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1.
We have analyzed the mutational spectra produced during in vitro DNA synthesis by DNA polymerase alpha-primase and DNA polymerase beta. The polymerase mutation frequency as measured in the in vitro herpes simplex virus thymidine kinase (HSV-tk) forward assay was increased when reactions utilized single-stranded DNA templates randomly modified by 20 mM N-ethyl-N-nitrosourea (ENU), relative to solvent-treated templates. A 20- to 50-fold increase in the frequency of G-->A transition mutations was observed for both polymerases, as expected due to mispairing by O6-ethylguanine lesions. Strikingly, ENU treatment of the template also resulted in a five- to 12-fold increased frequency of frameshift errors at heteropolymeric (non-repetitive) template sequences produced by polymerase beta and polymerase alpha-primase, respectively. The increased proportion of frameshift mutations at heteropolymeric sequences relative to homopolymeric (repetitive) sequences produced by each polymerase in response to ENU damage was statistically significant. For polymerase alpha-primase, one-base deletion errors at template guanine residues was the second most frequent mutational event, observed at a frequency only four-fold lower than the G-->A transition frequency. In the polymerase beta reactions, the frequency of insertion errors at homopolymeric (repetitive) sequences was increased six-fold using alkylated templates, relative to solvent controls. The frequency of such insertion errors was only three-fold lower than the frequency of G-->A transition errors by polymerase beta. Although ENU is generally regarded as a potent base substitution mutagen, these data show that monofunctional alkylating agents are capable of inducing frameshift mutations in vitro. Alkylation-induced frameshift mutations occur in both repetitive and non-repetitive DNA sequences; however, the mutational specificity is dependent upon the DNA polymerase.  相似文献   

2.
Intracranial microembolic signals, probably caused by gaseous emboli, are readily detectable in patients undergoing radiofrequency ablation in the left side of the heart only. Clinical value of the detected signals could not be equivocably assessed, because only 2 of the patients who were examined (both emboli positive) had transient neurologic symptoms.  相似文献   

3.
In previous work the authors argued that the potential number of effectors in the response set is crucial in discriminating (multiple-effector) keypress from (single-effector) reaching responses. It is not clear, however, what influence the locus of responding (on vs. off the stimulus location for reaching and keypressing, respectively) has on reaction time (RT) performance. In 3 experiments, the authors systematically manipulated response location and response type using a spatial precuing task. The results consistently showed that even though response location did influence the RTs of keypress and reaching responses, the effect of the number of potential effectors was dominant in shaping the prototypical RT profiles of the 2 response types. These outcomes underscore the importance of the anatomical identity, in addition to response location, in response coding and corroborate the notion that distinct mechanisms dominate performance in single- and multiple-effector visuomotor tasks. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

4.
试验研究熔融还原过程条件下SiO2还原氧化行为及对过程的影响.研究表明:喷吹煤粉燃烧温度、煤的灰份组成影响SiO2还原过程.通过适当选择煤种和控制氧煤喷枪的喷吹位置,可以减轻SiO2还原挥发对过程的不利影响.  相似文献   

5.
When infants first learn to reach at about 4 months, their hand paths are jerky and tortuous, but their reaches become smoother and straighter over the first year. Here the authors consider the role of the underlying limb dynamics, which scale with movement speed, on the development of trajectory control. The authors observed 4 infants weekly and then biweekly from reach onset to 1 yr. Improvements in trajectories were not linear, but showed plateaus and regressions in straightness and smoothness. When infants' nonreaching movements were fast, their reaches were also fast, and faster reaches were also less straight. This is consistent with an equilibrium trajectory form of control, where development involves the increasing ability to stabilize the trajectory against self-generated movement perturbations. (PsycINFO Database Record (c) 2011 APA, all rights reserved)  相似文献   

6.
Transcranial magnetic stimulation (TMS) during positron emission tomography (PET) is a novel technique for in vivo measurements of connectivity and excitability of the human cerebral cortex. Here we describe tools that allow investigators to position the stimulating coil over a target region and to verify the actual position of the coil after the study. The former is achieved by coregistering the head of the subject with an MR image of his/her brain using frameless stereotaxy. The latter is accomplished by identifying the coil on a transmission scan and coregistering it, e.g., with a model of the electrical field induced in the brain.  相似文献   

7.
Noradrenaline and adrenergic agonists were tested on pacemaker-like and silent neurons of the rat rostral ventrolateral medulla using intracellular recording in coronal brainstem slices as well as in punches containing only the rostral ventrolateral medullary region. Noradrenaline (1-100 microM) depolarized or increased the frequency of discharge of all cells tested in a dose-dependent manner. The noradrenaline-induced depolarization was associated with an apparent increase in cell input resistance at low concentrations and a decrease or no significant change at higher concentrations. Moreover, it was voltage dependent and its amplitude decreased with membrane potential hyperpolarization. Noradrenaline caused a dose-related increase in the frequency and amplitude of spontaneous inhibitory postsynaptic potentials. The alpha 1-adrenoceptor antagonist prazosin (0.5 microM) abolished the noradrenaline depolarizing response as well as-the noradrenaline-evoked increase in synaptic activity and unmasked an underlying noradrenaline dose-dependent hyperpolarizing response associated with a decrease in cell input resistance and sensitive to the alpha 2-adrenoceptor/antagonist yohimbine (0.5 microM). The alpha 1-adrenoceptor agonist phenylephrine (10 microM) mimicked the noradrenaline depolarizing response associated with an increase in membrane resistance as well as the noradrenaline-induced increase in synaptic activity. The alpha 2-adrenoceptor agonists UK-14,304 (1-3 microM) and clonidine (10-30 microM) produced only a small hyperpolarizing response, whereas the beta-adrenoceptor agonist isoproterenol (10-30 microM) had no effect. Baseline spontaneous postsynaptic potentials were abolished by strychnine (1 microM), bicuculline (30 microM) or both. However, only the strychnine-sensitive postsynaptic potentials had their frequency increased by noradrenaline or phenylephrine and they usually occurred with a regular pattern. Tetrodotoxin (1 microM) eliminated 80-95% of baseline spontaneous postsynaptic potentials and prevented the increase in synaptic activity evoked by noradrenaline and phenylephrine. Similar results were obtained in rostral ventrolateral medulla neurons impaled in both coronal slices and punches of the rostral ventrolateral medulla. It is concluded that noradrenaline could play an important inhibitory role in the rostral ventrolateral medulla via at least two mechanisms: an alpha 2-adrenoceptor-mediated hyperpolarization and an enhancement of inhibitory synaptic transmission through activation of alpha 1-adrenoceptors located on the somatic membrane of glycinergic interneurons. Some of these interneurons exhibit a regular discharge similar to the pacemaker-like neurons and might, at least in part, constitute a central inhibitory link in the baroreceptor-vasomotor reflex pathway.  相似文献   

8.
Responses to clicks were increased in cartwheel cells of the dorsal cochlear nucleus of cats after pairing presentations of the clicks with local iontophoretic delivery of glutamate. The cells were identified by bursting discharges, and were recorded intracellularly in vivo. The findings indicate that inhibitory interneurons such as cartwheel cells can participate in complex adaptive acoustic signal processing. Each cell displayed doublet discharges of > 800 Hz. In 70% of the cells, some of the doublet discharges reached rates > 1000 Hz.  相似文献   

9.
Gulyaeva  R. I.  Udoeva  L. Yu.  Petrova  S. A.  Sergeeva  S. V.  Pikulin  K. V.  Agafonov  S. N. 《Metallurgist》2022,66(1-2):200-214
Metallurgist - In this study, phase transformations were examined during low temperature interactions of natural tantalite with powders of aluminum and Ca–Al addition alloy (69.4 wt% Ca)...  相似文献   

10.
We recorded reaching movements from nine infants longitudinally from the onset of reaching (5th postnatal month) up to the age of 3 years. Here we analyze hand and proximal joint trajectories and examine the emerging temporal coordination between arm segments. The present investigation seeks (a) to determine when infants acquire consistent, adult-like patterns of multijoint coordination within that 3-year period, and (b) to relate their hand trajectory formation to underlying patterns of proximal joint motion (shoulder, elbow). Our results show: First, most kinematic parameters do not assume adult-like levels before the age of 2 years. At this time, 75% of the trials reveal a single peaked velocity profile of the hand. Between the 2nd and 3rd year of life, "improvements" of hand- or joint-related movement units are only marginal. Second, infant motor systems strive to obtain velocity patterns with as few force reversals as possible (uni- or bimodal) at all three limb segments. Third, the formation of a consistent interjoint synergy between shoulder and elbow motion is not achieved within the 1st year of life. Stable patterns of temporal coordination across arm segments begin to emerge at 12-15 months of age and continue to develop up to the 3rd year. In summary, the development toward adult forms of multijoint coordination in goal-directed reaching requires more time than previously assumed. Although infants reliably grasp for objects within their workspace 3-4 months after the onset of reaching, stereotypic kinematic motor patterns are not expressed before the 2nd year of life.  相似文献   

11.
Recent studies provide further support for the hypothesis that spatial representations of limb position, target locations, and potential motor actions are expressed in the neuronal activity in parietal cortex. In contrast, precentral cortical activity more strongly expresses processes involved in the selection and execution of motor actions. As a general conceptual framework, these processes may be interpreted in terms of such formalisms as sensorimotor transformations and 'internal models'.  相似文献   

12.
13.
Dendritic cells (DCs) are professional antigen-presenting cells (APCs), and classical DCs, such as Langerhans cells (LCs) or interdigitating DCs (IDCs) are known to be the most potent stimulators of T lymphocytes. Earlier, several groups described the generation of DCs from monocytes, starting with peripheral blood mononuclear cells (PBMCs), adherent cells or magnetic bead-purified CD14+ cells. Although modifications of the original protocols have already been described, some questions relevant to clinical application and basic studies have not yet been addressed. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL4) appear to be necessary, but are not sufficient for the differentiation of monocyte-derived dendritic cells (MoDCs), as indicated by the failure to generate such cells under serum-free conditions. Using adherence purified monocytes, we first investigated the amount of GM-CSF and IL4 required for the differentiation of DCs. Consecutive kinetic studies during the differentiation period were designed to demonstrate how monocytes acquire the phenotype and function of DCs. The results showed that small amounts of GM-CSF and IL4 were required to generate MoDC which acquired their phenotype and function within 4 days. IL13 may substitute for IL4, whereas IL10, TNF alpha or IFN gamma inhibited the generation of MoDCs.  相似文献   

14.
Neuroimaging studies have frequently observed relatively high activity in medial rostral prefrontal cortex (PFC) during rest or baseline conditions. Some accounts have attributed this high activity to the occurrence of unconstrained stimulus-independent and task-unrelated thought processes during baseline conditions. Here, the authors investigated the alternative possibility that medial rostral PFC supports attention toward the external environment during low-demand conditions. Participants performed a baseline simple reaction time (RT) task, along with 3 other tasks that differed in the requirement to attend to external stimuli versus stimulus-independent thought. Medial rostral PFC activation was observed in the baseline task and in a condition requiring strong engagement with external stimuli, relative to 2 conditions with a greater requirement for stimulus-independent thought. An important finding was that activity in this region was associated with faster RTs in the baseline task, ruling out an explanation in terms of task-unrelated thought processes during this condition. Thus, at least under certain circumstances, medial rostral PFC appears to support attention toward the external environment, facilitating performance in situations that do not require extensive processing of experimental stimuli. (PsycINFO Database Record (c) 2010 APA, all rights reserved)  相似文献   

15.
为了探讨铬铁矿的熔融还原机理,利用光学显微镜、电子扫描显微镜和能谱分析技术,观察分析熔融滴下实验中不锈钢母液炉料滴下物的结构形态变化。结果表明,还原过程可分为两个阶段:首先是铬铁矿通过CO气体的间接还原,其还原机理可用未反应核模型解释;其后是铬铁矿逐步在渣相中溶解,被固体碳直接熔融还原。  相似文献   

16.
17.
This study compared patterns of parenteral antibiotic treatment by emergency physicians with literature-derived guidelines in the management of wound care. All patients who received parenteral antibiotics as part of wound management in an urban general emergency department (ED) (annual volume 65,000) and did not receive subsequent consultation or admission were prospectively studied for 4 weeks (July 18 to August 15, 1994). Data collected included age, sex, antibiotic, route of administration, dose, cost, diagnosis, and board certification of emergency physician. Antibiotic choice and dose were reviewed by study-blinded physicians and compared with criteria based on a review of the current wound care literature. Wound characteristics justifying antibiotic prophylaxis were derived from the literature and included immunocompromised patient, wounds with debris or occurring under contaminated circumstances, wounds with cellulitis or purulent drainage, wounds older than 18 hours, and crush injuries. The study included 72 patients, and 13 (18%) antibiotic discrepancies were found. Cefazolin (n = 49 [64%]) and ceftriaxone (n = 25 [35%]) were the most commonly prescribed parenteral antibiotics, with cefazolin used in 9 (69%) and ceftriaxone in 4 (31%) of discrepant cases. There were not significant differences in discrepant parenteral antibiotic by emergency physicians' board certification. There were no significant demographic differences between patients receiving discrepant and nondiscrepant antibiotics. The excess cost of discrepant parenteral antibiotics during this small study period was $380. Approximately one fifth of the parenteral antibiotics prescribed during wound care administered in the ED were discrepant with current recommendations derived from the literature.  相似文献   

18.
Mice immunized with plasmid DNA encoding Nef accessory protein of human immunodeficiency virus type 1 developed high levels of anti-Nef antibodies which were maintained for at least 16 months. These antibodies produced in response to Nef-expressing plasmid DNA did not recognize the linear peptides except the long C-terminal peptide for three of the ten sera. With anti-Nef antibodies produced in mice immunized with the protein Nef without any adjuvant, the same restraint epitope binding was found. On the contrary, anti-Nef antibodies from mice immunized with the protein in Freund's adjuvant showed a broader epitope reactivity pattern. Interestingly, the analysis of immunoglobulin isotype profiles of antibodies generated by the different protocols of immunization showed that plasmid DNA immunization induced predominantly IgG2a, whereas immunization with Nef protein, with or without adjuvant, yielded a preponderance of IgG1 antibodies.  相似文献   

19.
20.
Capsaicin (Cap) is a pungent extract of the Capsicum pepper family, which activates nociceptive primary sensory neurons. Inward current and membrane potential responses of cultured neonatal rat dorsal root ganglion neurons to capsaicin were examined using whole-cell and perforated patch recording methods. The responses exhibited strong desensitization operationally classified as acute (diminished response during constant Cap exposure) and tachyphylaxis (diminished response to successive applications of Cap). Both acute desensitization and tachyphylaxis were greatly diminished by reductions in external Ca2+ concentration. Furthermore, chelation of intracellular Ca2+ by addition of either EGTA or bis(2-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid to the patch pipette attenuated both forms of desensitization even in normal Ca2+. Release of intracellular Ca2+ by caffeine triggered acute desensitization in the absence of extracellular Ca2+, and barium was found to effectively substitute for calcium in supporting desensitization. Cap activated inward current at an ED50 of 728 nM, exhibiting cooperativity (Hill coefficient, 2.2); however, both forms of desensitization were only weakly dependent on [Cap], suggesting a dissociation between activation of Cap-sensitive channels and desensitization. Removal of ATP and GTP from the intracellular solutions resulted in nearly complete tachyphylaxis even with intracellular Ca2+ buffered to low levels, whereas changes in nucleotide levels did not significantly alter the acute form of desensitization. These data suggest a key role for intracellular Ca2+ in desensitization of Cap responses, perhaps through Ca2+-dependent dephosphorylation at a locus that normally sustains Cap responsiveness via ATP-dependent phosphorylation. It also seems that the signaling mechanisms underlying the two forms of desensitization are not identical in detail.  相似文献   

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