Temporal Order Of Events Research Articles

Brain injury: prolonged induction of transcription factors

A specific temporal order of events at the cellular and molecular level occurs in response to injury to the brain. Injury-compromised neurons degenerate while surviving neurons undergo neuritogenesis and synaptogenesis to establish neuronal connectivity destroyed in the injury. Several genes, such as those coding cytoskeletal proteins and growth factors, have been shown to be regulated by AP-1 and NF-kappaB transcription factors, two of the most studied DNA binding regulatory proteins. Our laboratory has discovered that Fos-related antigen-2 from AP-1 transcription factor family and NF-kappaB p65 and p50 subunits are induced long-term (days to months) in the brain after neurotoxic, excitotoxic or ischemic insult. Fos-related antigen-2 is induced in neurons in several models of injury and its elevated expression lasts days to months, corresponding to the severity. The time-course of FRA-2 induction is abbreviated with less severe insult (terminal damage) relative to the cell death, but the induction occurs during the period of regeneration and repair in both models. NF-kappaB p65 is basally expressed in hippocampal and cortical neurons, but is elevated in reactive astrocytes in hippocampus and entorhinal cortex starting at two days and lasting at least two weeks after kainate treatment. Neurons of the hippocampus surviving ischemic or neurotoxic injury increase expression of NF-kappaB p50 for at least a week after injury, suggesting a function for p50 in neuronal survival and/or repair. The extended expression of these transcription factors implies a role in the activation of genes related to repair and regeneration, such as growth factors and synaptic proteins, after injury to the CNS.

What are the spermatocyte's requirements for successful meiotic division?

The consequences of error during meiotic division in spermatogenesis can be serious: aneuploid spermatozoa, embryonic lethality, and developmental abnormalities. Recombination between homologs is essential to ensure normal segregation; thus the spermatocyte must time division precisely so that it occurs after recombination between chromosomes and accumulation of the cell-cycle machinery necessary to ensure an accurate segregation of chromosomes. We use two systems to investigate meiotic division during spermatogenesis in the mouse: pharmacological induction of meiotic metaphase in cultured spermatocytes and transillumination-mediated dissection of stage XII seminiferous tubule segments to monitor progress through the division phase. By these approaches we can assess timing of acquisition of competence for the meiotic division phase and the temporal order of events as division proceeds. Competence for the meiotic division arises in the mid-pachytene stage of meiotic prophase, after chromosomes have synapsed and coincident with the accumulation of the cell-cycle regulatory protein CDC25C. The activity of both MPF and topoisomerase II are required. The earliest hallmarks of the division phase are nuclear envelope breakdown, followed by phosphorylation of histone H3 and chromosome condensation. These events are likely to be monitored by checkpoint mechanisms since checkpoint proteins can be localized in nuclei and DNA-damaging agents delay entry into the meiotic division phase. Understanding how the spermatocyte regulates its entry into the meiotic division phase can help clarify the natural mechanisms ensuring accurate chromosome segregation and preventing aneuploidy. J. Exp. Zool. (Mol. Dev. Evol.) 285:243-250, 1999.

Extending CLIPS to support temporal representation and reasoning

Applications using expert systems for monitoring and control problems often require the ability to represent temporal knowledge and to apply reasoning based on that knowledge. Incorporating temporal representation and reasoning into expert systems leads to two problems in development: dealing with an implied temporal order of events using a non‐procedural tool; and maintaining the large number of temporal relations that can occur among facts in the knowledge base. In this paper we explore these problems by using an expert system shell, CLIPS (C Language Integrated Production System), to create temporal relations using common knowledge‐based constructs. We also build an extension to CLIPS through a user‐defined function which generates the temporal relations from those facts. We use the extension to create and maintain temporal relations in a workflow application that monitors and controls an engineering design change review process. We also propose a solution to ensure truth maintenance among temporally related facts that links our temporal extension to the CLIPS facility for truth maintenance.

When the Event is More Than the Sum of its Parts: 9-month-olds' Long-term Ordered Recall

Research suggests that 9-month-old infants are able to recall single object-specific actions over delays of 24 hours. In the present research we investigated whether 9-month-olds are able to recall over more extended delays, and to recall the temporal order of events, as well as the individual actions in them. In addition, we investigated whether recall can be enhanced by pre-and/or re-exposure to target events. Using elicited imitation of novel, multi-step event sequences, we demonstrated that, as a group, 9-month-olds are able to recall target actions after delays of five weeks. However, after this long delay, only 45% of the infants recalled the temporal order of the events. Re-exposure to events during the delay interval proved necessary for boys, but not for girls; pre-exposure to events did not affect later recall. The implications of individual differences in infants' recall ability for the understanding of the development of the neural correlates of declarative memory are discussed.

When temporal terms belie conceptual order.

We conceive of time as a sequential order of real-world events, one event following another from past to present to future. This conception colours the way we speak of time ("we look forward to the time") and, as we show here, the way we process written statements referring to the temporal order of events, in real time. Terms such as 'before' and 'after' give us the linguistic freedom to express a series of events (real or imaginary) in any order. However, sentences that present events out of chronological order require additional discourse-level computation. Here we examine how and when these computations are carried out by contrasting brain potentials across two sentence types that differ only in their initial word ('After' X, Y versus 'Before' X, Y). At sites on the left frontal scalp, the responses to 'before' and 'after' sentences diverge within 300 ms; the size of this difference increases over the course of the sentences and is correlated with individual working-memory spans. Thus, we show that there are immediate and lasting consequences for neural processing of the discourse implications of a single word on sentence comprehension.

The bloodstream differentiation–division ofTrypanosoma bruceistudied using mitochondrial markers

In the bloodstream of its mammalian host, the African trypanosome Trypanosoma brucei undergoes a life cycle stage differentiation from a long, slender form to a short, stumpy form. This involves three known major events: exit from a proliferative cell cycle, morphological change and mitochondrial biogenesis. Previously, models have been proposed accounting for these events (Matthews & Gull 1994a). Refinement of, and discrimination between, these models has been hindered by a lack of stage-regulated antigens useful as markers at the single-cell level. We have now evaluated a variety of cytological markers and applied them to investigate the coordination of phenotypic differentiation and cell cycle arrest. Our studies have focused on the differential expression of the mitochondrial enzyme dihydrolipoamide dehydrogenase relative to the differentiation-division of bloodstream trypanosomes. The results implicate a temporal order of events: commitment, division, phenotypic differentiation.

Fatal familial insomnia: behavioral and cognitive features.

Fatal familial insomnia (FFI) is a familial prion disease linked to a mutation of the prion protein gene. Neuropsychological investigations in seven patients with FFI belonging to two different families showed that the main behavioral and neuropsychological features are (1) early impairment of attention and vigilance, (2) memory deficits, mainly of the working memory, (3) impairment of temporal ordering of events, and (4) a progressive dream-like state with neuropsychological and behavioral features of a confusional state. Neuropathologic examination of six patients showed prominent neuronal loss and gliosis involving the anterior ventral and mediodorsal thalamic nuclei, with additional cerebral cortical involvement in two cases. Clinicopathologic correlations indicate that FFI is associated with a neuropsychological and behavioral syndrome that is distinct from the cortical and subcortical dementias, and Wernicke-Korsakoff syndrome. These findings offer insights into the function of the thalamic nuclei and challenge the notion of thalamic dementia.

Effects of the spatial and temporal ordering of events on the behaviour of a simple cellular automaton

Using a simple cellular automaton model, I demonstrate that the timing mechanism for events on different sites within the model can have a large impact on macroscopic model predictions. This implies that modellers must consider how to iterate their models so as to produce timing of events which match the biology of the problem rather than allowing a potentially unbiological timing (and hence an unrealistic model) to be imposed unintentionally by computational expedience. I discuss how to achieve this and suggest that model presentation should always describe the timing mechanism fully in order to allow others to repeat published simulation experiments.

Epithelium-mesenchyme transition during neural crest development.

The neural crest is the organ system whose presence defines vertebrates. The onset of migration of neural crest cells is an archetypal epithelium to mesenchyme transition (EMT), and this event identifies the cell lineage. Little is known yet of the establishment of the neural crest, although the zinc finger gene Slug seems to be involved in specifying EMT competence. The details, especially the temporal order of events in neural crest EMT, vary between different species and between different axial levels, but several important features have emerged from observations in situ and experiments in vitro and in vivo. EMT seems to be strongly associated with decrease in cell-cell adhesion, and particularly with loss of N-cadherin on the surface of neural crest cells at the time of onset of migration. The related adhesion molecule T-cadherin is also present, but correlated changes have not yet been described, while the unrelated adhesion molecule N-CAM also declines on neural crest cells, but with a time course unrelated to EMT. The extracellular matrix is also important: EMT-related changes in matrix receptor (i.e. integrin) activity are recorded in avian crest cells, while the nature of the matrix itself changes in urodele amphibians. Changes in cell shape and in cell motility also occur at the time of EMT, consistent with changes in the cytoskeleton. These concerted changes can be triggered by TGF-beta family growth factors, of which dorsalin-I appears particularly important. These may act through pathways involving controlled alterations in phosphorylation to effect the complex of responses that make up EMT. Although much remains to be understood, the spatiotemporal definability of this system makes it a very useful model for studying EMTs in general.

Stressful life events and changes in substance use among a multiracial/ethnic sample of adolescent boys

This paper presents a comparative analysis of the prevalence of stressful life events and of the relationships between stressful life events and alcohol, illicit drug, and cigarette use among a multi-ethnic community sample (N = 2,446) of early adolescent boys. The data were derived from a longitudinal study of substance use behaviors and their psychosocial correlates among Hispanic, African-American, and White non-Hispanic adolescent boys residing in Dade County, Florida. Similar levels of event exposure were found among the subgroups, with one exception. African Americans were significantly more likely to experience a death-related event in the past year. Stressful life events were not significantly related with substance use among African-American students. Among Hispanics and White non-Hispanics, however, a number of significant positive relationships were found. A number of bidirectional events (i.e., those events that could be either an antecedent to and/or the result of substance use) were significantly related with stressful events, highlighting the importance of longitudinal research in delineating the temporal ordering of events and outcomes. The authors conclude that future stress research with adolescents should pay particular attention to the important moderating influences of culture and ethnicity as well as to the bidirectional nature of life events and substance use.

Nonhomologous RNA recombination in tombusviruses: generation and evolution of defective interfering RNAs by stepwise deletions

We used a protoplast system to study the mechanisms involved in the generation and evolution of defective interfering (DI) RNAs of tomato bushy stunt tombusvirus (TBSV). Synthetic transcripts corresponding to different naturally occurring TBSV DI RNAs, or to various artificially constructed TBSV defective RNAs, were analyzed. The relative levels of competitiveness of different DI RNAs were determined by coinoculating their corresponding transcripts into protoplasts along with helper genomic RNA transcripts and monitoring the level of DI RNA accumulation. Further studies were performed to assess the contribution of naked DI RNA stability and DI RNA encapsidation efficiency to the observed levels of competitiveness. In addition, the ability of various defective RNAs to evolve to alternative forms was tested by serially passaging protoplast infections initiated with transcripts corresponding to helper genomic RNA and a single type of defective RNA. These studies, and the analysis of the sequences of observed recombinants, indicate that (i) replication competence is a major factor dictating DI RNA competitiveness and is likely a primary determinant in DI RNA evolution, (ii) DI RNAs are capable of evolving to both smaller and larger forms, and the rates at which various transitions occur differ, (iii) DI RNA-DI RNA recombination and/or rearrangement is responsible for the formation of the evolved RNA molecules which were examined, and (iv) sequence complementarities between positive- and negative-sense strands in the regions of the junctions suggest that, in some cases, base pairing between an incomplete replicase-associated nascent strand and acceptor template may mediate selection of recombination sites. On the basis of our data, we propose a stepwise deletion model to describe the temporal order of events leading to the formation of tombusvirus DI RNAs.

Short-term memory for the temporal order of events in monkeys

Two monkeys (Macaca fascicularis) demonstrated short-term memory for the recency of unpredictable visual events in a probe recognition task. On each trial, from two to five 3-dimensional objects were randomly selected from a pool of 200 and presented sequentially. In the test probe that followed, the subjects saw two objects from the preceding list and chose the one that had appeared earlier. Overall accuracy was 73% correct. Like human judgments of recency, accuracy varied inversely with the lag and directly with the temporal separation of the objects in the probe. The data suggest that monkeys encode information about object order as well as object identity, their mnemonic representation of the ordered list contains information about all of its constituent elements, and recency judgments are made at the time the probe is presented and not before. Monkey processing of temporal order information is in these respects similar to human order memory.

Memory for the temporal order of events in patients with frontal lobe lesions and amnesic patients

Patients with frontal lobe lesions, amnesic patients with Korsakoff's syndrome, other (non-Korsakoff) amnesic patients, and control subjects were given tests of memory for temporal order. In the first experiment, subjects were presented with a list of 15 words and then asked to reproduce the list order from a random array of the words. In the second experiment, they were asked to arrange in chronological order a random display of 15 factual events that occurred between 1941 and 1985. In both experiments, patients with frontal lobe lesions were impaired in placing the items in the correct temporal order, despite normal item memory (i.e. normal recall and recognition memory for the words and facts). The two groups of amnesic patients exhibited impaired memory for temporal order as well as impaired item memory. Patients with Korsakoff's syndrome exhibited poorer temporal order memory than the other amnesic patients, despite similar levels of item memory. These findings demonstrate that patients with frontal lobe lesions have difficulty organizing information temporally. Patients with Korsakoff's syndrome, who have both diencephalic and frontal damage, have memory impairment together with a disproportionate deficit in memory for temporal order.

SEDOS: designing open distributed systems

The aim of the ESPRIT SEDOS (software environment for the design of open systems) project is to further develop Estelle, the extended state-transition language, and LOTOS, the language for temporal ordering specifications, to describe services and protocols for distributed architectures and to demonstrate their effectiveness as concretely as possible by deriving simulators and other support tools. The Estelle language is based on extended state machines that communicate through infinite FIFO links. The LOTOS language is based on a temporal ordering of events and rendezvous.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>

The reversed eyewitness suggestibility effect

The standard temporal order of events used in studies of eyewitness suggestibility was reversed: Misled subjects were given verbal suggestions about a visual scene before witnessing it. As in the standard procedure, the subjects were later tested on memory of the visual scene. A suggestibility effect was obtained with this reversed procedure, even though the verbal information could not “update” the target memory because no memory of the visual scene existed when the misleading suggestions were given.

The effects of spatial frequency and temporal waveform on three measures of temporal processing.

The effects of spatial frequency and temporal transition of sine-wave grating onset and offset were assessed using measures of reaction time, visual persistence, and temporal order judgements. The stimuli were lateralized fields, separated by 1 degree of visual angle. Slow temporal transition resulted in significantly poorer performance than did abrupt onset and offset, but spatial frequency had a minimal effect. Thus, the latency, temporal resolution, and temporal ordering of events are mediated by a mechanism that is sensitive to abrupt temporal transients. The stimulus conditions employed did not result in a shift in the point of subjective simultaneity.

Children's Understanding of a Televised Narrative

Children at three age levels (5-6, 8-9, and 10-12 years) were exposed to a story in one of three videotape formats (audiovisual, video only, or audio only). Comprehension of the story and memory for the temporal order of events were assessed. The 5- to 6-year-olds in the video-only condition performed more poorly on the comprehension questions and tended to remember temporal order (as assessed by a picture-ordering task) less well than did subjects in all the other groups. The data suggest that understanding and integrating temporal aspects of a narrative are more difficult for young children when the story is presented visually than when it is presented verbally, whereas older children comprehend narratives in both formats equally well. This pattern of results is consistent with research indicating a greater developmental increase in the ability to analyze and interpret pictorial information than in the ability to process verbal information, at least among children in the age range studied. Unique characteristics of the way different media convey information are considered, and apparent discrepancies between the present study and previous research are discussed.

The relativity of timelike and spacelike particles from first principles

The Lorentz transformations (LT) of timelike motion are derived from first principles of geometry and the aberration phenomenon is shown to be inherent in the geometry. An extension of this procedure leads to the main features of spacelike motion. The LT for tachyons are derived and the moving observer in this LT is determined. The LTs for both timelike and spacelike motions are derived by a single method—perhaps the simplest approach to the LT. The temporal order of events and causality in tachyon motion are discussed, and the inhomogeneous wave equation for the electromagnetic potentials of a charged tachyon is solved by the use of integral transforms.

Control of timing of cell cycle events in fission yeast by the wee 1+ gene.

The means by which cells control the timing of events in the cell division cycle have been investigated in depth recently. The existence of controls over the major events of DNA replication and mitosis has been demonstrated in several systems; controls of both events have been identified in the yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe. The control points have been defined on the basis of cell cycle arrest caused by certain mutations1–4 or mating pheromones5, and by growth-related parameters3,6–10. Investigation of how the component processes, generally identified by specific genes, are organized into developmental pathways11,12 has provided much information on how the proper temporal order of events is maintained, but little is known about the control of the absolute timing of the component processes in the cycle. The time of completion of a gene-controlled process in the cell cycle can be estimated from the transition or execution point of a temperature-sensitive mutant defective in the particular gene13. In the fission yeast S. pombe the transition points of most mutants defective for mitosis are temporally clustered shortly before the event14, but the mechanism which maintains this coordination has not been investigated. I report here that the transition points of three genes required for mitosis are advanced in strains carrying a wee 1 mutation, whose best known effect is to reduce cell size at mitosis15. The observed advancement can be as much as 0.4 of the cycle, implicating the wee 1+ gene in a system which controls the timing and temporal coordination of developmental steps controlled by three mitotic genes.

Aphasic adults' understanding of complex adverbial sentences

Twelve aphasics with relatively preserved auditory comprehension were tested for their understanding of four adverbial sentence types expressing the temporal order of events. The relative effects of order of mention, adverbial choice, and adverbial clause placement on subjects' comprehension were investigated. Only adverbial choice was significant with aphasics producing more errors of temporal order on after than before sentences. Subjects' error patterns were not similar to those of children acquiring language. The results are discussed with respect to the theory of lexical marking and the regression hypothesis.