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PubMed1982

Repeatability of the moments of the truncated forced expiratory spirogram.

It is proposed that if the spirogram is truncated for moment analysis, this should be done with respect to volume and not time. Errors are incurred when the moments of one spirogram are compared with those of another. These errors are maximal with no truncation and are reduced by truncation. A method is described for deriving sequential truncated moments of the forced expiratory spirogram. The repeatability and discriminatory power of the truncated moments were assessed over five consecutive days in 21 symptom-free subjects and were compared with conventional spirometric tests. The first and second moments about the origin of the spirogram (alpha 1 and alpha 2), the moment ratio (square root alpha 2/alpha 1) and the forced expiratory time to truncation (FET) are progressively less repeatable within individuals the later the truncation point. The discriminatory power of alpha 1 and alpha 2 and FET declines with later truncation but the discriminatory power of the moment ratio is maximal with truncation at 85% forced vital capacity (FVC) an diminishes sharply if truncation is beyond 95% FVC. At 75% FVC truncation alpha 1 is as good as FEV1% in discriminating between our subjects, whereas alpha 1 at 100% FVC is only half as good as FEV1%. The moment ratio at 90% FVC truncation is highly reproducible (mean within person coefficient of variation 2.1%), has important discriminatory power and is little influenced by events early in the spirogram (correlation with FEV1% r = -0.61, p less than 0.001). The moment ratio at 90% of FVC has attributes which may be useful in detecting early airway obstruction and its further study is warranted in order to establish its normal range and predictive value.

Adult↗
PubMed1996

Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors.

Truncated activin type II receptors have been reported to inhibit activin receptor signaling in Xenopus embryos, although the mechanism of action for this effect has not been fully understood. In the present study we demonstrate that in P19 embryonal carcinoma cells both the induction of the activin responsive 3TP-lux reporter construct and the inhibition of retinoic acid-induced neuronal differentiation by activin are blocked by expression of a truncated activin receptor. To reveal the mechanism of action of truncated activin receptors, the interaction between different activin receptors has been investigated upon coexpression in COS cells followed by cross-linking of 125I-activin A and subsequent immunoprecipitation. Complexes between a truncated activin type IIA receptor and activin type IA and type IB receptors can be formed, as demonstrated by coimmunoprecipitation of these type I receptors with the truncated activin type IIA receptor. Other type I receptors known as ALK-1 and ALK-6 also coimmunoprecipitate with the truncated type IIA receptor, whereas ALK-3 and ALK-5 do not. Furthermore, the activin type IIB2 receptor does not coimmunoprecipitate with the truncated type IIA receptor, but decreases activin binding to the truncated type IIA receptor. In double immunoprecipitation experiments with cell lysates from COS cells, in which full-length activin type IIA and type IIB2 receptors were cotransfected, no interaction between these receptors was found. In contrast, homomeric complexes of full-length activin type IIA receptors were detected. These results implicate that truncated activin receptors can interfere with activin signaling by interacting with activin type I receptors. Additionally, truncated activin type IIB2 receptors might also interfere with type IIA receptor signaling by decreasing activin binding to the type IIA receptor and therefore might be more potent in inhibiting activin signal transduction. Furthermore, our data indicate that truncated type IIA receptors can interact with other type I receptors and as such might inhibit signal transduction by type I receptors other than activin type IA and type IB receptors.

Activin Receptors↗
PubMed1989

A comparison of the biological activity of the recombinant intact and truncated insulin-like growth factor 1 (IGF-1).

A truncated form of insulin-like growth factor 1 (IGF-1), which lacked the aminoterminal tripeptide Gly-Pro-Glu has been isolated from human fetal and adult brain. This truncated IGF-1 displayed more potent cross-reactivity and biological action on brain cells than IGF-1 isolated from human serum. We now present data on a recombinant DNA-derived truncated IGF-1 lacking the aminoterminal tripeptide. Recombinant truncated IGF-1 was 1.4-5-times more potent than recombinant and natural IGF-1 in displacing [125 I]IGF-1 from human fetal and adult brain and placenta membranes. These differences were slightly enhanced when truncated IGF-1 was used as radioligand. The relative potencies compared to insulin-like growth factor 2 (IGF-2) in displacing [125I]IGF-2 from rat liver membranes were recombinant truncated IGF-1, 0.3% and recombinant IGF-1, 0.2%. Recombinant truncated IGF-1 displayed 100-fold reduced affinity for the low molecular weight binding protein (IGF-BP) isolated from human amniotic fluid when compared to recombinant IGF-1. Likewise, the IGF-BP was 100-fold less potent in inhibiting the receptor binding of recombinant truncated IGF-1 than that of recombinant IGF-1. Recombinant truncated IGF-1 was 4-times more potent than recombinant and natural IGF-1 in stimulating DNA synthesis in fetal rat brain cells. This biological activity of recombinant truncated IGF-1 was not affected by the IGF-BP at concentrations which abolished the biological activity of recombinant IGF-1. The hypothesis that IGF-BP bound intact IGF-1 represents the endocrine form of IGF-1, whereas truncated IGF-1 represents the paracrine or autocrine form of IGF-1, is proposed.

Animals↗
PubMed2000

On the truncation of long-range electrostatic interactions in DNA.

Long-range interactions are known to play an important role in highly polar biomolecules like DNA. In molecular dynamics simulations of nucleic acids and proteins, an accurate treatment of the long-range interactions are crucial for achieving stable nanosecond trajectories. In this report, we evaluate the structural and dynamic effects on a highly charged oligonucleotide in aqueous solution from different long-range truncation methods. Two group-based truncation methods, one with a switching function and one with a force-switching function were found to fail to give accurate stable trajectories close to the crystal structure. For these group-based truncation methods, large root mean square (rms) deviations from the initial structure were obtained and severe distortions of the oligonucleotide were observed. Another group-based truncation scheme, which used an abrupt truncation at 8. 0 A or at 12.0 A was also investigated. For the short cutoff distance, the conformations deviated far away from the initial structure and were significantly distorted. However, for the longer cutoff, where all necessary electrostatic interactions were included, the trajectory was quite stable. For the particle mesh Ewald (PME) truncation method, a stable DNA simulation with a heavy atom rms deviation of 1.5 A was obtained. The atom-based truncation methods also resulted in stable trajectories, according to the rms deviation from the initial B-DNA structure, of between 1.5 and 1.7 A for the heavy atoms. In these stable simulations, the heavy atom rms deviations were approximately 0.6-1.0 A lower for the bases than for the backbone. An increase of the cutoff radius from 8 to 12 A decreased the rms deviation by approximately 0.2 A for the atom-based truncation method with a force-shifting function, but increased the computational time by a factor of 2. Increasing the cutoff from 12 to 18 A for the atom-based truncation method with a force-shifting function requires 2-3 times more computational time, but did not significantly change the rms deviation. Similar rms deviations from the initial structure were found for the atom-based method with a force-shifting function and for the PME method. The computational cost was longer for the PME method with a cutoff of 12. 0 A for the direct space nonbonded calculations than for the atom-based truncation method with a force-shifting function and a cutoff of 12.0 A. If a nonperiodic boundary, e.g., a spherical boundary, was used, a considerable speedup could be achieved. From the rms fluctuations, the terminal nucleotides and especially the cytidines were found to be more flexible than the nonterminal nucleotides. The B-DNA form of the oligonucleotide was maintained throughout the simulations and is judged to depend on the parameters of the energy function and not on the truncation method used to handle the long-range electrostatic interactions. To perform accurate and stable simulations of highly charged biological macromolecules, we recommend that the atom-based force-shift method or the PME method should be used for the long-range electrostatics interactions.

Base Sequence↗
PubMed2000

Characterization of a human alternatively spliced truncated reduced folate carrier increasing folate accumulation in parental leukemia cells.

Human CEM-7A cells established by gradual deprivation of leucovorin from the growth medium, display 100-fold overexpression of methotrexate transport activity. We found that this was associated with 10-fold reduced folate carrier gene amplification and 50-fold overexpression of both the principal 3 kb reduced folate carrier transcript and, surprisingly, a novel truncated 2 kb reduced folate carrier mRNA poorly expressed in parental CEM cells. The molecular basis for the generation of this truncated reduced folate carrier transcript and its potential functional role in folate accumulation were studied. Reduced folate carrier genomic and cDNA sequencing revealed that the truncated transcript had an internal deletion of 987 nucleotides which was a result of an alternative splicing utilizing a cryptic acceptor splice site within exon 6. This deletion consisted of the 3'-most 480 nucleotides of the reduced folate carrier ORF and the following 507 nucleotides of the 3'-UTR. These resulted in a truncated reduced folate carrier protein, which lacks the C-terminal 160 amino acids, but instead contains 58 new C-terminal amino acids obtained from reading through the 3'-UTR. Consequently, a truncated reduced folate carrier protein is generated that lacks the 12th transmembrane domain and contains a new and much shorter C-terminus predicted to reside at the extracellular face. Western analysis with plasma-membrane fraction from CEM-7A cells revealed marked overexpression of both a broadly migrating approximately 65-90 kDa native reduced folate carrier and a approximately 40-45 kDa truncated reduced folate carrier, the core molecular masses of which were confirmed by in vitro translation. However, unlike the native reduced folate carrier, the truncated reduced folate carrier protein failed to bind the affinity labels NHS-[3H]MTX and NHS-[3H]folic acid. Stable transfection of the truncated reduced folate carrier cDNA into mouse L1210 leukemia cells: increased folate accumulation, decreased their leucovorin and folic acid growth requirements, and increased their sensitivity to methotrexate. This constitutes the first documentation of an expressed alternatively spliced truncated reduced folate carrier that, when coexpressed along with the native carrier, augments folate accumulation and consequently decreases the cellular folate growth requirement. The possible mechanisms by which the truncated reduced folate carrier may increase folate accumulation and/or metabolism in cells coexpressing the truncated and native reduced folate carrier are discussed.

3' Untranslated Regions↗
PubMed1989

The effects of truncating long-range forces on protein dynamics.

This paper considers the effects of truncating long-range forces on protein dynamics. Six methods of truncation that we investigate as a function of cutoff criterion of the long-range potentials are (1) a shifted potential; (2) a switching function; (3) simple atom-atom truncation based on distance; (4) simple atom-atom truncation based on a list which is updated periodically (every 25 steps); (5) simple group-group truncation based on distance; and (6) simple group-group truncation based on a list which is updated periodically (every 25 steps). Based on 70 calculations of carboxymyoglobin we show that the method and distance of long range cutoff have a dramatic effect on overall protein behavior. Evaluation of the different methods is based on comparison of a simulation's rms fluctuation about the average coordinates, the rms deviation from the average coordinates of a no cutoff simulation and from the X-ray structure of the protein. The simulations in which long-range forces are truncated by a shifted potential shows large rms deviations for cutoff criteria less than 14 A, and reasonable deviations and fluctuations at this cutoff distance or larger. Simulations using a switching function are investigated by varying the range over which electrostatic interactions are switched off. Results using a short switching function that switches off the potential over a short range of distances are poor for all cutoff distances. A switching function over a 5-9 A range gives reasonable results for a distance-dependent dielectric, but not using a constant dielectric. Both the atom-atom and group-group truncation methods based on distance shows large rms deviation and fluctuation for short cutoff distances, while for cutoff distances of 11 A or greater, reasonable results are achieved. Although comparison of these to distance-based truncation methods show surprisingly larger rms deviations for the group-group truncation, contrary to simulation studies of aqueous ionic solutions. The results of atom-atom or group-group list-based simulations generally appear to be less stable than the distance-based simulations, and require more frequent velocity scaling or stronger coupling to a heat bath.

Algorithms↗
PubMed1992

Lengths of truncated forms of apolipoprotein B (apoB) determine their intestinal production.

Most truncations of apoB associated with hypobetalipoproteinemia (HBL) result from frame shift mutations of the apoB gene that give rise to premature stop codons and truncations of C-terminal sequences. The "natural" truncation, apoB-48, arises from a stop codon by cotranscriptional editing of intestinal apoB-100 mRNA. We hypothesized that mutant apoB mRNA would be normally edited and that only those apoB truncations shorter than apoB-48 would be expressed in enterocytes, because translation of mRNAs giving rise to longer truncations would be interrupted by the apoB-48 stop codon. Duodenal mucosal biopsies from HBL and normolipidemic subjects were incubated with [35S]methionine, apoB was immunoprecipitated and bands were visualized by autoradiography. Biopsies of three subjects heterozygous for apoB-54.8 or apoB-89 synthesized virtually only apoB-48. By contrast, the biopsy of a subject heterozygous for apoB-40 synthesized both apoB-48 and apoB-40. Thus, enterocytes in HBL edit the mutant mRNAs similarly to the apoB mRNA of normal enterocytes and the small intestine of heterozygotes with truncations longer than apoB-48 produce only apoB-48, as the apoB-48 stop codon terminates translation proximal to the mutant stop codon. By contrast, intestines of heterozygotes with truncations shorter than apoB-48 produce the truncated apoB because the mutant stop codon stops translation before the apoB-48 stop codon. In conclusion, only the liver secretes apoB truncations larger than apoB-48, whereas shorter truncations are secreted by both liver and intestine.

Apolipoproteins B↗
PubMedDate not supplied

Transmission scan truncation with small-field-of-view dedicated cardiac SPECT systems: impact and automated quality control.

BACKGROUND: Small-field-of-view (FOV) dedicated cardiac single photon emission computed tomography (SPECT) systems will frequently exhibit severe transmission scan truncation that may degrade attenuation correction (AC). This study evaluated the impact of transmission scan truncation on AC and developed automated transmission scan truncation quality control (ATSTQC) for small-FOV systems. METHODS AND RESULTS: Small-FOV data were simulated from the data of 10 patients acquired by a full-FOV Philips Vertex system. AC images of the full- and small-FOV data were compared by mean and maximum absolute differences of myocardial counts, and differences in stress and rest severity scores were calculated by use of the Emory Cardiac Toolbox.small-FOV systems. ATSTQC was developed to identify critical truncation that significantly increased these indices and then tested with 18 independent patients. Left-side truncation resulted in significant distortion of the quantitative indices. ATSTQC, developed on the condition that left-side truncation is critical, showed high concordance with the qualitative assessment in identification of critical truncation. CONCLUSIONS: Identification of left-side truncation as critical truncation is necessary to judge whether accurate AC can be obtained. The developed ATSTQC can accurately detect critical truncation and will help clinicians decide whether to use AC in a particular study.

Artifacts↗
PubMed1990

Circulating forms and biological activity of intact and truncated insulin-like growth factor I in adult and neonatal rats.

A variant of IGF-I with a truncated aminoterminal region has been isolated and shown to display increased biological activity in vitro, but weak affinity of binding to the IGF binding proteins compared with intact IGF-I. In the present study, the circulating molecular forms and biological activity of intact and truncated IGF-I were compared after in vivo administration. Adult and 10-day-old rats were given 125I-truncated or 125I-intact IGF-I iv. In both adult and 10-day-old rats 125I-truncated IGF-I showed weaker affinity of binding to the IGF binding proteins and greater degradation than 125I-intact IGF-I. Serum half-life was 2 h for 125I-truncated IGF-I and 3 h for 125I-intact IGF-I in adult rats. The half-life in 10-day-old rats was 20.5 min for 125I-truncated IGF-I and 27 min for 125I-intact IGF-I. The uptake of 125I-truncated IGF-I into the kidney, liver and brain of 10-day-old rats was significantly higher than for 125I-intact IGF-I 15 min after iv administration. The insulin-like effects of the IGF-I peptides were examined in vitro and in vivo. Truncated IGF-I stimulated [3-3H]glucose incorporation into free fatty acids in adipocytes in vitro to a greater extent than did intact IGF-I. In vivo administration of both intact and truncated IGF-I to adult rats significantly decreased serum glucose levels and significantly increased the incorporation of [U-14C]glucose into glycogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1998

Effect of truncated projections on defect detection in attenuation-compensated fanbeam cardiac SPECT.

UNLABELLED: For some camera systems used in cardiac SPECT, the limited field of view of fanbeam-collimated detectors produces truncation in the projection data. This truncation may generate artifacts and distortions in the transmission CT images and in the attenuation-corrected myocardial SPECT images (that use the transmission CT images as attenuation maps), thus affecting clinical diagnosis. Concern over this problem stimulated us to evaluate the effect of truncation with human observer performance studies. METHODS: A three-dimensional mathematical cardiac-torso phantom that realistically models the attenuation and 201Tl uptake distributions in different organs of the upper torso was used for the investigation. Five degrees of truncation (from 0% to 40% truncation) in the projection data were simulated by the use of five different detector sizes collimated by fanbeam collimators. The attenuation maps were obtained by reconstructing the truncated transmission data generated from these fanbeam geometries. The emission data obtained with the same fanbeam geometries were reconstructed by using the maximum likelihood-expectation maximization algorithm and were corrected for attenuation using the reconstructed attenuation maps. Two observer performance studies were performed. In Study 1, the images were reconstructed without using the body contour as support, whereas in Study 2, the exact body contour was used in reconstructing both the attenuation maps and the attenuation-corrected SPECT images. RESULTS: The results of the receiver operating characteristics analysis indicate that there is very little difference between detection for the various degrees of truncation, and this difference only becomes noticeable for severe truncation of greater than 40%. CONCLUSION: Using the acquisition and processing methods, we found the use of the body contour as support in reconstructing truncated transmission CT and SPECT data reduces the loss of defect detectability in attenuation-compensated myocardial SPECT images due to truncated data.

Algorithms↗
PubMed2003

Cloning of a C-terminally truncated NK-1 receptor from guinea-pig nervous system.

In order to examine the possibility that some actions of substance P may be mediated by a variant of the neurokinin-1 (NK-1) receptor, we isolated and sequenced the cDNA encoding a truncated NK-1 receptor from guinea-pig celiac ganglion and brain mRNA by two-step RT-PCR based on the 3'RACE method. The truncated NK-1 receptor sequence corresponded to a splice variant missing the final exon 5, and encoded a 311-amino acid protein that was truncated just after transmembrane domain 7, in an identical position to a truncated variant of the human NK-1 receptor. Thus, the truncated NK-1 receptor lacked the intracellular C-terminus sequence required for the phosphorylation and internalisation of the full-length NK-1 receptor. Using a sensitive one-step semi-quantitative RT-PCR assay, we detected mRNA for both the full length and truncated NK-1 receptors throughout the brain, spinal cord, sensory and autonomic ganglia, and viscera. Truncated NK-1 receptor mRNA was present in lower quantities than mRNA for the full-length NK-1R in all tissues. Highest levels of mRNA for the truncated NK-1 receptor were detected in coeliac ganglion, spinal cord, basal ganglia and hypothalamus. An antiserum to the N-terminus of the NK-1 receptor labelled dendrites of coeliac ganglion neurons that were not labelled with antisera to the C-terminus of the full length NK-1 receptor. These results show that a C-terminally truncated variant of the NK-1 receptor is likely to be widespread in central and peripheral nervous tissue. We predict that this receptor will mediate actions of substance P on neurons where immunohistochemical evidence for a full-length NK-1 receptor is lacking.

Alternative Splicing↗
PubMed1994

Truncation of the cytoplasmic domain of the simian immunodeficiency virus envelope glycoprotein alters the conformation of the external domain.

We previously reported that truncation of the cytoplasmic domain of the macaque simian immunodeficiency virus SIVmac239 envelope glycoprotein enhanced its ability to induce cell fusion in a variety of cell lines. In the present study, we examined the expression of the full-length and truncated SIVmac239 envelope glycoprotein complex on cell surfaces. Using a membrane-impermeable reagent to biotinylate proteins on cell surfaces followed by immunoprecipitation, we found that under conditions in which the full-length TM protein could not be detected on the surfaces of CD4-positive or CD4-negative cell lines, the truncated TM protein was detected efficiently. In contrast, using a membrane-impermeable iodination reagent to label proteins on cell surfaces, we could detect both the full-length and truncated TM proteins. No difference between the full-length and truncated proteins was observed in the detection of the SU proteins in the biotinylation assay. Additionally, we used an assay in which SIV-specific antibodies are prebound to the native envelope proteins expressed on the cell surface and then the proteins are immunoprecipitated. Using this assay, we could not detect the truncated or full-length TM protein on the cell surface, whereas we could detect the SU subunits of both proteins. We also observed that the truncated TM protein formed more stable sodium dodecyl sulfate-resistant oligomers than the full-length TM protein did. These results indicate that truncation of the cytoplasmic domain of the SIVmac239 envelope glycoprotein affects the conformation of the external domain of the TM protein on the cell surface, even though the two proteins have no differences in the amino acid sequences of their external domains. This altered conformation could play a role in the enhanced fusion activity of the truncated SIV glycoprotein.

Antibodies, Viral↗
PubMed1997

Organ loci of catabolism of short truncations of apoB.

Truncations of apolipoprotein (apo) B shorter than 3200 amino acids (3200/4536 = apoB-70) do not possess the LDL receptor-recognition domain and are not recognized by altered cells with normally functioning LDL receptors. To ascertain which organs remove such truncated apoB-containing particles, we isolated apoB-31-, apoB-38.9-, and apoB-43.7-containing particles from plasmas of familial hypobetalipoproteinemia heterozygous humans by a combination of sequential ultracentrifugation and preparative electrophoresis. Particles with labeled 125I- or 131I-dilactitol tyramine (I-DLT), were injected into New Zealand White rabbits, along with I-DLT-apoB-100-containing LDLs, and the decay of 125I- and 131I-TCA-precipitated counts was followed over 24 hours. At the end of 24 hours, rabbits were anesthetized and their bodies perfused. Organs were removed and homogenized, and TCA-precipitable counts determined. Fractional catabolic rates of apoB truncation particles were two to five times greater than those of apoB-100 LDLs. ApoB truncations accumulated in adrenals at one fifth the rates of apoB-100 LDL, compatible with the functional absences of LDL receptor-recognition domains in truncated apoBs. The major organ of uptake for apoB-100-LDLs was the liver, whereas truncation particles were readily removed by the kidney (kidney: liver uptake ratios were 0.10 to 0.30 for apoB-100 LDLs and 1.03 to 3.77 for truncations). Spleens accumulated little of either apoB-100 or truncation particles, suggesting particles were not "damaged" or aggregated. Thus, the absence of > 56% of the carboxyl end of apoB-100 increases the plasma clearance and redirects the organ uptake of the apoB truncation-containing lipoproteins from liver to kidney.

Adult↗
PubMed2001

Novel, aberrantly truncated isoform of serum CD13 in a family with high serum aminopeptidase N (CD13) activity.

BACKGROUND: We previously reported a family in which the propositus and both her father and paternal grandmother had high serum aminopeptidase N (CD13; EC 3.4.11.2) activity (autosomal dominant). The molecular mass of the serum CD13 polypeptide of the propositus was larger than that of normal CD13, suggesting either a mutation in the CD13 gene or an abnormality in posttranslational modification of CD13 polypeptide in this family. METHODS: Reverse transcription-PCR and direct sequencing were performed with leukocyte CD13 mRNA from the propositus. Two-dimensional electrophoresis and N-terminal amino acid sequencing were performed with serum CD13 from the propositus, the father of the propositus, and healthy volunteers. RESULTS: The sequence of the CD13 cDNA of the propositus was essentially identical with that reported previously. However, the CD13 polypeptide of the propositus and the father of the propositus was truncated, lacking amino acids 1-43 of intact CD13 (43-truncated CD13), whereas CD13 lacking residues 1-58 (58-truncated CD13) and 43-truncated CD13 were detected in serum from healthy volunteers. CONCLUSIONS: In serum from healthy volunteers, we found both 58-truncated CD13, a major isoform reported previously, and 43-truncated CD13, a novel, minor isoform with a larger polypeptide. In serum of the family, 43-truncated CD13 was extremely concentrated, suggesting that proteolytic cleavage of CD13 amino acids 43 and 44 (43-truncation) is abnormally promoted. Because no mutation was found in the CD13 cDNA from the propositus, increased serum CD13 in this family seems to be caused by a mutation in a gene that regulates 43-truncation protease activity.

Adult↗
PubMed2000

Amyloid beta-protein (Abeta)-containing astrocytes are located preferentially near N-terminal-truncated Abeta deposits in the human entorhinal cortex.

The deposition of the amyloid beta-protein (Abeta) is a pathological hallmark of Alzheimer's disease (AD). Abeta is a peptide consisting of 39-43 amino acids and is derived by beta- and gamma-secretase cleavage from the Abeta protein precursor (AbetaPP). An N-terminal-truncated form of Abeta can occur following alpha- and gamma-secretase cleavage of AbetaPP. Fleecy amyloid is a recently identified distinct type of Abeta deposits occurring in the internal layers (pri-alpha, pri-beta and pri-gamma) of the human entorhinal cortex. Fleecy amyloid consists exclusively of N-terminal-truncated Abeta and is a transient form of Abeta deposits, which disappears in late-stage beta-amyloidosis. In this study, the entorhinal cortex of 15 cases with AD-related pathology was used to examine astrocytes in the vicinity of N-terminal-truncated Abeta in fleecy amyloid of the layers pri-alpha, pri-beta, and pri-gamma in comparison to astrocytes in the vicinity of full-length Abeta in layers pre-beta and pre-gamma. Immunohistochemistry was performed with antibodies directed against AbetaPP, Abeta40, Abeta42, APbeta17-24, Abeta1-17 and Abeta8-17 as well as by double-labeling with antibodies directed against Abeta17-24, Abeta42, and glial fibrillary acid protein (GFAP). A large number of GFAP-positive astrocytes containing N-terminal-truncated Abeta fragments appeared in the vicinity of N-terminal-truncated Abeta, whereas Abeta-containing astrocytes were rarely seen in the vicinity of full-length Abeta. These results suggest that N-terminal-truncated Abeta peptide may be cleared preferentially from the extracellular space by astrocytic uptake and processing. Such an astroglial uptake of N-terminal-truncated Abeta may account for the transient nature of fleecy amyloid and point to the use of N-terminal truncation of Abeta in potential therapeutic strategies aimed at preventing the brain from amassing full-length Abeta deposits.

Aged↗
PubMed1993

Molecular cloning and expression of a novel truncated form of chicken trkC.

The trk family of tyrosine protein kinase genes serves crucial roles for the development of the nervous system and the survival of neurons. The members of this gene family, trk, trkB and trkC, bind a distinct neurotrophin of the nerve growth factor (NGF) gene family, and trigger the intracellular signals which elicit trophic and differentiating effects on neurons. Adding to these neurotrophic receptor kinases, the truncated forms without the tyrosine kinase domain have been cloned and characterized. It has been thought that the existence of truncated forms is limited to trkB; however, very recently the truncated trkC has been cloned in rat [(1993) Neuron 10, 963-974; (1993) Neuron 10, 975-990]. We independently approached and molecularly cloned a truncated form which belongs to the chicken trkC. The truncated trkC possesses the binding and the transmembrane domains but not the tyrosine kinase domain. Northern blot analysis shows that the truncated form is preferentially expressed in the adult central nervous system. The truncated form is scarcely expressed during the embryonic stages. The conservation of the truncated trkC beyond species suggests they have specific functions.

Amino Acid Sequence↗
PubMed1992

Inhibitory effects of N- and C-terminal truncated Escherichia coli recA gene products on functions of the wild-type recA gene.

The effects of the expression of Escherichia coli truncated RecA protein on the host recA functions were examined. The recA gene on a multicopy plasmid was manipulated to express the truncated RecA protein from its carboxyl (C) and amino (N) terminal ends where a maximum of four extra amino acid residues was added. The regulatory part of the recA gene was substituted by the lacUV5 promoter in the plasmid to facilitate the artificial control of recA expression. Enzyme-linked immunosorbent assay and Western blot analyses revealed great differences in accumulation of the truncated RecA proteins in the cell, depending on the location of the site of truncation. The expression of truncated proteins lacking 62, 77, 93 or 149 amino acid residues from the C-terminal end caused the host recA+ wild-type cell to become sensitive to ultraviolet irradiation and interfered with chromosomal recombination but did not interfere with the induction of lambda prophage. The expression of truncated RecA protein with 25 amino acid residues deleted from the C-terminal end caused the host cell to induce SOS functions constitutively. Truncated RecA proteins with 15 or 28 amino acid residues missing from the N-terminal end severely interfered with all of the host recA functions examined here. The effect of the loss of 41 amino acid residues from the N-terminal end of RecA was significant but less than the effect of proteins lacking 15 or 28 amino acid residues from the N-terminal end. A protein lacking 59 amino acid residues from the N-terminal end showed little interference with any measured recA functions, suggesting that the deletion of the region from around residues 41 to 59, which is rich in hydrophobic side-chains, influenced the ability of the truncated protein to interfere with the functions of wild-type RecA protein. We also constructed a mutant gene with an internal deletion whose product was missing a region from residues 184 to 204. That mutant RecA protein was stably accumulated in the cell. This protein had little effect on the function of host wild-type recA gene product. The possible function of the regions at the N and C termini are discussed.

Base Sequence↗
PubMed1995

Human cystatin A is inactivated by engineered truncation. The NH2-terminal region of the cysteine proteinase inhibitor is essential for expression of its inhibitory activity.

A series of NH2-terminal truncated forms of human cysteine proteinase inhibitor, cystatin A, was prepared by genetic engineering using Escherichia coli harboring mutated genes. Each variant of cystatin A was efficiently expressed as a fused protein with porcine adenylate kinase and released by CNBr degradation after exchange of the sole inner Met to Leu. The mutant cystatin A lacking an amino-terminal Met residue (called standard variant starting from Ile2, CystA2-98(M65L) showed the same inhibitory activity as authentic one isolated from human epidermis. Two-residue truncation scarcely influenced the activity, but further truncations deleting Pro3 and beyond conservative Gly4 and Gly5 caused a remarkable decrease of their inhibitory activity. But little effect was observed by a substitution of Pro3 with Leu. The loss of the activity by amino-terminal truncation was compensated slightly by engineered substitution of Gly75 with His on a second loop. In the two-dimensional 15N-1H HSQC NMR spectrum, four-residue truncation was found to cause changes in the chemical shifts of Val47 and Val48, which locate on a first loop and consist of a conservative QVVAG sequence. Furthermore, the truncation led to a change in fluorescence spectroscopic behavior of Trp75, which was introduced as a probe on the second loop. Fluorescence intensity of the Trp of the truncated (5-98) form was more affected by heating than the active standard variant. Conversely, fluorescence of Trp75 in 2-98 form was more quenched by acrylamide than the 5-98 variant. Thus, the amino-terminal region of cystatin A is essential for the expression of its inhibitory activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗