CiteULike: Tag landmark

Brocade: Landmark Routing on Overlay Networks

Ben Zhao — 2008-04-14T01:18:23-00:00

Vol. 2429 (2002), pp. 34-44.

An investigation of geographic mapping techniques for internet hosts

Venkata Padmanabhan — 2006-05-13T15:43:50-00:00

Vol. 31, No. 4. (October 2001), pp. 173-185.

Neural correlates of human wayfinding in stroke patients.

M van Asselen — 2006-07-02T03:26:41-00:00

Brain Res, Vol. 1067, No. 1. (5 January 2006), pp. 229-238.

Wayfinding is a complex cognitive function involving different types of information, such as knowledge about landmarks and direction information. This variety of processes suggest that multiple neural mechanisms are involved, e.g., the hippocampal system, the posterior parietal and temporal cortical areas. Although patient studies and imaging studies have given important insights in the exact neural circuitry underlying wayfinding, many controversies remain. Therefore, the current study sets out to further examine the neuroanatomical correlates of wayfinding in a sample of 31 stroke patients with unilateral lesions, tested with a series of different wayfinding tasks, including landmark recognition, landmark ordering, route reversal and route drawing. For all patients, the exact location of their lesion was determined using CT or MRI scans. Based on existing literature, a number of relevant brain areas were demarcated, after which the extent of damage to these areas was determined for each patient separately. Performance on the landmark recognition task was impaired by damage to the right hippocampal formation, whereas a weak correlation was found between damage to the dorsolateral prefrontal cortex and processing the order of the landmarks. Several brain areas were found to be involved in retracing a route from the end to the beginning, including the right hippocampal formation, the right posterior parietal cortex, the right dorsolateral prefrontal cortex and the right temporal lobe. Finally, damage to the right temporal lobe impaired the ability to draw the route.

New approaches in hominoid taxonomy: Morphometrics

Franck Guy — 2008-04-01T01:02:41-00:00

American Journal of Physical Anthropology, Vol. 121, No. 3. (2003), pp. 198-218.

We report here on new cranial data relevant to hominoid taxonomic analyses, based on a study of 438 skulls belonging to 13 nonhuman living hominoid taxa. Nineteen landmarks were selected to describe the overall shape of the maxillofacial complex, in order to investigate its discriminative power in taxonomic analyses. We used a geometric morphometrics approach to depict morphological variation from the genus down to the subspecific level, and we evaluated whether our morphologic criteria are relevant to discriminating species and subspecies among living hominoids. Considering previous genetic studies, we discuss whether our results can be extrapolated to the hominin fossil record, providing a reference for species and subspecies morphologic differentiation. Our results indicate that the relative warp method, as applied to facial landmarks, provides a powerful tool to discriminate taxa down to a subspecific level. Results show a noticeable divergence of P. t. verus compared to P. t. troglodytes and P. t. schweinfurthii. According to our data, the distance between eastern and western gorilla populations as well as between Bornean and Sumatran orangutan subspecies is as great as between the two species of Pan. In the same manner, differences between Hylobates and Symphalangus are similar to those between Pan and Gorilla genera. Congruence between the morphological distances computed in this study and previous morphological and genetical studies strongly supports their relevance for morphological species recognition in paleoanthropology. Our data provide an objective standard for assessing taxonomic differences among hominoids, and will enable us to define more precisely the significance of morphological differences in the fossil record. Am J Phys Anthropol, 2003. © 2003 Wiley-Liss, Inc.

The promise of geometric morphometrics

Joan Richtsmeier — 2008-04-01T01:41:53-00:00

American Journal of Physical Anthropology, Vol. 119, No. S35. (2002), pp. 63-91.

Nontraditional or geometric morphometric methods have found wide application in the biological sciences, especially in anthropology, a field with a strong history of measurement of biological form. Controversy has arisen over which method is the

Advances in Anthropological Morphometrics

JT Richtsmeier — 2008-04-01T01:39:58-00:00

Annual Review of Anthropology, Vol. 21, No. 1. (1992), pp. 283-305.

Natural Landmark Based Navigation

E Lazkano — 2007-04-26T14:55:26-00:00

The work described in this paper presents a goal oriented navigation system in a behavior-based manner. The main contributions are, in first place the in-depth study of local navigation strategies and, on the other hand, the use of natural landmarks, namely corridors and emergency exit panels. Eliminating the centralized control of modules the system performs the task as a result of the combination of many relatively simple and light weight behaviors that run concurrently.

Neural representation of object location and route direction: An event-related fMRI study.

Gabriele Janzen — 2007-07-30T14:54:24-00:00

Brain Res (23 June 2007)

The human brain distinguishes between landmarks placed at navigationally relevant and irrelevant locations. However, to provide a successful wayfinding mechanism not only landmarks but also the routes between them need to be stored. We examined the neural representation of a memory for route direction and a memory for relevant landmarks. Healthy human adults viewed objects along a route through a virtual maze. Event-related functional magnetic resonance imaging (fMRI) data were acquired during a subsequent subliminal priming recognition task. Prime-objects either preceded or succeeded a target-object on a preciously learned route. Our results provide evidence that the parahippocampal gyri distinguish between relevant and irrelevant landmarks whereas the inferior parietal gyrus, the anterior cingulate gyrus as well as the right caudate nucleus are involved in the coding of route direction. These data show that separated memory systems store different spatial information. A memory for navigationally relevant object information and a memory for route direction exist.

Variation of perisylvian and calcarine anatomic landmarks within stereotaxic proportional coordinates.

H Steinmetz — 2006-12-27T21:24:39-00:00

AJNR Am J Neuroradiol, Vol. 11, No. 6. (c 1990), pp. 1123-1130.

This investigation describes the variability in location of functionally important persylvian landmarks and of the calcarine sulcus within the Talairach stereotaxic grid, a system frequently used for cortical localization in functional images. Twenty healthy volunteers (40 hemispheres) had MR imaging under stereotaxic conditions. Outlines of the following structures were directly identified on sagittal 5-mm MR sections and marked on individual proportional grid overlays: inferior central sulcus, inferior precentral sulcus, inferior postcentral sulcus, anterior ascending ramus and posterior rami of the sylvian fissure, superior temporal sulcus, and calcarine sulcus. Maximal variation zones for these landmarks were defined by superimposition of the standardized individual data on a standard stereotaxic grid. The sulcal variation zones measured 1.5-2.0 cm. The findings indicate that macroanatomic individuality in the cerebral surface cannot be accounted for adequately by proportional coordinates, and that this method does not allow precise definition of anatomically based regions of interest for functional imaging. Instead, MR mapping of the individual sulcus pattern should be used to generate brain templates.

Landmark stability is a prerequisite for spatial but not discrimination learning.

R Biegler — 2006-03-05T14:26:27-00:00

Nature, Vol. 361, No. 6413. (18 February 1993), pp. 631-633.

Neurons sensitive to both place and direction from distinct regions of the hippocampal formation, allometric relationships between spatial learning and hippocampal structure and pronounced impairments in spatial learning after lesions in this area, indicate that the hippocampal formation subserves allocentric spatial learning. To learn more about the process of spatial representation, we have developed a task that provides independent control of both landmark and directional cues. On the basis of physiological and behavioural work, this task also makes it possible to investigate the relevance of associative learning principles, such as predictability, to the spatial domain. We report here that although rats learn to discriminate between landmarks on the basis of their proximity to a reliably predicted food reward, they will only learn to use them to represent its location if they maintain stable locations within a geometric frame of reference.

Competition between landmarks in spatial learning: the role of proximity to the goal.

VD Chamizo — 2006-03-05T14:53:30-00:00

Behav Processes, Vol. 71, No. 1. (10 January 2006), pp. 59-65.

In two experiments, rats were trained to find a hidden platform in a Morris pool in the presence of two landmarks. Landmark B was present on all training trials, on half the trials accompanied by landmark A, on the remainder by landmark C. For rats in Group Bn, B was near the location of the platform; for those in Group Bf, B was far from the platform. Group Bn performed better than Group Bf on test trials to B alone, but significantly worse on test trials to a new configuration formed by A and C. Thus, the spatial proximity of B to the platform affected not only how well it could be used to locate the platform, but also its ability to prevent learning about other landmarks.

Learning of landmark stability and instability by hippocampal place cells.

KJ Jeffery — 2006-03-05T14:52:16-00:00

Neuropharmacology, Vol. 37, No. 4-5. (y 1998), pp. 677-687.

Place cells in the rat hippocampus fire whenever the animal is in a particular location. In a symmetrical environment, their receptive fields (place fields) are oriented by visual cues, and if these are unavailable they are oriented by movement-generated (idiothetic) cues. The present study tested the hypothesis that the cells would learn not to 'trust' a visual cue if the rat experienced it to be unstable (Knierim et al., 1995. Place cells, head direction cells and the learning of landmark stability. J. Neurosci. 15, 1648-1659). In an otherwise symmetrical environment, a visual cue was moved with respect to the idiothetic cues, either in sight or out-of-sight of the rat. When the visual cue was moved out-of-sight of the rat, place fields were initially oriented by this cue in preference to the idiothetic cues. However, if the cue was seen by the rat to be mobile, place fields ceased following the visual cue and became oriented by the idiothetic cues instead. If the cue was not seen to be mobile until the rat had had several days of experience in the environment, then the fields continued to be oriented by the (now visibly mobile) visual cue. It thus appears that the orienting influence of a visual cue on place fields can be either strengthened or weakened relative to the idiothetic cues, depending on the experience of the rat.

Isolation of Chinese hamster ovary cell mutants requiring the continuous presence of taxol for cell division

FR Cabral — 2008-05-17T01:00:43-00:00

J. Cell Biol., Vol. 97, No. 1. (1 July 1983), pp. 22-29.

10.1083/jcb.97.1.22

Structural Salience of Landmarks for Route Directions

A Klippel — 2008-02-08T09:48:29-00:00

(2001)

This paper complements landmark research with an approach to formalize the structural salience of objects along routes. The aim is to automatically integrate salient objects---landmarks---into route directions. To this end, two directions of research are combined: the formalization of salience of objects and the conceptualization of wayfinding actions. We approach structural salience with some taxonomic considerations of point-like objects with respect to their positions along a route and ...

A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group.

PC Hébert — 2006-05-10T00:25:37-00:00

N Engl J Med, Vol. 340, No. 6. (11 February 1999), pp. 409-417.

BACKGROUND: To determine whether a restrictive strategy of red-cell transfusion and a liberal strategy produced equivalent results in critically ill patients, we compared the rates of death from all causes at 30 days and the severity of organ dysfunction. METHODS: We enrolled 838 critically ill patients with euvolemia after initial treatment who had hemoglobin concentrations of less than 9.0 g per deciliter within 72 hours after admission to the intensive care unit and randomly assigned 418 patients to a restrictive strategy of transfusion, in which red cells were transfused if the hemoglobin concentration dropped below 7.0 g per deciliter and hemoglobin concentrations were maintained at 7.0 to 9.0 g per deciliter, and 420 patients to a liberal strategy, in which transfusions were given when the hemoglobin concentration fell below 10.0 g per deciliter and hemoglobin concentrations were maintained at 10.0 to 12.0 g per deciliter. RESULTS: Overall, 30-day mortality was similar in the two groups (18.7 percent vs. 23.3 percent, P= 0.11). However, the rates were significantly lower with the restrictive transfusion strategy among patients who were less acutely ill -- those with an Acute Physiology and Chronic Health Evaluation II score of < or =20 (8.7 percent in the restrictive-strategy group and 16.1 percent in the liberal-strategy group; P=0.03) -- and among patients who were less than 55 years of age (5.7 percent and 13.0 percent, respectively; P=0.02), but not among patients with clinically significant cardiac disease (20.5 percent and 22.9 percent, respectively; P=0.69). The mortality rate during hospitalization was significantly lower in the restrictive-strategy group (22.3 percent vs. 28.1 percent, P=0.05). CONCLUSIONS: A restrictive strategy of red-cell transfusion is at least as effective as and possibly superior to a liberal transfusion strategy in critically ill patients, with the possible exception of patients with acute myocardial infarction and unstable angina.

Early goal-directed therapy in the treatment of severe sepsis and septic shock.

E Rivers — 2006-05-19T05:18:10-00:00

N Engl J Med, Vol. 345, No. 19. (8 November 2001), pp. 1368-1377.

BACKGROUND: Goal-directed therapy has been used for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with oxygen demand. The purpose of this study was to evaluate the efficacy of early goal-directed therapy before admission to the intensive care unit. METHODS: We randomly assigned patients who arrived at an urban emergency department with severe sepsis or septic shock to receive either six hours of early goal-directed therapy or standard therapy (as a control) before admission to the intensive care unit. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. In-hospital mortality (the primary efficacy outcome), end points with respect to resuscitation, and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were obtained serially for 72 hours and compared between the study groups. RESULTS: Of the 263 enrolled patients, 130 were randomly assigned to early goal-directed therapy and 133 to standard therapy; there were no significant differences between the groups with respect to base-line characteristics. In-hospital mortality was 30.5 percent in the group assigned to early goal-directed therapy, as compared with 46.5 percent in the group assigned to standard therapy (P = 0.009). During the interval from 7 to 72 hours, the patients assigned to early goal-directed therapy had a significantly higher mean (+/-SD) central venous oxygen saturation (70.4+/-10.7 percent vs. 65.3+/-11.4 percent), a lower lactate concentration (3.0+/-4.4 vs. 3.9+/-4.4 mmol per liter), a lower base deficit (2.0+/-6.6 vs. 5.1+/-6.7 mmol per liter), and a higher pH (7.40+/-0.12 vs. 7.36+/-0.12) than the patients assigned to standard therapy (P < or = 0.02 for all comparisons). During the same period, mean APACHE II scores were significantly lower, indicating less severe organ dysfunction, in the patients assigned to early goal-directed therapy than in those assigned to standard therapy (13.0+/-6.3 vs. 15.9+/-6.4, P < 0.001). CONCLUSIONS: Early goal-directed therapy provides significant benefits with respect to outcome in patients with severe sepsis and septic shock.

Electrocardiographic diagnosis of evolving acute myocardial infarction in the presence of left bundle-branch block. GUSTO-1 (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) Investigators.

EB Sgarbossa — 2005-08-22T01:29:13-00:00

N Engl J Med, Vol. 334, No. 8. (22 February 1996), pp. 481-487.

BACKGROUND. The presence of left bundle-branch block on the electrocardiogram may conceal the changes of acute myocardial infarction, which can delay both its recognition and treatment. We tested electrocardiographic criteria for the diagnosis of acute infarction in the presence of left bundle-branch block. METHODS. The base-line electrocardiograms of patients enrolled in the GUSTO-1 (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) trial who had left bundle-branch block and acute myocardial infarction confirmed by enzyme studies were blindly compared with the electrocardiograms of control patients who had chronic coronary artery disease and left bundle-branch block. The electrocardiographic criteria for the diagnosis of infarction were then tested in an independent sample of patients presenting with acute chest pain and left bundle-branch block. RESULTS. Of 26,003 North American patients, 131 (0.5 percent) with acute myocardial infarction had left bundle-branch block. The three electrocardiographic criteria with independent value in the diagnosis of acute infarction in these patients were an ST-segment elevation of 1 mm or more that was concordant with (in the same direction as) the QRS complex; ST-segment depression of 1 mm or more in lead V1, V2, or V3; and ST-segment elevation of 5 mm or more that was disconcordant with (in the opposite direction from) the QRS complex. We used these three criteria in a multivariate model to develop a scoring system (0 to 10), which allowed a highly specific diagnosis of acute myocardial infarction to be made. CONCLUSIONS. We developed and validated a clinical prediction rule based on a set of electrocardiographic criteria for the diagnosis of acute myocardial infarction in patients with chest pain and left bundle-branch block. The use of these criteria, which are based on simple ST-segment changes, may help identify patients with acute myocardial infarction, who can then receive appropriate treatment.

A comparison of rate control and rhythm control in patients with atrial fibrillation.

DG Wyse — 2006-02-26T01:42:33-00:00

N Engl J Med, Vol. 347, No. 23. (5 December 2002), pp. 1825-1833.

BACKGROUND: There are two approaches to the treatment of atrial fibrillation: one is cardioversion and treatment with antiarrhythmic drugs to maintain sinus rhythm, and the other is the use of rate-controlling drugs, allowing atrial fibrillation to persist. In both approaches, the use of anticoagulant drugs is recommended. METHODS: We conducted a randomized, multicenter comparison of these two treatment strategies in patients with atrial fibrillation and a high risk of stroke or death. The primary end point was overall mortality. RESULTS: A total of 4060 patients (mean [+/-SD] age, 69.7+/-9.0 years) were enrolled in the study; 70.8 percent had a history of hypertension, and 38.2 percent had coronary artery disease. Of the 3311 patients with echocardiograms, the left atrium was enlarged in 64.7 percent and left ventricular function was depressed in 26.0 percent. There were 356 deaths among the patients assigned to rhythm-control therapy and 310 deaths among those assigned to rate-control therapy (mortality at five years, 23.8 percent and 21.3 percent, respectively; hazard ratio, 1.15 [95 percent confidence interval, 0.99 to 1.34]; P=0.08). More patients in the rhythm-control group than in the rate-control group were hospitalized, and there were more adverse drug effects in the rhythm-control group as well. In both groups, the majority of strokes occurred after warfarin had been stopped or when the international normalized ratio was subtherapeutic. CONCLUSIONS: Management of atrial fibrillation with the rhythm-control strategy offers no survival advantage over the rate-control strategy, and there are potential advantages, such as a lower risk of adverse drug effects, with the rate-control strategy. Anticoagulation should be continued in this group of high-risk patients.

Intensive insulin therapy in the critically ill patients.

G van den Berghe — 2006-02-02T16:24:59-00:00

N Engl J Med, Vol. 345, No. 19. (8 November 2001), pp. 1359-1367.

BACKGROUND: Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known. METHODS: We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg per deciliter [4.4 and 6.1 mmol per liter]) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter [11.9 mmol per liter] and maintenance of glucose at a level between 180 and 200 mg per deciliter [10.0 and 11.1 mmol per liter]). RESULTS: At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (P<0.04, with adjustment for sequential analyses). The benefit of intensive insulin therapy was attributable to its effect on mortality among patients who remained in the intensive care unit for more than five days (20.2 percent with conventional treatment, as compared with 10.6 percent with intensive insulin therapy, P=0.005). The greatest reduction in mortality involved deaths due to multiple-organ failure with a proven septic focus. Intensive insulin therapy also reduced overall in-hospital mortality by 34 percent, bloodstream infections by 46 percent, acute renal failure requiring dialysis or hemofiltration by 41 percent, the median number of red-cell transfusions by 50 percent, and critical-illness polyneuropathy by 44 percent, and patients receiving intensive therapy were less likely to require prolonged mechanical ventilation and intensive care. CONCLUSIONS: Intensive insulin therapy to maintain blood glucose at or below 110 mg per deciliter reduces morbidity and mortality among critically ill patients in the surgical intensive care unit.

Protein composition of catalytically active human telomerase from immortal cells.

SB Cohen — 2007-04-03T00:24:51-00:00

Science, Vol. 315, No. 5820. (30 March 2007), pp. 1850-1853.

Telomerase is a ribonucleoprotein enzyme complex that adds 5'-TTAGGG-3' repeats onto the ends of human chromosomes, providing a telomere maintenance mechanism for approximately 90% of human cancers. We have purified human telomerase approximately 10(8)-fold, with the final elution dependent on the enzyme's ability to catalyze nucleotide addition onto a DNA oligonucleotide of telomeric sequence, thereby providing specificity for catalytically active telomerase. Mass spectrometric sequencing of the protein components and molecular size determination indicated an enzyme composition of two molecules each of telomerase reverse transcriptase, telomerase RNA, and dyskerin.

A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes.

RK Moyzis — 2006-12-01T14:27:27-00:00

Proc Natl Acad Sci U S A, Vol. 85, No. 18. (September 1988), pp. 6622-6626.

A highly conserved repetitive DNA sequence, (TTAGGG)n, has been isolated from a human recombinant repetitive DNA library. Quantitative hybridization to chromosomes sorted by flow cytometry indicates that comparable amounts of this sequence are present on each human chromosome. Both fluorescent in situ hybridization and BAL-31 nuclease digestion experiments reveal major clusters of this sequence at the telomeres of all human chromosomes. The evolutionary conservation of this DNA sequence, its terminal chromosomal location in a variety of higher eukaryotes (regardless of chromosome number or chromosome length), and its similarity to functional telomeres isolated from lower eukaryotes suggest that this sequence is a functional human telomere.

Identification of a specific telomere terminal transferase activity in Tetrahymena extracts.

CW Greider — 2007-03-31T21:54:20-00:00

Cell, Vol. 43, No. 2 Pt 1. (December 1985), pp. 405-413.

We have found a novel activity in Tetrahymena cell free extracts that adds tandem TTGGGG repeats onto synthetic telomere primers. The single-stranded DNA oligonucleotides (TTGGGG)4 and TGTGTGGGTGTGTGGGTGTGTGGG, consisting of the Tetrahymena and yeast telomeric sequences respectively, each functioned as primers for elongation, while (CCCCAA)4 and two nontelomeric sequence DNA oligomers did not. Efficient synthesis of the TTGGGG repeats depended only on addition of micromolar concentrations of oligomer primer, dGTP, and dTTP to the extract. The activity was sensitive to heat and proteinase K treatment. The repeat addition was independent of both endogenous Tetrahymena DNA and the endogenous alpha-type DNA polymerase; and a greater elongation activity was present during macronuclear development, when a large number of telomeres are formed and replicated, than during vegetative cell growth. We propose that the novel telomere terminal transferase is involved in the addition of telomeric repeats necessary for the replication of chromosome ends in eukaryotes.

Telomeres shorten during ageing of human fibroblasts.

CB Harley — 2006-12-01T14:44:00-00:00

Nature, Vol. 345, No. 6274. (31 May 1990), pp. 458-460.

The terminus of a DNA helix has been called its Achilles' heel. Thus to prevent possible incomplete replication and instability of the termini of linear DNA, eukaryotic chromosomes end in characteristic repetitive DNA sequences within specialized structures called telomeres. In immortal cells, loss of telomeric DNA due to degradation or incomplete replication is apparently balanced by telomere elongation, which may involve de novo synthesis of additional repeats by novel DNA polymerase called telomerase. Such a polymerase has been recently detected in HeLa cells. It has been proposed that the finite doubling capacity of normal mammalian cells is due to a loss of telomeric DNA and eventual deletion of essential sequences. In yeast, the est1 mutation causes gradual loss of telomeric DNA and eventual cell death mimicking senescence in higher eukaryotic cells. Here, we show that the amount and length of telomeric DNA in human fibroblasts does in fact decrease as a function of serial passage during ageing in vitro and possibly in vivo. It is not known whether this loss of DNA has a causal role in senescence.

DNA sequences of telomeres maintained in yeast.

J Shampay — 2007-03-24T23:03:30-00:00

Nature, Vol. 310, No. 5973. (8 1984), pp. 154-157.

Telomeres, the ends of eukaryotic chromosomes, have long been recognized as specialized structures. Their stability compared with broken ends of chromosomes suggested that they have properties which protect them from fusion, degradation or recombination. Furthermore, a linear DNA molecule such as that of a eukaryotic chromosome must have a structure at its ends which allows its complete replication, as no known DNA polymerase can initiate synthesis without a primer. At the ends of the relatively short, multi-copy linear DNA molecules found naturally in the nuclei of several lower eukaryotes, there are simple tandemly repeated sequences with, in the cases analysed, a specific array of single-strand breaks, on both DNA strands, in the distal portion of the block of repeats. In general, however, direct analysis of chromosomal termini presents problems because of their very low abundance in nuclei. To circumvent this problem, we have previously cloned a chromosomal telomere of the yeast Saccharomyces cerevisiae on a linear DNA vector molecule. Here we show that yeast chromosomal telomeres terminate in a DNA sequence consisting of tandem irregular repeats of the general form C1-3A. The same repeat units are added to the ends of Tetrahymena telomeres, in an apparently non-template-directed manner, during their replication on linear plasmids in yeast. Such DNA addition may have a fundamental role in telomere replication.

A theory of marginotomy : The incomplete copying of template margin in enzymic synthesis of polynucleotides and biological significance of the phenomenon

AM Olovnikov — 2007-03-24T20:05:28-00:00

Journal of Theoretical Biology, Vol. 41, No. 1. (14 September 1973), pp. 181-190.

A theory of marginotomy has been proposed to explain the limitation of the cell doubling potential of clones of normal somatic cells. Marginotomy of DNA is the shortening of the replica with respect to the template. Two possible mechanisms of marginotomy are discussed. The first mechanism is a DNA-polymerase, postulated to have a catalytically inactive zone lying between the catalytic centre and the outer edge of the enzyme molecule. The terminal template segment which is equal to the length of the non-catalytic marginal zone of the DNA-polymerase will not appear in the replica. The second mechanism of marginotomy results from a requirement for an initiating RNA-primer for activity of some DNA-polymerases. In this case the final DNA replica will be shorter than the template by the length of RNA-primer. Marginotomy causes the appearance, in the daughters of dividing cells, of more and more shortened end-genes, the so-called telogenes, with every new mitosis. The telogenes function as the starting points of end-replicons in chromosomes and also as "buffers", being sacrificed during successive mitoses. After the exhaustion of telogenes the cells become aged and are eliminated due to the loss of some vitally important genes localized in end-replicons. Marginotomy is therefore responsible for the loss with age of various cell clones of the body, including some endocrine cell clones. Therefore marginotomy may be the primary cause of various disorders of age of the ageing of multicellular organisms.

The Behavior in Successive Nuclear Divisions of a Chromosome Broken at Meiosis.

B McClintock — 2007-03-29T16:57:43-00:00

Proc Natl Acad Sci U S A, Vol. 25, No. 8. (August 1939), pp. 405-416.

A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena.

EH Blackburn — 2007-03-24T21:59:48-00:00

J Mol Biol, Vol. 120, No. 1. (25 March 1978), pp. 33-53.

Telomerase catalytic subunit homologs from fission yeast and human.

TM Nakamura — 2006-12-05T10:02:29-00:00

Science, Vol. 277, No. 5328. (15 August 1997), pp. 955-959.

Catalytic protein subunits of telomerase from the ciliate Euplotes aediculatus and the yeast Saccharomyces cerevisiae contain reverse transcriptase motifs. Here the homologous genes from the fission yeast Schizosaccharomyces pombe and human are identified. Disruption of the S. pombe gene resulted in telomere shortening and senescence, and expression of mRNA from the human gene correlated with telomerase activity in cell lines. Sequence comparisons placed the telomerase proteins in the reverse transcriptase family but revealed hallmarks that distinguish them from retroviral and retrotransposon relatives. Thus, the proposed telomerase catalytic subunits are phylogenetically conserved and represent a deep branch in the evolution of reverse transcriptases.