial photodynamic inactivation is currently being widely considered as alternative to antibiotic chemotherapy of infective diseases, attracting much attention to design of novel effective photosensitizers. Carboranyl-chlorin-e6 (the conjugate of chlorin e6 with carborane), applied here for the first time for antimicrobial photodynamic inactivation, appeared to be much stronger than chlorin e6 against Gram-positive bacteria, such as Bacillus subtilis, Staphyllococcus aureus and Mycobacterium sp. Confocal fluorescence spectroscopy and membrane leakage experiments indicated that bacteria cell death upon photodynamic treatment with carboranyl-chlorin-e6 is caused by loss of cell membrane integrity. The enhanced photobactericidal activity was attributed to the increased accumulation of the conjugate by bacterial cells, as evaluated both by centrifugation and fluorescence correlation spectroscopy. Gram-negative bacteria were rather resistant to antimicrobial photodynamic inactivation mediated by carboranyl-chlorin-e6. Unlike chlorin e6, the conjugate showed higher (compared to the wild-type strain) dark toxicity with Escherichia coli ΔtolC mutant, deficient in TolC-requiring multidrug efflux transporters.  相似文献   
8.
Insight into the aberrant expression of microRNAs (miRNAs) and the genes that they regulate during the progression of cancer in general and prostate cancer (PCa) in particular is one of the most important issues in current molecular biomedicine and allows for the discovery of therapeutic or diagnostic miRNA targets. The present study aimed to analyze the available data regarding the direct or indirect effects of miRNAs on the expression of the mRNAs involved in carcinogenesis and to enable updating and optimizing the selection of the corresponding targets. The present review focuses on the data related to the genes with miRNA‐dependent expression during the development of PCa. The data used in this review have been extracted from research papers and the databases STRING, PANTHER and TargetScan, with a special focus on the genes directly associated with cell transformation and the maintenance of the transformed genotype, as well as tumor invasion and spread. The search for miRNA markers of PCa and therapeutically active molecules should rely on bioinformatics resources, such as data from recent experimental studies, as well as meta‐analysis and cross‐analysis of the data on the state of the tumor, patient status, histological/immunohistological data and data on mRNA–miRNA coexpression.  相似文献   
9.
Propofol acts as a positive allosteric modulator of γ-aminobutyric acid type A receptors (GABAARs), an interaction necessary for its anesthetic potency in vivo as a general anesthetic. Identifying the location of propofol-binding sites is necessary to understand its mechanism of GABAAR modulation. [3H]2-(3-Methyl-3H-diaziren-3-yl)ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate (azietomidate) and R-[3H]5-allyl-1-methyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid (mTFD-MPAB), photoreactive analogs of 2-ethyl 1-(phenylethyl)-1H-imidazole-5-carboxylate (etomidate) and mephobarbital, respectively, have identified two homologous but pharmacologically distinct classes of intersubunit-binding sites for general anesthetics in the GABAAR transmembrane domain. Here, we use a photoreactive analog of propofol (2-isopropyl-5-[3-(trifluoromethyl)-3H-diazirin-3-yl]phenol ([3H]AziPm)) to identify propofol-binding sites in heterologously expressed human α1β3 GABAARs. Propofol, AziPm, etomidate, and R-mTFD-MPAB each inhibited [3H]AziPm photoincorporation into GABAAR subunits maximally by ∼50%. When the amino acids photolabeled by [3H]AziPm were identified by protein microsequencing, we found propofol-inhibitable photolabeling of amino acids in the β3-α1 subunit interface (β3Met-286 in β3M3 and α1Met-236 in α1M1), previously photolabeled by [3H]azietomidate, and α1Ile-239, located one helical turn below α1Met-236. There was also propofol-inhibitable [3H]AziPm photolabeling of β3Met-227 in βM1, the amino acid in the α1-β3 subunit interface photolabeled by R-[3H]mTFD-MPAB. The propofol-inhibitable [3H]AziPm photolabeling in the GABAAR β3 subunit in conjunction with the concentration dependence of inhibition of that photolabeling by etomidate or R-mTFD-MPAB also establish that each anesthetic binds to the homologous site at the β3-β3 subunit interface. These results establish that AziPm as well as propofol bind to the homologous intersubunit sites in the GABAAR transmembrane domain that binds etomidate or R-mTFD-MPAB with high affinity.  相似文献   
10.
This work presents a comparative study of proton transfer activity (PTA) of two cationic (+6) antimicrobial peptides, β‐structural arenicin‐2 and α‐helical melittin. A new approach was proposed for the detection of passive proton transfer by using proteoliposomes containing bacteriorhodopsin, which creates a small light‐induced electrochemical proton gradient ?ΔpH. Addition of several nanomoles of the peptides lowers ?ΔpH that is proximately indicative of the pore formation. The quantitative analysis of sigmoidal dependences of ?pH on the peptides concentration was carried out using liposomes prepared from PC, PC/PE, PC/PE/PI and PC/PG. Substitution of PC‐containing liposomes with PE‐containing ones, having negative spontaneous curvature, reduced the PTA of α‐helical melittin and increased that of β‐structural arenicin‐2. This result indicates an essential difference in the pore formation by these peptides. Further increase of PTA in response to arenicin‐2 (in contrast to melittin) was observed in the liposomes prepared from PC/PE/PI. The data analysis leads to the conclusion that PTA is influenced by (i) efficiency of the pore assemblage, which depends on the structure of pore‐forming peptides, and the spontaneous curvature of lipids and (ii) the presence of mobile protons in the polar head groups of phospholipids. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd.  相似文献   
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