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S Heber

Publications and source records attributed to S Heber.

14 recordsLinked to original sources
PubMed2002

Common intervals and sorting by reversals: a marriage of necessity.

This paper revisits the problem of sorting by reversals with tools developed in the context of detecting common intervals. Mixing the two approaches yields new definitions and algorithms for the reversal distance computations, that apply directly on the original permutation. Traditional constructions such as recasting the signed permutation as a positive permutation, or traversing the overlap graph to analyze its connected components, are replaced by elementary definitions in terms of intervals of the permutation. This yields simple linear time algorithms that identify the essential features in a single pass over the permutation and use only simple data structures like arrays and stacks.

Algorithms↗
PubMed2000

Mice with combined gene knock-outs reveal essential and partially redundant functions of amyloid precursor protein family members.

The amyloid precursor protein (APP) involved in Alzheimer's disease is a member of a larger gene family including amyloid precursor-like proteins APLP1 and APLP2. We generated and examined the phenotypes of mice lacking individual or all possible combinations of APP family members to assess potential functional redundancies within the gene family. Mice deficient for the nervous system-specific APLP1 protein showed a postnatal growth deficit as the only obvious abnormality. In contrast to this minor phenotype, APLP2(-/-)/APLP1(-/-) and APLP2(-/-)/APP(-/-) mice proved lethal early postnatally. Surprisingly, APLP1(-/-)/APP(-/-) mice were viable, apparently normal, and showed no compensatory upregulation of APLP2 expression. These data indicate redundancy between APLP2 and both other family members and corroborate a key physiological role for APLP2. This view gains further support by the observation that APLP1(-/-)/APP(-/-)/APLP2(+/-) mice display postnatal lethality. In addition, they provide genetic evidence for at least some distinct physiological roles of APP and APLP2 by demonstrating that combinations of single knock-outs with the APLP1 mutation resulted in double mutants of clearly different phenotypes, being either lethal, or viable. None of the lethal double mutants displayed, however, obvious histopathological abnormalities in the brain or any other organ examined. Moreover, cortical neurons from single or combined mutant mice showed unaltered survival rates under basal culture conditions and unaltered susceptibility to glutamate excitotoxicity in vitro.

Amyloid beta-Protein Precursor↗
PubMed2000

Application of bootstrap techniques to physical mapping.

Ordering genetic markers or clones from a genomic library into a physical map is a central problem in genetics. In the presence of errors, there is no efficient algorithm known that solves this problem. Based on a standard heuristic algorithm for it, we present a method to construct a confidence neighborhood for a computed solution. We compute a confidence value for putative local solutions derived from bootstrap replicates of the original solution. In the reliable parts, the confidence neighborhood and the computed solution tend to coincide. In regions that are ill-defined by the data, the neighborhood contains additional reasonable alternatives. This offers the possibility of designing further experiments for the badly defined regions to improve the quality of the physical map. We analyze our approach by a simulation study and by application to a dataset of the genome of the bacterium Xylella fastidiosa.

Algorithms↗
PubMed2000

Mapping analysis of the Xylella fastidiosa genome.

A cosmid library was made of the 2.7 Mb genome of the Gram-negative plant pathogenic bacterium Xylella fastidiosa and analysed by hybridisation mapping. Clones taken from the library as well as genomic restriction fragments of rarely cutting enzymes were used as probes. The latter served as a backbone for ordering the initial map contigs and thus facilitated gap closure. Also, the co-linearity of the cosmid map, and thus the eventual sequence, could be confirmed by this process. A subset of the eventual clone coverage was distributed to the Brazilian X.FASTIDIOSA: sequencing network. Data from this effort confirmed more quantitatively initial results from the hybridisation mapping that the redundancy of clone coverage ranged between 0 and 45-fold across the genome, while the average was 15-fold by experimental design. Reasons for this not unexpected fluctuation and the actual gaps are being discussed, as is the use of this effect for functional studies.

Brazil↗
PubMed2000

Contig selection in physical mapping.

In physical mapping, one orders a set of genetic landmarks or a library of cloned fragments of DNA according to their position in the genome. Our approach to physical mapping divides the problem into smaller and easier subproblems by partitioning the probe set into independent parts (probe contigs). For this purpose we introduce a new distance function between probes, the averaged rank distance (ARD) derived from bootstrap resampling of the raw data. The ARD measures the pairwise distances of probes within a contig and smoothes the distances of probes across different contigs. It shows distinct jumps at contig borders. This makes it appropriate for contig selection by clustering. We have designed a physical mapping algorithm that makes use of these observations and seems to be particularly well suited to the delineation of reliable contigs. We evaluated our method on data sets from two physical mapping projects. On data from the recently sequenced bacterium Xylella fastidiosa, the probe contig set produced by the new method was evaluated using the probe order derived from the sequence information. Our approach yielded a basically correct contig set. On this data we also compared our method to an approach which uses the number of supporting clones to determine contigs. Our map is much more accurate. In comparison to a physical map of Pasteurella haemolytica that was computed using simulated annealing, the newly computed map is considerably cleaner. The results of our method have already proven helpful for the design of experiments aimed at further improving the quality of a map.

Algorithms↗
PubMed1998

Optimization and automation of fluorescence-based DNA hybridization for high-throughput clone mapping.

Large-scale hybridization-based genome mapping projects, such as the production of sequence-ready physical clone maps, call for robust and cheap DNA labeling techniques that are amenable to automation. We routinely use a high-throughput protocol based on fluorescence detection. DNA probes are labeled via polymerase chain reaction (PCR) amplification with primers that are digoxigenin-modified at their 5' ends. Alternatively, digoxigenin-labeled dUTP is incorporated in a random hexamer priming reaction. Hybridization takes place in small volumes by sandwiching the probe between filters and plastic sheets. A fluorescence signal is produced by the activity of alkaline phosphatase attached to an anti-digoxigenin antibody upon the addition of AttoPhos substrate. Signals are directly detected with a charge-coupled device (CCD) camera and scored by an image data analysis system. DNA filters can be reused at least 40 times without loss of data quality. Significant advantages compared to radioactive techniques are the reduced health risk, enabling highly parallel processing; the production of spot signals uniform in size and intensity, which is essential for efficient image analysis; and a cost reduction of about 70%.

Alkaline Phosphatase↗
PubMed1991

Genetic regulation of cardiolipin synthase in Escherichia coli.

Recombinant DNA and genetic techniques were used to construct Escherichia coli strains SOH92 [phi(cls-lacZ+)] and SOH93 [phi(cls-'lacZ)hyb]. beta-Galactosidase (116 kDa) synthesized by strain SOH92 was primarily present in the particulate fraction. Strain SOH92 produced about 20-fold more beta-galactosidase activity than strain SOH93. Expression of clsphilacZ in both SOH92 and SOH93 was influenced by the terminal electron acceptor (increasing in the order oxygen, nitrate, fumarate) when the cells were cultured in minimal medium with glycerol as the sole carbon source. As strains SOH92 and SOH93 progressed from early to late log growth phase under aerobic conditions in LB broth, clsphilacZ expression increased about 2.5-fold. Fusion strains containing a pss-1 allele had an increased cardiolipin (CL) level, but no corresponding increase in clsphilacZ expression was observed. A cls::Tn10dTet null mutation was introduced into SOH92 and SOH93. The strains produced less CL, but no corresponding changes in clsphilacZ expression were observed. A high copy number plasmid bearing the cls gene had no effect on clsphilacZ expression. Taken together, these results indicate that cls is not subject to autogenous regulation.

Blotting, Southern↗
PubMed1989

Differentiating multiple personality disorder and complex partial seizures.

A number of reports have suggested that some cases of multiple personality disorder might be due to temporal lobe epileptic discharges. We have administered a structured interview, the Dissociative Disorders Interview Schedule, to 20 subjects with multiple personality disorder, 20 with complex partial seizures, and 28 neurologic controls. Subjects also completed the Dissociative Experiences Scale. Results show that multiple personality can be differentiated from complex partial seizures on a large number of items. The seizure patients did not differ from controls. The data indicate that the phenomenologies of these two disorders are distinct, and, therefore, there is little reason to assume a common etiology.

Adult↗
PubMed1989

Somatic symptoms in multiple personality disorder.

A structured interview, the Dissociative Disorders Interview Schedule, was administered to 20 patients with multiple personality disorder, 20 with panic disorder, 20 with eating disorders, and 20 with schizophrenia. The frequencies of somatization disorder and of individual somatic symptoms in the four groups were compared. The multiple-personality patients reported more somatic symptoms than the other groups. Of the 20 multiple-personality patients, seven met the criteria for somatization disorder. The average number of somatic symptoms per multiple-personality patient was 13.5.

Adult↗
PubMed1989

Differences between multiple personality disorder and other diagnostic groups on structured interview.

The Dissociative Disorders Interview Schedule was administered to 20 subjects with multiple personality disorder, 20 with schizophrenia, 20 with panic disorder, and 20 with eating disorders. The findings showed that multiple personality can be differentiated from the other groups on variables such as history of physical abuse, sexual abuse, substance abuse, sleepwalking, childhood imaginary playmates, secondary features of multiple personality and extrasensory and supernatural experiences. Those with multiple personality also differ from the other groups on DSM-III criteria for multiple personality, psychogenic amnesia, and psychogenic fugue. The groups did not differ on the number of subjects who had had a major depressive episode.

Adult↗