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M Lampl

Publications and source records attributed to M Lampl.

At least 19 recordsLinked to original sources
PubMed2000

A novel cold-sensitive allele of the rate-limiting enzyme of fatty acid synthesis, acetyl coenzyme A carboxylase, affects the morphology of the yeast vacuole through acylation of Vac8p.

The yeast vacuole functions both as a degradative organelle and as a storage depot for small molecules and ions. Vacuoles are dynamic reticular structures that appear to alternately fuse and fragment as a function of growth stage and environment. Vac8p, an armadillo repeat-containing protein, has previously been shown to function both in vacuolar inheritance and in protein targeting from the cytoplasm to the vacuole. Both myristoylation and palmitoylation of Vac8p are required for its efficient localization to the vacuolar membrane (Y.-X. Wang, N. L. Catlett, and L. S. Weisman, J. Cell Biol. 140:1063-1074, 1998). We report that mutants with conditional defects in the rate-limiting enzyme of fatty acid synthesis, acetyl coenzyme A carboxylase (ACC1), display unusually multilobed vacuoles, similar to those observed in vac8 mutant cells. This vacuolar phenotype of acc1 mutant cells was shown biochemically to be accompanied by a reduced acylation of Vac8p which was alleviated by fatty acid supplementation. Consistent with the proposed defect of acc1 mutant cells in acylation of Vac8p, vacuolar membrane localization of Vac8p was impaired upon shifting acc1 mutant cells to nonpermissive condition. The function of Vac8p in protein targeting, on the other hand, was not affected under these conditions. These observations link fatty acid synthesis and availability to direct morphological alterations of an organellar membrane.

Acetyl-CoA Carboxylase↗
PubMed1999

Electrospray ionization tandem mass spectrometry (ESI-MS/MS) analysis of the lipid molecular species composition of yeast subcellular membranes reveals acyl chain-based sorting/remodeling of distinct molecular species en route to the plasma membrane.

Nano-electrospray ionization tandem mass spectrometry (nano-ESI-MS/MS) was employed to determine qualitative differences in the lipid molecular species composition of a comprehensive set of organellar membranes, isolated from a single culture of Saccharomyces cerevisiae cells. Remarkable differences in the acyl chain composition of biosynthetically related phospholipid classes were observed. Acyl chain saturation was lowest in phosphatidylcholine (15.4%) and phosphatidylethanolamine (PE; 16.2%), followed by phosphatidylserine (PS; 29.4%), and highest in phosphatidylinositol (53.1%). The lipid molecular species profiles of the various membranes were generally similar, with a deviation from a calculated average profile of approximately +/- 20%. Nevertheless, clear distinctions between the molecular species profiles of different membranes were observed, suggesting that lipid sorting mechanisms are operating at the level of individual molecular species to maintain the specific lipid composition of a given membrane. Most notably, the plasma membrane is enriched in saturated species of PS and PE. The nature of the sorting mechanism that determines the lipid composition of the plasma membrane was investigated further. The accumulation of monounsaturated species of PS at the expense of diunsaturated species in the plasma membrane of wild-type cells was reversed in elo3Delta mutant cells, which synthesize C24 fatty acid-substituted sphingolipids instead of the normal C26 fatty acid-substituted species. This observation suggests that acyl chain-based sorting and/or remodeling mechanisms are operating to maintain the specific lipid molecular species composition of the yeast plasma membrane.

Acetyltransferases↗
PubMed1999

The Saccharomyces cerevisiae hyperrecombination mutant hpr1Delta is synthetically lethal with two conditional alleles of the acetyl coenzyme A carboxylase gene and causes a defect in nuclear export of polyadenylated RNA.

In a screen for mutants that display synthetic lethal interaction with hpr1Delta, a hyperrecombination mutant of Saccharomyces cerevisiae, we have isolated a novel cold-sensitive allele of the acetyl coenzyme A (CoA) carboxylase gene, acc1(cs), encoding the rate-limiting enzyme of fatty acid synthesis. The synthetic lethal phenotype of the acc1(cs) hpr1Delta double mutant was only partially complemented by exogenous fatty acids. hpr1Delta was also synthetically lethal with a previously isolated, temperature-sensitive allele of ACC1, mtr7 (mRNA transport), indicating that the lethality of the acc1(cs) hpr1Delta double mutant was not allele specific. The basis for the interaction between conditional acc1 alleles and hpr1Delta was investigated in more detail. In the hpr1Delta mutant background, acetyl-CoA carboxylase enzyme activity was reduced about 15-fold and steady-state levels of biotinylated Acc1p and ACC1 mRNA were reduced 2-fold. The reduced Acc1p activity in hpr1Delta cells, however, did not result in an altered lipid or fatty acid composition of the mutant membranes but rendered cells hypersensitive to soraphen A, an inhibitor of Acc1p. Similar to mtr7, hpr1Delta and acc1(cs) mutant cells displayed a defect in nuclear export of polyadenylated RNA. Oversized transcripts were detected in hpr1Delta, and rRNA processing was disturbed, but pre-mRNA splicing appeared wild type. Surprisingly, the transport defect of hpr1Delta and acc1(cs) mutant cells was accompanied by an altered ring-shaped structure of the nucleolus. These observations suggest that the basis for the synthetic lethal interaction between hpr1Delta and acc1 may lie in a functional overlap of the two mutations in nuclear poly(A)+ RNA production and export that results in an altered structure of the nucleolus.

Acetyl-CoA Carboxylase↗
PubMed1996

Problems in the aging of skeletal juveniles: perspectives from maturation assessments of living children.

We employ samples of children of known chronological age to demonstrate the significance of random and systematic effects on maturation in both dental and skeletal development. Differences between chronological age for dental age in young healthy Canadian children can be as much as 100% of the actual age of the children. For skeletal development by reference to Greulich-Pyle standards, three samples of known-age children from Mexico document parallel effects: 1) 183 six-year-old children have skeletal-based ages with a 95% confidence interval of 4-8 years; 2) 80% of 217 4.0-4.5-year-old children are underaged by 1-3 years; and 3) 130 children of skeletal age between 39 and 44 months are actually between 4 and 7.4 chronological years of age. The Mexican samples are drawn from a population living under conditions of environmental stress with chronic mild to moderate protein-energy malnutrition and moderate to high levels of infectious disease. These children may parallel those from the past, whose remains are studied by skeletal biologists or paleoanthropologists. Our findings reinforce concerns expressed in extant studies regarding the accuracy of age-at-death reconstructions.

Age Determination by Skeleton↗
PubMed1996

Is growth saltatory? The usefulness and limitations of frequency distributions in analyzing pulsatile data.

Several investigators have proposed that descriptive statistics can be employed to identify and discriminate growth patterns. These studies assumed that the shape of the frequency distribution of daily growth velocities (FDGVs) is diagnostic in differentiating between a pattern of growth characterized by smooth, continuous daily acquisition and a pattern of growth characterized by a discontinuous, i.e. pulsatile process. The FDGV from a saltation and stasis, i.e. episodic or pulsatile, growth pattern was assumed to be bimodal or significantly skewed to the right, whereas a continuous growth function was assumed to be approximately Gaussian. The use of FDGV characteristics is an unprecedented approach to the analysis of longitudinal growth data and was not previously validated for this use. The present study investigates the performance characteristics of the FDGV method by Monte-Carlo simulations of known saltatory, i.e. pulsatile, growth patterns. These analyses show that the FDGV for a saltation and stasis growth process can be either unimodal or bimodal and either skewed to the right or to the left. Data collection frequency, measurement error, and total study duration all determine the shape of the FDGV and the statistical significance of the results. If the FDGV is highly skewed, then it is consistent with saltatory growth. However, if the FDGV is not highly skewed, then it is consistent with both the saltatory model and a smooth, continuous growth model, and thus, the results are ambiguous. We conclude that FDGV analysis is not a valid method to exclude saltation and stasis growth processes in longitudinal growth studies.

Child Development↗
PubMed1994

Import of phosphatidylinositol and phosphatidylcholine into mitochondria of the yeast, Saccharomyces cerevisiae.

An in vitro assay was designed to study the import of 3H-labeled phosphatidylinositol and phosphatidylcholine, respectively, from unilamellar vesicles into isolated mitochondria of the yeast, Saccharomyces cerevisiae. Both phospholipids reached the inner mitochondrial membrane. During import they were detected in contact sites between the outer and the inner mitochondrial membrane, supporting the notion that these zones are sites of intramitochondrial phospholipid transport. The uncoupler CCCP, the antibiotic adriamycin, and energy depletion caused by oligomycin and apyrase did not inhibit the transport of phosphatidylinositol and phosphatidylcholine into mitochondria.

Biological Transport↗
PubMed1993

Further observations on a method for estimating hominoid dental developmental patterns.

Several recent studies have concluded that early hominines resembled apes in patterns of dental ontogeny and have inferred from this conclusion that they were ape-like in other aspects of growth and development as well. Prior to their employment on fossil juveniles, the comparative methods used in these studies were not first tested for their predictive accuracy in distinguishing modern humans from apes on the basis of proposed patterns of dental ontogeny. We find that 92% of a sample of 48 modern children are classified as ape-like or nonhuman by the criteria employed in one of these studies and overlap entirely with fossil juvenile dental patterns. The use of these methods to characterize early hominines as "ape-like" or distinctly divergent from humans is thus shown to be unwarranted.

Animals↗
PubMed1992

Saltation and stasis: a model of human growth.

Human growth has been viewed as a continuous process characterized by changing velocity with age. Serial length measurements of normal infants were assessed weekly (n = 10), semiweekly (n = 18), and daily (n = 3) (19 females and 12 males) during their first 21 months. Data show that growth in length occurs by discontinuous, aperiodic saltatory spurts. These bursts were 0.5 to 2.5 centimeters in amplitude during intervals separated by no measurable growth (2 to 63 days duration). These data suggest that 90 to 95 percent of normal development during infancy is growth-free and length accretion is a distinctly saltatory process of incremental bursts punctuating background stasis.

Aging↗
PubMed1990

Dental caution.

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Animals↗
PubMedDate not supplied

Child factor in measurement dependability.

A primary consideration in longitudinal growth studies is the identification of growth from error components. While previous research has considered matters of measurement accuracy and reproducibility in detail, few reports have investigated the errors of measurement due to aspects of the physiology and cooperation of the child. The present study directly assesses this source of measurement undependability for the first time. Investigation of total measurement error variance in 925 recumbent length replicates taken over stasis intervals in growth identifies that between 60% and 70% of total measurement unreliability is due to a child factor undependability. Individual differences are significant and longitudinal growth analyses should consider two to three times the technical error of measurement statistic as a reasonable estimate of the total unreliability for any single measurement of an infant's recumbent length. These results raise issues regarding analytic methods as applied to serial growth data.

Analysis of Variance↗
PubMedDate not supplied

Mixed distribution analysis identifies saltation and stasis growth.

A maximum likelihood method of mixed distribution analysis is investigated for its utility as a method for the identification of saltation and stasis in longitudinal growth data. Daily infant growth data that have been previously identified to follow a saltatory growth process are employed. This is a novel application of the finite mixed distribution analysis (MDA), a method designed to objectively identify the presence of one or more Gaussian populations. The null hypothesis is that a single Gaussian distribution best describes the incremental growth data. This would be compatible with smooth, slowly varying daily growth patterns. This study explores whether or not two distinctive populations are evident in incremental saltatory growth data, as postulated by the saltation and stasis observations. The analysis is important in providing a growth model-independent test for the presence of saltation and stasis by a separate statistical assessment with none of the saltatory algorithm assumptions. The finite mixed distribution analysis identifies that each individual's incremental growth data is statistically best described as a mixture consisting of two components, or two populations of increments (chi-square, p < 0.05). For each individual, one of these populations is centred about a zero increment, and is compatible with the previous evidence of stasis intervals. The second population of data points is characterized by unique distributions for each individual, compatible with the previous observation that infants grow by unique patterns of growth saltations in both amplitude and frequency. The percentage of data points that fall within each of the two unique finite mixture distributions (FMDs) is similar to the proportions of discrete saltation and stasis intervals previously identified by the saltation and stasis method. Thus, the FMD analysis lends support to the nature of growth as a saltatory process characterized by two states in the daily growth of these infants. By contrast with the saltatory algorithm, which is applied to the original serial growth measurements, the mixed distribution analysis employs increments removed from their time relationships. The lack of time series sequence information precludes the mixed distribution method from reconstructing specific temporal patterns of saltatory growth. The present analysis reiterates that individual growth patterns are statistically unique and cannot be reconstructed or identified from group data.

Biometry↗
PubMedDate not supplied

The use of regularity as estimated by approximate entropy to distinguish saltatory growth.

A nonlinear dynamics metric, approximate entropy (ApEn), is investigated as a diagnostic method for distinguishing between mathematical models, and the underlying mechanistic hypotheses that purport to describe the same time series experimental observations. ApEn measures the occurrence of pattern regularity within a time series, and is used here to investigate growth patterns in daily length growth. The notion investigated is that ApEn distributions for competing time series patterns expressed as mathematical formulations can be modelled by Monte Carlo and bootstrap methods and compared to the ApEn values for an original experimental data series. If the ApEn values for the different models do not overlap, then it is expected that ApEn can be utilized to distinguish these models and hypotheses, and to provide statistical assessment for the underlying biological patterns in experimental data. The conclusion is that the ApEn metric is successful as a time series diagnostic tool. It is a model-independent statistic that clearly differentiates saltatory growth from slowly varying continuous models of growth and serves to further document the saltatory nature of growth. This is a unique application of approximate entropy, illustrating the broad applicability of ApEn to biological time series, with the specific example of discriminating a saltatory growth process in longitudinal growth data. Future investigations of regularity in longitudinal time series in human biology with ApEn statistics are suggested.

Data Interpretation, Statistical↗