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Structure of the knob protein (KP) gene of Plasmodium falciparum.

We have determined the nucleotide sequence of the gene encoding the knob protein (KP) of Plasmodium falciparum (FCR-3/Gambia). The gene is interrupted by an intron which contains 34 imperfect tandemly repeated ATTTT sequences. The first exon encodes 33 amino acids with a hydrophobic core typical of signal peptides. The second exon has an open translational reading frame for 597 amino acids. The deduced protein sequence indicates that KP has multiple structural domains; unlike the N-terminal histidine-rich domain which we described previously, the C-terminal half is rich in lysine residues. Consistent with the apparent association of KP with the cytoplasmic surface of the host erythrocyte membrane, the protein is highly charged and hydrophilic.

Amino Acid Sequence↗

Nested genomic structure of haploid germ cell specific haspin gene.

The haspin gene specifically expressed in haploid germ cells encodes a unique Ser/Thr protein kinase. We have cloned a mouse haspin genomic clone using cDNA as a probe. Sequencing data showed that the haspin gene was not interrupted by introns and was bordered by appropriate direct repeat. The transcription start site of the gene was not preceded by a TATA box. The whole transcription unit was located at an intron of integrin alphaM290 gene, and transcription direction of these two genes was different. Southern blotting analysis under stringent condition showed that haspin was a single gene. Phylogenetic analysis suggested that the diversion of haspin gene from other kinase family might be very ancient: the early stage of plant-fungus-animal split.

Animals↗

A P element-homologous sequence in the house fly, Musca domestica.

Sequences homologous to the P transposable element have been identified in Musca domestica. Sequence analysis of a genomic clone (Md-P1) indicates that, although the house fly P element has lost its coding capacity, the basic general structure of drosophilid P elements is present. The house fly P element sequence shares a number of structural features with that from the blow fly, Lucilia cuprina, including a large intron separating exons 1 and 2, two additional introns interrupting exon 2 and the apparent absence of inverted repeat termini. Within a relatively well-conserved central region, the house fly sequence shows 59% similarity to the D. melanogaster P element, but distal regions are more diverged. Southern blot analysis of several strains indicated the presence of at least four P element copies.

Amino Acid Sequence↗

Ectodysplasin is a collagenous trimeric type II membrane protein with a tumor necrosis factor-like domain and co-localizes with cytoskeletal structures at lateral and apical surfaces of cells.

Anhidrotic ectodermal dysplasia (EDA) is a human genetic disorder of impaired ectodermal appendage development. The EDA gene encodes isoforms of a novel transmembrane protein, ectodysplasin. The sequence of the longest isoform includes an interrupted collagenous domain of 19 Gly-X-Y repeats and a motif conserved in the tumor necrosis factor (TNF)-related ligand family. In order to understand better the function of the ectodysplasin protein molecule and its domains, we have studied the processing and localization of wild-type and mutated isoforms in transfected human fetal kidney 293 and monkey kidney COS-1 cells. Similar to other members of collagenous membrane proteins and members of TNF-related ligands, ectodysplasin is a type II membrane protein and it forms trimers. The membrane localization of ectodysplasin is asymmetrical: it is found on the apical and lateral surfaces of the cells where it co-localizes with cytoskeletal structures. The TNF-like motif and cysteines found near the C-terminus are necessary for correct transport to the cell membrane, but the intracellular and collagenous domains are not required for the localization pattern. Our results suggest that ectodysplasin is a new member in the TNF-related ligand family involved in the early epithelial-mesenchymal interaction that regulates ectodermal appendage formation.

Amino Acid Sequence↗

Mantram repetition for stress management in veterans and employees: a critical incident study.

AIM: This paper reports a study assessing the usefulness of a mantram repetition programme. BACKGROUND: Complementary/alternative therapies are becoming commonplace, but more research is needed to assess their benefits. A 5-week programme teaching a 'mind-body-spiritual' technique of silently repeating a mantram - a word or phrase with spiritual meaning - to manage stress was developed. A mantram was chosen by individuals, who were taught to repeat it silently throughout the day or night to interrupt unwanted thoughts and elicit the relaxation response. METHODS: Participants who attended a 5-week course were invited to participate in the study. Of those who consented, a randomly selected subset (n = 66) was contacted approximately 3 months after the course for a telephone interview using the critical incident interviewing technique. Participants were asked whether the intervention was helpful or not, and if helpful, to identify situations where it was applied. Interviews were transcribed and incidents were identified and categorized to create a taxonomy of uses. The data were collected in 2001-2002. RESULTS: Participants included 30 veterans, mostly males (97%), and 36 hospital employees, mostly females (86%). Mean age was 56 years (sd = 12.94). Fifty-five participants (83.3%) practiced the technique and reported 147 incidents where the programme was helpful. Outcomes were organized into a taxonomy of incidents using four major categories that included managing: (a) emotions other than stress (51%); (b) stress (23.8%); (c) insomnia (12.9%); and (d) unwanted thoughts (12.3%). A group of raters reviewed the categories for inter-rater reliability. CONCLUSIONS: The majority of participants from two distinct samples reported that the mantram programme was helpful in a variety of situations. The critical incident interviewing method was found to be practical, efficient, and thorough in collecting and analyzing data. Such qualitative methods contribute to understanding the benefits of mind-body complementary therapies.

Adult↗

Complex multiple antibiotic and mercury resistance region derived from the r-det of NR1 (R100).

The sequence of the 45.2-kb multidrug and mercury resistance region of pRMH760, a large plasmid from a clinical isolate of Klebsiella pneumoniae collected in 1997 in Australia, was completed. Most of the modules found in the resistance determinant (r-det), or Tn2670, region of NR1 (also known as R100), isolated from a Shigella flexneri strain in Japan in the late 1950s, were present in pRMH760 but in a different configuration. The location was also different, with the Tn2670-derived region flanked by the transposition module of Tn1696 and a mercury resistance module almost identical to one found in the plasmid pDU1358. This arrangement is consistent with a three-step process. First, the r-det was circularized via homologous recombination between the IS1 elements and reincorporated at a new location, possibly in a different plasmid, via homologous recombination between the 5'-conserved (5'-CS) or 3'-CS of the In34 integron in the r-det and the same region of a second class 1 integron in a Tn1696 relative. Subsequently, resolvase-mediated recombination between the res sites in the r-det and a second mercury resistance transposon removed one end of the Tn1696-like transposon and part of the second transposon. Other events occurring within the r-det-derived portion have also contributed to the formation of the pRMH760 resistance region. Tn2 or a close relative that includes the bla(TEM-1b) gene had moved into the Tn21 mercury resistance module with subsequent deletion of the adjacent sequence, and all four 38-bp inverted repeats corresponding to Tn21 family transposon termini have been interrupted by an IS4321-like element.

Anti-Bacterial Agents↗

Analysis of the distal 5' region of the human CYP17 gene.

In order to search for additional regulatory elements in the human CYP17 (steroid 17 alpha-hydroxylase) gene and to compare it with potential regulatory elements in bovine CYP17 genes, 3.5 kb of 5' flanking region of CYP17 was cloned and analyzed. The newly acquired sequence was shown to be a highly defective copy of the human endogenous retrovirus HERV-K family. This retroviral sequence was itself interrupted by a novel element, a low copy number repeat occurring about 20 times in the human genome, including a known copy in the human catechol-O-methyltransferase gene. A reanalysis of the entire 5' flanking region of human CYP17 indicates that only the 300 bp immediately distal to the promoter is of unique sequence; other regulatory sequences, including any that are similar to the upstream region of the bovine genes, are unlikely to occur within 5.5 kb of the promoter.

Aldehyde-Lyases↗

Coordination of swallowing and respiration in unconscious subjects.

We investigated the coordination of swallowing and breathing in 11 unconscious patients with an endotracheal tube in place during the recovery period from general anesthesia. Swallows occurred during both the inspiratory and expiratory phases with no preponderant occurrence during either phase. When a swallow occurred during inspiration, the inspiration was interrupted immediately and was followed by expiration, but the durations of both inspiration and expiration were progressively increased as the time from the onset of inspiration to the onset of swallowing was progressively delayed. A swallow coinciding with the expiratory phase progressively prolonged the duration of the expiration that had been interrupted as the timing of swallowing was progressively delayed. Repeated swallows invariably and in a predictable manner caused changes in the breathing pattern. Thus when the frequency of regularly repeated swallows was relatively high, the breathing pattern was characterized by regular, shallow, and rapid breaths. When the frequency of regularly repeated swallows was relatively low, the breathing pattern was characterized by regular, deep, and slow breaths. When the frequency of repeated swallows was irregular, the breathing patterns were characterized by inconsistent changes in tidal volume and respiratory frequency. Our results indicate that, in unconscious subjects, some mechanisms integrating respiration and swallowing are operative and responsible for changes in breathing patterns during swallowing.

Adult↗

Estimating the duration of Plasmodium falciparum infection from trials of indoor residual spraying.

We reviewed the use of simple mathematical models to estimate the duration of Plasmodium falciparum infection after transmission has been interrupted. We then fit an exponential decay model to repeated cross-sectional survey data collected from three historical trials of indoor residual spraying against malaria: one from two contiguous districts in Tanzania-Kenya (Pare Taveta) carried out in 1954, the others in West Papua (1953), and the Garki project in northern Nigeria (1972-1973). A cross-sectional analysis of these datasets gave overall estimates of 602 days (95% confidence interval [CI] = 581-625) for the infection duration in Pare Taveta, 734 days (95% CI = 645-849) in West Papua, and 1,329 days (95% CI =1,193-1,499) for Garki. These estimates are much greater than the most widely quoted figures for the duration of untreated P. falciparum infections. Although these may be exaggerated because some reinfections occurred despite intensive vector control, prevalence was still decreasing when all these projects ended. Longitudinal survival analysis of the Garki data gave much shorter estimates of duration (186 days, 95% CI = 181-191), but effects of imperfect detection of parasites by microscopy severely bias these estimates. Estimates of infection duration for different age groups showed considerable variation but no general age trend. There was also no clear relationship between malaria endemicity and infection duration. Analyses of successive sampling from the same individuals with parasite typing are needed to obtain more reliable estimates of infection duration in endemic areas. Periods of several years may be required to evaluate long-term effects of interventions on malaria prevalence.

Animals↗

Drosophila laminin A chain sequence, interspecies comparison, and domain structure of a major carboxyl portion.

Recent studies ascribed some biological actions of cell adhesion and cell outgrowth to the carboxyl-most 1200 amino acids of vertebrate laminin A chains. Here we report a 6.1-kilobase pair nucleotide cDNA sequence encoding 1951 amino acids and the carboxyl end of a Drosophila laminin A chain. It corresponds to the mouse laminin A domains G, I, II, and III, but may represent a different type of laminin A chain. The arrangement of the cysteine-rich repeats of domain III resembles that of B2 chains. However, it has more amino acid identity with a portion of the mouse laminin A chain domain IIIb than with other laminin repeats. Domains I and II are consistent with an interrupted coiled-coil alpha-helical model of the long arm of laminin but are poorly conserved. The G domain contains five subdomains which are individually related to subdomains of vertebrate laminin A chains. The results indicate that laminin G subdomains should be considered individually, rather than merely as parts of a G-globule. A sequence of hydroxyamino acids contributes to a spacer between two of the subdomains. Stretches of hydroxyamino acids may be indicative of junctions between domains of extracellular Drosophila proteins.

Amino Acid Sequence↗

[Treatment of acute thromboses and embolisms of the arteries of the extremities in cardiosclerosis patients].

An experience with the surgical and conservative treatment of 196 patients with acute thromboses and embolism of the extremity arteries in patients with arteriosclerotic and postinfarction cardiosclerosis has shown the conservative treatment of arterial embolism to have little effect. Results of the surgical treatment were regularly better in patients admitted to the hospital at earlier terms after acute occlusion of the vessel, with mild ischemia and the absence of a considerable atherosclerotic lesion of the extremity interrupting the major blood flow. For prophylactics of a repeated embolism of considerable significance were found to be correcting operations on the heart and the continuous anticoagulating therapy.

Acute Disease↗

[How and why treat supraventricular tachycardias].

The present study deals with pathophysiological and clinical aspects of two major supraventricular tachyarrhythmias: atrial fibrillation and reciprocating tachycardia. The main hemodynamic effects and the most frequent complications are examined, and therapeutic indications are given concerning pharmacologic, surgical or electrical treatment. Twelve patients with supraventricular tachycardia (5 with intranodal reentry and 7 with A-V by-pass tract) were treated with Propafenone and evaluated by repeated electrophysiological testing. Acute infusion of Propafenone (2 mg/kg over 10 minutes) interrupted the induced tachycardia in 9 of 11 patients (81%); Propafenone prevented the induction of the arrhythmia in 60% of patients with nodal reentry and in none with A-V by-pass. Electrophysiological evaluation repeated after one week of oral treatment (300 mg three times daily) in 5 patients indicated complete protection in two patients; in three the arrhythmia was still inducible but had a significantly lower rate. Finally, with regard to electrical treatment, data are presented concerning 10 patients with supraventricular reentrant tachycardia (4 intranodal, 6 with A-V by-pass tract) in whom an antiarrhythmic pacemaker was implanted (5 type Pasar Telectronics, 5 type Medtronic SP 500). The results were highly favourable in 9 patients with complete control of the arrhythmia.

Anti-Arrhythmia Agents↗

Long terminal repeat-like elements flank a human immunoglobulin epsilon pseudogene that lacks introns.

There are at least three immunoglobulin epsilon genes (C epsilon 1, C epsilon 2, and C epsilon 3) in the human genome. The nucleotide sequences of the expressed epsilon gene (C epsilon 1) and one (C epsilon 3) of the two epsilon pseudogenes were compared. The results show that the C epsilon 3 gene lacks the three intervening sequences entirely and has a 31-base A-rich sequence 16 bases 3' to the putative poly(A) addition signal, indicating that the C epsilon 3 gene is a processed gene. The C epsilon 3 gene sequence is homologous to the five separate DNA segments of the C epsilon 1 gene; namely, a segment in the 5'-flanking region (100 bases) and four exons, which are interrupted by a spacer region or intervening sequences. Long terminal repeat (LTR)-like sequences which contain TATAAA and AATAAA sequences as well as terminal inverted repeats are present in both 5'- and 3'-flanking regions. The 5' and 3' LTR-like sequences do not, however, constitute a direct repeat, unlike transposable elements of eukaryotes and retroviruses. The 3' LTR-like sequence is repetitive in the human genome, but is not homologous to the Alu family DNA. Models for the evolutionary origin of the processed gene flanked by the LTR-like sequences are discussed. The C epsilon 3 gene has a new open frame which codes potentially for an unknown protein of 292 amino acid residues.

Amino Acid Sequence↗

Consensus inverted terminal repeat sequence of Paramecium IESs: resemblance to termini of Tc1-related and Euplotes Tec transposons.

During the formation of a transcriptionally active macronucleus, ciliated protozoa excise large numbers of interstitial segments of DNA (internal eliminated sequences; IESs) from their chromosomes. In this study we analyze the published sequences of 20 IESs that interrupt surface protein genes of Paramecium and identify a consensus inverted terminal repeat. This sequence is similar to the ends of the Tc1-related transposons found in nematodes and other metazoans, as well as to both the ends of the Tec transposons and at least some of the IESs in the distantly related ciliate Euplotes crassus. The results of these analyses bolster previous proposals that IESs were created by transposition.

Animals↗

Inhibition of human immunodeficiency virus type 1 transcription and replication by DNA sequence-selective plant lignans.

A plant lignan, 3'-O-methyl nordihydroguaiaretic acid (3'-O-methyl NDGA, denoted Malachi 4:5-6 or Mal.4; molecular weigth 316), was isolated from Larrea tridentata and found to be able to inhibit human immunodeficiency virus (HIV) Tat-regulated transactivation in vivo, induce protection of lymphoblastoid CEM-SS cells from HIV (strain IIIB) killing, and suppress the replication of five HIV-1 strains (WM, MN, VS, JR-CSF, and IIIB) in mitogen-stimulated peripheral blood mononuclear cells, all in a dose-dependent manner. Mal.4 inhibits both basal transcription and Tat-regulated transactivation in vitro. The target of Mal.4 has been localized to nucleotides -87 to -40 of the HIV long terminal repeat. Mal.4 directly and specifically interferes with the binding of Sp1 to Sp1 sites in the HIV long terminal repeat. By inhibiting proviral expression, Mal.4 may be able to interrupt the life cycles of both wild-type and reverse transcriptase or protease mutant viruses in HIV-infected patients.

Animals↗

Towards eliminating lymphatic filariasis in Papua New Guinea: impact of annual single-dose mass treatment on transmission of Wuchereria bancrofti in East Sepik Province.

The impact of annual single-dose community-wide treatment on the transmission of Wuchereria bancrofti was investigated in 5 villages in the East Sepik Province where pretreatment prevalence of microfilaraemia ranged from 34% to 73%. Anopheles punctulatus and An. koliensis were the only carriers of the parasite. 3 villages received diethylcarbamazine citrate (DEC) in combination with ivermectin (IVR) and 2 received DEC alone. The rate and intensity of microfilaraemia were both reduced in all 5 villages. Reduction in prevalence was between 43% and 67% in the DEC+IVR study villages and between 24% and 27% in the DEC alone villages. Density was reduced by between 81% and 95% in the DEC+IVR villages and between 69% and 74% in the DEC alone villages. Breaks in perennial transmission (failure to detect infective mosquitoes in four or more consecutive monthly collections) occurred in all 3 communities treated with DEC+IVR. Transmission was almost completely interrupted in 2 villages, where infective mosquitoes were not detected during 11 of the 12 months following treatment. We concluded that repeated annual single-dose community-wide treatment with DEC+IVR could lead to complete interruption of transmission and ultimately elimination of lymphatic filariasis.

Animals↗

The coding region of the human c-mos pseudogene contains Alu repeat insertions.

We have determined the nucleotide sequence of an 841-bp fragment derived from a segment of the human genome previously cloned by Chumakov et al. [Gene 17 (1982) 19-26] and Zabarovsky et al. [Gene 23 (1983) 379-384] and containing regions homologous to the viral mos gene probe. This sequence displays homology with part of the coding region of the human and murine c-mos genes, contains several termination codons, and is interrupted by two Alu-family elements flanked by short direct repeats. Probably, the progenitor of the human c-mos gene was duplicated approximately at the time of mammalian divergence, was converted to a pseudogene, and acquired insertions of two Alu elements.

Base Sequence↗

Visceral protein increase associated with interrupt versus continuous enteral hyperalimentation.

Periodic parenteral hyperalimentation, the interruption of feeding for a period of time each day, parallels the fasted vs fed state in the meal eater. The fasted state appears to be more physiologic and seems to be associated with an increase of visceral proteins. Intravenous hyperalimentation data that have been published seem to confirm this fact. The purpose of this study was to compare the effect of continuous enteral hyperalimentation and interrupt enteral hyperalimentation on the visceral protein compartment. Two groups of 10 afebrile matched control patients (group 1) were on continuous enteral hyperalimentation for 19 +/- 6 days with no improvement in serum albumin or serum transferrin levels. No changes were made in the feeding schedules of 10 of the patients. Feeding schedules of the other 10 patients were changed to an 8-hr interrupt enteral hyperalimentation with calories, protein, and volume being provided remaining the same. Repeat serum albumin and transferrin levels were obtained after 10 days. There was a significant increase in albumin and transferrin levels (p less than 0.005) in those patients changed to an interrupt feeding schedule.

Adult↗