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At least 73 records · Page 4Linked to original sources
PubMed1992

The development of a new small-scale smoke toxicity test method and its comparison with real-scale fire tests.

A comprehensive methodology has been developed for obtaining and using smoke toxicity data for fire hazard analysis. This bench-scale method can simulate diverse fire conditions and identify extremely toxic smoke under both pre- and post-flashover conditions. However, incidence data show that most of the fire deaths in the U.S. occur outside the room of fire origin from smoke and toxic gases that are generated from a fire under post-flashover conditions. Therefore, the most relevant real-scale combustion conditions to simulate in the bench-scale apparatus would be the post-flashover conditions which are achieved by using radiant heat, a high heat flux, and correcting the bench-scale carbon monoxide (CO) results to agree with CO yields observed in real-scale post-flashover fires. The number of test animals (Fischer 344 male rats) is minimized by using the N-Gas Model to estimate the LC50 value from the chemical analysis of the smoke. The current N-Gas Model predicts the toxicity of complex fire gas mixtures based on a large data base of experimental results of individual and mixed gases that include CO, CO2, reduced O2, HCN, HCl, HBr, and NOx. The prediction is checked with a small number of animal tests and an approximate LC50 value is determined. The bench-scale results have been validated with full-scale room wall burns of a limited number of materials of widely differing characteristics chosen to challenge the system. The toxic potency values are assessed to determine if the smoke from a material or product is unusually or extremely toxic and can then be used in computations of fire hazard.

Animals↗
PubMed2001

Noradrenergic regulation of hippocampal place cells.

The influence of noradrenergic input to the hippocampus was assessed by recording hippocampal place cells and by modulating the noradrenergic tone with a selective agonist and antagonist of the alpha2-autoreceptors. The rats received intraperitoneal injection of 5 microg/kg of dexmedetomidine (DEX), an alpha2-agonist, 0.2 mg/kg of atipamezole (ATI), an alpha2-antagonist, or saline. Hippocampal place cells were recorded in a familiar rectangular environment and in three types of new environments (rectangle, square, and cylinder). Recordings in the familiar environment were conducted in two phases, either before (early phase) or after (late phase) the exposure to new environments. In the familiar environment, DEX significantly increased the mean firing rate of hippocampal interneurons, while ATI increased the mean firing rate of pyramidal cells. Only ATI in the early phase of the experiment impaired spatial selectivity. Both drugs induced field rotations in the early phase of the study, but in the late phase DEX decreased, while ATI increased field stability in the familiar environment. The drug effects in the new environment were dependent on degree of novelty. No difference between treatments was observed in the new rectangle, but in the square and cylinder, ATI increased the mean firing rate, number of fields, and field area compared to other treatments. Stability of the original firing fields in the familiar rectangle was dependent on type of interfering environment and drug treatment. Exposure to another rectangle had the smallest impact, and exposure to a square the largest impact, on the original field pattern. ATI impaired stability of the original field after exposure to a rectangular and cylinder, while the impairing effect of DEX was only observed after exposure to a cylinder. In conclusion, increased noradrenergic tone increases the firing rate of hippocampal place cells, especially when the experimental situation and environment are new, but this increase is spatially nonselective. Furthermore, manipulation of the noradrenergic tone in either direction leads to instability of firing fields.

Adrenergic alpha-Agonists↗
PubMed1991

Instability of motor unit firing rates during prolonged isometric contractions in human masseter.

The firing patterns of up to 4 concurrently active masseter motor units were studied with intramuscular electrodes during a continuous isometric contraction of 15 min duration, in which the subject maintained the mean firing rate of one selected unit at 10 Hz. With this paradigm the net excitation (i.e. mean firing rate) of one unit in the muscle was controlled. This served as the reference for the functional state of other active units during the prolonged contraction. With the mean firing rate of one unit in the muscle fixed, 58% of other active units showed a slow, statistically-significant change in mean firing rate over the 15 min. The initial firing rate of the units did not influence the change in rate. The original firing rate hierarchy, which in short-term contractions reflects the recruitment order, was altered during the prolonged contraction. The explanation for these differential changes in motoneuron net excitation is not clear; they could be intrinsic to the motoneurons or perhaps mediated by reflex pathways. The selective facilitation or suppression of some motor units with continuous activation means that the original size-structured combination of motor units can be modified during a prolonged contraction.

Adolescent↗
PubMed1999

Myelinated afferent fiber types that become spontaneously active and mechanosensitive following nerve transection in the rat.

It is difficult to know which afferent types preferentially develop ectopic firing characteristics following nerve injury because axotomy disconnects the sensory receptor ending from the remainder of the afferent neuron. We compared the prevalence of ectopic firing originating in nerve-end neuromas of nerves serving muscle and skin in the rat. Spontaneous firing was much more prevalent in the injured medial gastrocnemius nerve, a hindlimb muscle nerve, than in the saphenous and sural nerves which primarily innervate hindlimb skin. Ectopic mechanosensitivity, on the other hand, was more prominent in neuromas of the cutaneous nerves. In neuromas of the facial nerve, a cranial nerve which serves striated muscles of the face, there was no spontaneous discharge and very little ectopic mechanosensitivity. We conclude that the development of spontaneous ectopic discharge and ectopic mechanosensitivity depends on the type of myelinated afferent fiber involved.

Action Potentials↗
PubMed1975

Piribedil and apomorphine: pre- and postsynaptic effects on dopamine synthesis and neuronal activity.

Piribedil and apomorphine can cause a complete but temporary inhibition in firing of the DA-containing neurons. The cells recover to approximately 30 to 40% of the original firing rate, and with subsequent administration of the drug become more and more resistant to further inhibition. At this point they are also resistant to inhibition by other direct- or indirect-acting DA agonists that are normally able to inhibit the firing of DA cells. This effect may be due to an interaction of the DA agonists with the postsynaptic DA receptors, but apomorphine at least is able to inhibit the firing of DA cells directly when iontophoresed onto the DA cell body (Aghajanian and Bunney, 1973). These drugs can block the increase in DA synthesis observed in the absence of impulse flow, indicating a presynaptic site of acttion. Taken together, these results suggest that in interpreting the effects of drugs interacting with the DA systems several points of interaction should be considered.

Animals↗
PubMed2004

Tree growth and competition in a Betula platyphylla-Larix cajanderi post-fire forest in central Kamchatka.

BACKGROUND AND AIMS: Fire is the dominant disturbance in central Kamchatka boreal forests, yet patterns and mechanisms of stand recovery have not been investigated. METHODS: Measurements were made of 1433 stems > or =1.3 m height and annual radial increments of 225 randomly selected trees in a 0.4-ha plot of a 53-year-old fire-origin mixed-species stand to examine the spatio-temporal variation in establishment, growth, size inequality and the mode of competition among individual trees. Growth variations were related to tree size, age and local interference with neighbours. KEY RESULTS: Betula platyphylla formed the main canopy following a fire in 1947, with Larix cajanderi and Pinus pumila progressively reinvading the lower tree and shrub stratum. Most B. platyphylla originated from sprouts in small patches (polycormons) during the first 15 post-fire years. Betula platyphylla had normal distributions of diameter and age classes, but negatively skewed height distribution, as expected from shade-intolerant, pioneer species. Larix cajanderi had fewer tall and many short individuals. The smaller and younger B. platyphylla grew disproportionately more in diameter than larger trees from 1950 to 1975, and hence stem size inequalities decreased. The reverse trend was observed from 1995 to 2000: larger trees grew more, indicating an increasing asymmetry of competition for light. Betula platyphylla had steady diameter growth in the first 25 post-fire years, after which the growth declined in smaller trees. Neighbourhood analysis showed that the decline resulted from increased competition from taller neighbours. CONCLUSIONS: The observed growth patterns suggest that mode of interactions altered during stand development from early stages of weak competition for soil resources released by fire to later stages of asymmetric competition for light. Asymmetric crown competition started later than reported in other studies, which can be attributed to the lower stem density leaving much space for individual growth, greater relative importance of below-ground competition in this site of nutrient-poor volcanic soil, and the vegetative origin of B. platyphylla. Larix cajanderi growing under B. platyphylla had steady diameter growth during the first 20 years, after which growth declined. It is suggested that early succession fits the tolerance model of succession, while inhibition dominates in later stages.

Betula↗
PubMed1999

Differential assembly of Cdc45p and DNA polymerases at early and late origins of DNA replication.

Chromosomes are replicated in characteristic, temporal patterns during S phase. We have compared the timing of association of replication proteins at early- and late-replicating origins of replication. Minichromosome maintenance proteins assemble simultaneously at early- and late-replicating origins. In contrast, Cdc45p association with late origins is delayed relative to early origins. DNA polymerase alpha association is similarly delayed at late origins and requires Cdc45p function. Activation of the S phase checkpoint inhibits association of Cdc45p with late-firing origins. These studies suggest that Cdc45p is poised to serve as a key regulatory target for both the temporal and checkpoint-mediated regulation of replication origins.

Carrier Proteins↗
PubMed2000

Interaction of Xenopus Cdc2 x cyclin A1 with the origin recognition complex.

The initiation of DNA replication in eukaryotes is regulated in a minimum of at least two ways. First, several proteins, including origin recognition complex (ORC), Cdc6 protein, and the minichromosome maintenance (MCM) protein complex, need to be assembled on chromatin before initiation. Second, cyclin-dependent kinases regulate DNA replication in both a positive and a negative way by inducing the initiation of DNA replication at G(1)/S transition and preventing further rounds of origin firing within the same cell cycle. Here we characterize a link between the two levels. Immunoprecipitation of Xenopus origin recognition complex with anti-XOrc1 or anti-XOrc2 antibodies specifically co-immunoprecipitates a histone H1 kinase activity. The kinase activity is sensitive to several inhibitors of cyclin-dependent kinases including 6-dimethylaminopurine (6-DMAP), olomoucine, and p21(Cip1). This kinase activity also copurifies with ORC over several fractionation steps and was identified as a complex of the Cdc2 catalytic subunit and cyclin A1. Neither Cdk2 nor cyclin E could be detected in ORC immunoprecipitations. Reciprocal immunoprecipitations with anti-Xenopus Cdc2 or anti-Xenopus cyclin A1 antibodies specifically co-precipitate XOrc1 and XOrc2. Our results indicate that Xenopus ORC and Cdc2 x cyclin A1 physically interact and demonstrate a physical link between an active cyclin-dependent kinase and proteins involved in the initiation of DNA replication.

Adenine↗
PubMed2001

Reconstitution of licensed replication origins on Xenopus sperm nuclei using purified proteins.

BACKGROUND: In order to ensure precise chromosome duplication, eukaryotes "license" their replication origins during late mitosis and early G1 by assembling complexes of Mcm2-7 onto them. Mcm2-7 are essential for DNA replication, but are displaced from origins as they initiate, thus ensuring that no origin fires more than once in a single cell cycle. RESULTS: Here we show that a combination of purified nucleoplasmin, the origin recognition complex (ORC), Cdc6, RLF-B/Cdt1 and Mcm2-7 can promote functional origin licensing and the assembly of Mcm2-7 onto Xenopus sperm nuclei. The reconstituted reaction is inhibited by geminin, a specific RLF-B/Cdt1 inhibitor. Interestingly, the purified ORC used in the reconstitution had apparently lost the Orc6 subunit, suggesting that Orc6 is not essential for replication licensing. We use the reconstituted system to make a preliminary analysis of the different events occurring during origin assembly, and examine their nucleotide requirements. We show that the loading of Xenopus ORC onto chromatin is strongly stimulated by both ADP, ATP and ATP-gamma-S whilst the loading of Cdc6 and Cdt1 is stimulated only by ATP or ATP-gamma-S. CONCLUSIONS: Nucleoplasmin, ORC, Cdc6, RLF-B/Cdt1 and Mcm2-7 are the only proteins required for functional licensing and the loading of Mcm2-7 onto chromatin. The requirement for nucleoplasmin probably only reflects a requirement to decondense sperm chromatin before ORC can bind to it. Use of this reconstituted system should allow a full biochemical analysis of origin licensing and Mcm2-7 loading.

Animals↗
PubMed2002

Identification of Tah11/Sid2 as the ortholog of the replication licensing factor Cdt1 in Saccharomyces cerevisiae.

Faithful duplication of the genetic material requires that replication origins fire only once per cell cycle. Central to this control is the tightly regulated formation of prereplicative complexes (preRCs) at future origins of DNA replication. In all eukaryotes studied, this entails loading by Cdc6 of the Mcm2-7 helicase next to the origin recognition complex (ORC). More recently, another factor, named Cdt1, was shown to be essential for Mcm loading in fission yeast and Xenopus as well as for DNA replication in Drosophila and humans. Surprisingly, no Cdt1 homolog was found in budding yeast, despite the conserved nature of origin licensing. Here we identify Tah11/Sid2, previously isolated through interactions with topoisomerase and Cdk inhibitor mutants, as an ortholog of Cdt1. We show that sid2 mutants lose minichromosomes in an ARS number-dependent manner, consistent with ScCdt1/Sid2 being involved in origin licensing. Accordingly, cells partially depleted of Cdt1 replicate DNA from fewer origins, whereas fully depleted cells fail to load Mcm2 on chromatin and fail to initiate but not elongate DNA synthesis. We conclude that origin licensing depends in S. cerevisiae as in other eukaryotes on both Cdc6 and Cdt1.

Amino Acid Sequence↗
PubMed2002

ORC and the intra-S-phase checkpoint: a threshold regulates Rad53p activation in S phase.

The intra-S-phase checkpoint in yeast responds to stalled replication forks by activating the ATM-like kinase Mec1 and the CHK2-related kinase Rad53, which in turn inhibit spindle elongation and late origin firing and lead to a stabilization of DNA polymerases at arrested forks. A mutation that destabilizes the second subunit of the Origin Recognition Complex, orc2-1, reduces the number of functional replication forks by 30% and severely compromises the activation of Rad53 by replication stress or DNA damage in S phase. We show that the restoration of the checkpoint response correlates in a dose-dependent manner with the restoration of pre-replication complex formation in G1. Other forms of DNA damage can compensate for the reduced level of fork-dependent signal in the orc2-1 mutant, yet even in wild-type cells, the amount of damage required for Rad53 activation is higher in S phase than in G2. Our data suggest the existence of an S-phase-specific threshold that may be necessary to allow cells to tolerate damage-like DNA structures present at normal replication forks.

Cell Cycle Proteins↗
PubMed1999

Activation of dormant origins of DNA replication in budding yeast.

Eukaryotic genomes often contain more potential replication origins than are actually used during S phase. The molecular mechanisms that prevent some origins from firing are unknown. Here we show that dormant replication origins on the left arm of budding yeast chromosome III become activated when both passive replication through them is prevented and the Mec1/Rad53 checkpoint that blocks late-origin firing is inactivated. Under these conditions, dormant origins fire very late relative to other active origins. These experiments show that some dormant replication origins are competent to fire during S phase and that passage of a replication fork through such origins can inactivate them.

Cell Cycle↗
PubMed2006

Regulating the licensing of DNA replication origins in metazoa.

Eukaryotic DNA replication is a highly conserved process; the proteins and sequence of events that replicate animal genomes are remarkably similar to those that replicate yeast genomes. Moreover, the assembly of prereplication complexes at DNA replication origins ('DNA licensing') is regulated in all eukaryotes so that no origin fires more than once in a single cell cycle. And yet there are significant differences between species both in the selection of replication origins and in the way in which these origins are licensed to operate. Moreover, these differences impart advantages to multicellular animals and plants that facilitate their development, such as better control over endoreduplication, flexibility in origin selection, and discrimination between quiescent and proliferative states.

Animals↗
PubMed2006

Gradual translocation of spatial correlates of neuronal firing in the hippocampus toward prospective reward locations.

In a continuous T-maze alternation task, CA1 complex-spike neurons in the hippocampus differentially fire as the rat traverses overlapping segments of the maze (i.e., the stem) repeatedly via alternate routes. The temporal dynamics of this phenomenon were further investigated in the current study. Rats learned the alternation task from the first day of acquisition and the differential firing pattern in the stem was observed accordingly. More importantly, we report a phenomenon in which spatial correlates of CA1 neuronal ensembles gradually changed from their original firing locations, shifting toward prospective goal locations in the continuous T-maze alternation task. The relative locations of simultaneously recorded firing fields, however, were preserved within the ensemble spatial representation during this shifting. The within-session shifts in preferred firing locations in the absence of any changes in the environment suggest that certain cognitive factors can significantly alter the location-bound coding scheme of hippocampal neurons.

Animals↗
PubMed1996

An essential role for the Cdc6 protein in forming the pre-replicative complexes of budding yeast.

Origins of DNA replication in Saccharomyces cerevisiae are bound by two protein complexes during the cell cycle. Post-replicative complexes closely resemble those generated in vitro by purified origin recognition complex (ORC), which is essential for DNA replication in vivo. Pre-replicative complexes (pre-RCs) are characterized by an extended region of nuclease protection overlapping the ORC footprint. We show here that the Cdc6 protein (Cdc6p), which is necessary for origin firing in vivo, is essential for the establishment and maintenance of pre-RCs, suggesting that it is a component of these complexes. Without Cdc6p, G1 origins closely resemble post-replicative origins, providing evidence that ORC is also a component of pre-RCs. These results suggest that pre-RCs play an essential role in initiating DNA replication and support a two-step mechanism for the assembly of functional initiation complexes.

Cell Cycle Proteins↗
PubMed1994

Radiation effects on DNA synthesis in a defined chromosomal replicon.

It has recently been shown that the tumor suppressor p53 mediates a signal transduction pathway that responds to DNA damage by arresting cells in the late G1 period of the cell cycle. However, the operation of this pathway alone cannot explain the 50% reduction in the rate of DNA synthesis that occurs within 30 min of irradiation of an asynchronous cell population. We are using the amplified dihydrofolate reductase (DHFR) domain in the methotrexate-resistant CHO cell line, CHOC 400, as a model replicon in which to study this acute radiation effect. We first show that the CHOC 400 cell line retains the classical acute-phase response but does not display the late G1 arrest that characterizes the p53-mediated checkpoint. Using a two-dimensional gel replicon-mapping method, we then show that when asynchronous cultures are irradiated with 900 cGy, initiation in the DHFR locus is completely inhibited within 30 min and does not resume for 3 to 4 h. Since initiation in this locus occurs throughout the first 2 h of the S period, this result implies the existence of a p53-independent S-phase damage-sensing pathway that functions at the level of individual origins. Results obtained with the replication inhibitor mimosine define a position near the G1/S boundary beyond which cells are unable to prevent initiation at early-firing origins in response to irradiation. This is the first direct demonstration at a defined chromosomal origin that radiation quantitatively down-regulates initiation.

Animals↗
PubMed1997

The action of prostaglandin E2 and triamcinolone acetonide on the firing activity of lumbar nerve roots.

Sciatica, due to lumbar disc herniation, is understood electrophysiogically to be an ectopic firing originating from a nerve root. The recent concept of chemical radiculitis implies the involvement, not only of mechanical compression, but also of chemical mediators which contribute to the generation of ectopic firing. The present study demonstrates that prostaglandin E2, a chemical mediator of inflammation, provoked the ectopic firing of nerve roots in a canine in vitro model which indicates that it may play a part in the irritation of nerve roots. In contrast, triamcinolone acetonide suppressed the firing induced by prostaglandin suggesting that steroids may be effective in the treatment of root symptoms.

Action Potentials↗
PubMed1985

Suicidal fire deaths revisited.

A study of self-immolation or suicidal fire deaths was performed on the case files of the Office of the Medical Examiner of Metropolitan Dade County in Miami, Florida, during the 8-year period from 1977 to 1984. A total of 24 cases, representing 0.96% of the suicides that occurred during this period, were collected and analyzed as to age, race, sex cause of death of the victim along with the blood alcohol content at autopsy, drugs detected at autopsy, and the terminal carboxyhemoglobin. Additionally, the scene circumstances, geographic location of the terminal incident, the reason for the suicide, whether or not there was a past suicide attempt, a past psychiatric history, how the fire was started, presence or absence of an outside example, time of occurrence, presence of hospitalization, and presence of a suicide note were also noted. Most of the victims were white women of over 50 years of age who died of thermal injuries. Half of the time the blood alcohol content was negative at autopsy, 1/3 of the time the drug screen was negative, and 1/3 of the time a small amount of carboxyhemoglobin was noted. Most fires originated at home, although motor vehicles were also common. Reasons for the suicide were varied. Of the cases 1/3 had a precious suicide attempt and approximately 1/2 of the cases had a psychiatric history. Commonly, the fire is started by pouring a flammable liquid on one-self as isopropyl (rubbing) alcohol or gasoline and igniting it. No outside media examples were noted. These events occurred more frequently in the afternoon or evening.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗