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T H Le

Publications and source records attributed to T H Le.

At least 19 recordsLinked to original sources
PubMed2003

The phylogeny of the Schistosomatidae based on three genes with emphasis on the interrelationships of Schistosoma Weinland, 1858.

Schistosomes are digenean flukes, parasitic of birds, mammals and crocodiles. The family Schistosomatidae contains species of considerable medical and veterinary importance, which cause the disease schistosomiasis. Previous studies, both morphological and molecular, which have provided a good deal of information on the phylogenetics of this group, have been limited in the number of species investigated or the type or extent of molecular data used. This paper presents the most comprehensive phylogeny to date, based on the sequences of 3 genes, complete ribosomal small subunit rRNA and large ribosomal subunit rRNA, and mitochondrial cytochrome oxidase 1, sequenced from 30 taxa including at least 1 representative from 10 of the 13 known genera of the Schistosomatidae and 17 of the 20 recognized Schistosoma species. The phylogeny is examined using morphological characters, intermediate and definitive host associations and biogeography. Theories as to the origins and spread of Schistosoma are also explored. The principal findings are that Ornithobilharzia and Austrobilharzia form a sister group to the Schistosoma; mammalian schistosomes appear paraphyletic and 2 Trichobilharzia species, T. ocellata and T. szidati, seem to be synonymous. The position of Orientobilharzia within the Schistosoma is confirmed, as is an Asian origin for the Schistosoma, followed by subsequent dispersal through India and Africa.

Animals↗
PubMed2002

Complete mitochondrial genomes confirm the distinctiveness of the horse-dog and sheep-dog strains of Echinococcus granulosus.

Unlike other members of the genus, Echinococcus granulosus is known to exhibit considerable levels of variation in biology, physiology and molecular genetics. Indeed, some of the taxa regarded as 'genotypes' within E. granulosus might be sufficiently distinct as to merit specific status. Here, complete mitochondrial genomes are presented of 2 genotypes of E. granulosus (G1-sheep-dog strain: G4-horse-dog strain) and of another taeniid cestode, Taenia crassiceps. These genomes are characterized and compared with those of Echinococcus multilocularis and Hymenolepis diminuta. Genomes of all the species are very similar in structure, length and base-composition. Pairwise comparisons of concatenated protein-coding genes indicate that the G1 and G4 genotypes of E. granulosus are almost as distant from each other as each is from a distinct species, E. multilocularis. Sequences for the variable genes atp6 and nad3 were obtained from additional genotypes of E. granulosus, from E. vogeli and E. oligarthrus. Again, pairwise comparisons showed the distinctiveness of the G1 and G4 genotypes. Phylogenetic analyses of concatenated atp6, nad1 (partial) and cox1 (partial) genes from E. multilocularis, E. vogeli, E. oligarthrus, 5 genotypes of E. granulosus, and using T. crassiceps as an outgroup, yielded the same results. We conclude that the sheep-dog and horse-dog strains of E. granulosus should be regarded as distinct at the specific level.

Amino Acid Sequence↗
PubMed2002

Revisiting the question of limited genetic variation within Schistosoma japonicum.

Recent electrophoretic data have indicated that Schistosoma japonicum in mainland China may be a species complex, with the existence of a cryptic species being predicted from the analysis of schistosome populations from Sichuan province. To investigate the Sichuan form of S. japonicum, 4.9 kbp of mitochondrial DNA from each of three samples of the parasite from China (two from Sichuan and one from Hunan) and one from Sorsogon in the Philippines were amplified, sequenced and characterized. The sequence data were compared with those from the related South-east Asian species of S. mekongi (Khong Island, Laos) and S. mlayensis (Baling, Malaysia) and that from S. japonicm from Anhui (China). At both the nucleotide and amino-acid levels, the variation among the five S. japonicum samples was limited (< 1%). This was consistent with the conclusions drawn from previous molecular studies, in which minimal variation among S. japonicum populations was also detected. In contrast, S. mekongi and S. malayensis, species recognized as separate but closely related, differ from each other by about 10%, and each differs by 25%-26% from S. japonicum. Phylogenetic trees provided a graphic representation of these differences, showing all S. japonicum sequences to be very tightly clustered and distant from S. mekongi and S. malayensis, the last two being clearly distinct from each other. The results thus indicate no significant intra-specific genetic variation among S. japonicum samples collected from different geographical areas and do not support the idea of a distinct form in Sichuan.

Amino Acid Sequence↗
PubMed2001

Mitochondrial gene content, arrangement and composition compared in African and Asian schistosomes.

Complete sequences were obtained for the coding portions of the mitochondrial (mt) genomes of Schistosoma mansoni (NMRI strain, Puerto Rico; 14 415 bp), S. japonicum (Anhui strain, China; 14 085 bp) and S. mekongi (Khong Island, Laos; 14 072 bp). Each comprises 36 genes: 12 protein-encoding genes (cox1-3, nad1-6, nad4L, atp6 and cob); two ribosomal RNAs, rrnL (large subunit rRNA or 16S) and rrnS (small subunit rRNA or 12S); as well as 22 transfer RNA (tRNA) genes. The atp8 gene is absent. A large segment (9.6 kb) of the coding region (comprising 14 tRNAs, eight complete and two incomplete protein-encoding genes) for S. malayensis (Baling, Malaysian Peninsula) was also obtained. Each genome also possesses a long non-coding region that is divided into two parts (a small and a large non-coding region, the latter not fully sequenced in any species) by one or more tRNAs. The protein-encoding genes are similar in size, composition and codon usage in all species except for cox1 in S. mansoni (609 aa) and cox2 in S. mekongi (219 aa), both of which are longer than homologues in other species. An unexpected finding in all the Schistosoma species was the presence of a leucine zipper motif in the nad4L gene. The gene order in S. mansoni is strikingly different from that seen in the S. japonicum group and other flatworms. There is a high level of identity (87-94% at both the nucleotide and amino acid levels) for all protein-encoding genes of S. mekongi and S. malayensis. The identity between genes of these two species and those of S. japonicum is less (56-83% for amino acids and 73-79% for nucleotides). The identity between the genes of S. mansoni and the Asian schistosomes is far less (33-66% for amino acids and 54-68% for nucleotides), an observation consistent with the known phylogenetic distance between S. mansoni and the other species.

Africa↗
PubMed2001

A leucine zipper protein of mitochondrial origin.

Sequence-specific DNA-binding proteins are characterised by short coiled-coil structural domains classified as zinc finger/RING finger, leucine zipper (L-Zip) or helix-loop-helix (HLH) motifs. The L-Zip proteins are defined by a pattern of at least four leucine (L) residues repeated every seventh amino acid that mediates protein dimerisation through the formation of parallel alpha-helical dimers. Usually the zipper is incorporated into a helix-loop-helix conformation called the basic helix-loop-helix-leucine zipper (bHLH/Zip). To date, all of the several hundred proteins reported as containing the L-Zip and/or bHLH/Zip motifs are nuclear-encoded. No leucine zipper polypeptide has, hitherto, been reported as mitochondrial in origin. Here we report such a polypeptide, the nicotinamide dehydrogenase subunit 4L (nad4L). We first identified this in human blood flukes of the genus Schistosoma (phylum Platyhelminthes; class Trematoda) but show that this is a common feature in other eucaryotes as well. Therefore, in addition to their well recognised role in oxidative phosphorylation, nad4L proteins may be pivotally involved in a range of other biological processes such as transcription and/or replication activation or as signal transmitters in communication with the nucleus and other cellular organelles. This may indicate a link between transcription regulation and respiration in mitochondria. We have also identified L-Zip-like motifs in nuoK, the procaryotic equivalent of the nad4L mitochondrial protein.

Amino Acid Sequence↗
PubMed2001

Functional MRI of human auditory cortex using block and event-related designs.

fMRI of human auditory cortex response to sinusoidal tones of 200, 1000, and 3000 Hz was evaluated using block design and conventional and "silent" event-related designs. Conventional event-related fMRI revealed the timecourse of the BOLD response (approximately 5 sec to peak, approximately 4 sec full-width-half-max, and approximately 14 sec recovery to baseline). Both event-related, but not block, designs provided evidence for tonotopic organization in auditory cortex. Sources of low-frequency activation were more lateral and anterior than the sources of high-frequency activation (P < or = 0.05). In the block designs, repeated rapid stimulus presentation and the co-incidence of scanner noise preclude definition of tonotopic organization revealed in event-related approaches. Magn Reson Med 45:254-260, 2001.

Acoustic Stimulation↗
PubMed2001

Complete DNA sequence and gene organization of the mitochondrial genome of the liverfluke, Fasciola hepatica L. (Platyhelminthes; Trematoda).

The complete nucleotide sequence of the mitochondrial (mt) DNA molecule of the liverfluke, Fasciola hepatica (phylum Platyhelminthes, class Trematoda, family Fasciolidae), was determined. It comprises 14462 bp, contains 12 protein-encoding, 2 ribosomal and 22 transfer RNA genes, and is the second complete flatworm (and the first trematode) mitochondrial sequence to be described in detail. All of the genes are transcribed from the same strand. Of the genes typically found in mitochondrial genomes of eumetazoans, only atp8 is absent. The nad4L and nad4 genes overlap by 40 nt. Most intergenic sequences are very short. Two larger non-coding regions are present. The longer one (817 nt) is located between trnG and cox3 and consists of 8 identical tandem repeats of 85 nt, rich in G and C, followed by 1 imperfect repeat. The shorter non-coding region (187 nt) exhibits no special features and is separated from the longer region by trnG. The gene arrangement resembles that of some other trematodes including the eastern Asian Schistosoma species (and cyclophyllidean cestode species) but it is strikingly different from that of the African schistosomes, represented by Schistosoma mansoni. The genetic code is as inferred previously for flatworms. Transfer RNA genes range in length from 58 to 70 nt, their products producing characteristic 'clover leaf' structures, except for tRNA(S(UNC)) and tRNA(S(AGN)) lacking the DHU arm.

Animals↗
PubMed2001

Molecular analysis of beta-thalassemia in South Vietnam.

The high prevalence of beta-thalassemia in Southeast Asia is a major public health problem. Development of genetic counseling and prenatal diagnosis programs is a priority. To provide the groundwork for such programs in South Vietnam, we determined the spectrum of beta-thalassemia mutations in 35 severely affected patients and their relatives. We identified six different beta-thalassemia alleles (five beta(0) and one beta(+) mutations), in addition to the common mutation at codon 26 (GAG --> AAG) responsible for Hb E. These data provide insights into the distribution of beta-thalassemia alleles in the Vietnamese population.

Alleles↗
PubMed2000

Mitochondrial genomes of human helminths and their use as markers in population genetics and phylogeny.

To date, over 100 complete metazoan mitochondrial (mt) genomes of different phyla have been reported. Here, we briefly summarise mt gene organisation in the Metazoa and review what is known of the mt genomes of nematodes and flatworms parasitic in humans. The availability of complete or almost complete mtDNA sequences for several parasitic helminths provides a rich source of genetic markers for phylogenetic analysis and study of genetic variability in helminth groups. Examples of the application of mtDNA in studies on Ascaris, Onchocerca, Schistosoma, Fasciola, Paragonimus, Echinostoma, Echinococcus and Taenia are described.

Animals↗
PubMed2000

What can knockout mice contribute to an understanding of hypertension?

The generation of knockout mice using homologous recombination in embryonic stem cells is a powerful tool for physiologic investigations. This experimental approach has provided unique insights into the study of hypertension. Studies using knockout mice have shed new light on blood pressure regulatory mechanisms, molecular mechanisms of end-organ injury, and genetic mechanisms for hypertension. With the development of more accessible approaches for carrying out sophisticated manipulation of the mouse genome, there will be continuing utility of this technique for future studies of hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Mitochondrial DNA sequences of human schistosomes: the current status.

Sequences generated from the mitochondrial genome provide useful molecular markers for defining population groups, for tracing the genetic history of an individual or a particular group of related individuals, and for constructing deep-branch taxonomic phylogenies. There is every reason to believe that the mitochondrial genome will be as valuable in studies on flatworms, such as the human schistosomes, as it has been for other taxa. To date, however, our knowledge of mitochondrial genomes of flatworms remains limited, and this review summarises the currently available information. In particular, details of the recent sequence obtained for cloned Schistosoma mansoni mitochondrial DNA fragments spanning over half of the mitochondrial genome of this species are emphasised. This and other information, available as a result of the Schistosome Genome Project, provide the basis for obtaining the complete mitochondrial DNA sequence and gene order of S. mansoni and the other human schistosomes. The availability of complete mitochondrial DNA sequences from the different species will facilitate much more in-depth study of genetic diversity and host specificity in schistosomes and the interrelationships between the various forms infecting humans and between these and other flatworms.

Animals↗
PubMed2000

Application of micellar electrokinetic chromatography for the separation of retinoids.

The applicability of micellar electrokinetic chromatography (MEKC) using sodium dodecylsulphate (SDS) as pseudo-stationary phase for the separation of five retinoids (retinol, retinal, retinyl acetate, retinyl palmitate, retinoic acid), was investigated. The effects of the acetonitrile content, the SDS concentration, the pH and the addition of Brij 35 to the background electrolyte on the migration behaviour of the retinoids were determined. It was found that the effective mobilities of retinol, retinal and retinyl acetate could be easily regulated through the ACN content and the SDS concentration of the BGE. The electrophoretic behaviour of the very hydrophobic retinyl palmitate was abnormal. Under various conditions this compound showed up as a late, very sharp peak. A strong indication was found that the retinyl palmitate forms a stable, charged complex with SDS during sample preparation. The mobility of the retinyl palmitate peak could be regulated, independently from the other peaks, through the Brij concentration of the BGE. Using a running buffer consisting of Tris buffer (pH 8), 20 mmol l(-1) SDS, 1 mmol l(-1) Brij 35 and 35% (v/v) acetonitrile, a complete separation of the five retinoids could be realised in less than 20 min.

Acetonitriles↗
PubMed1999

Further evaluation of the initial negative response in functional magnetic resonance imaging.

The initial negative response (i.e., the dip) in the functional MR signal at stimulus onset has aroused much interest. Such a response is consistent with optical imaging data and can be potentially mapped to generate spatially more specific maps. However, there are still controversies regarding the exact origin of the initial response. In particular, experimental reports of its echo-time dependence have been inconsistent. Furthermore, several investigators have suggested the possibility of an apparent dip that may arise artifactually when the interstimulus interval (ISI) is not sufficiently long. The present study investigates the echo-time dependence of the initial response and the effect of the ISI on the initial response. Experimental results obtained at TEs of 21, 30, and 45 msec demonstrate that the initial dip has a TE dependence that is in agreement with a T2* contrast, and thereby consistent with a blood oxygenation level-dependent origin. At an ISI of 90 sec, a statistically significant initial negative response was detected and shown to be indistinguishable from that observed at an ISI of 45 sec, which was used in our previous studies, indicating that the initial negative response observed at 4 T is not a consequence of short ISI.

Echo-Planar Imaging↗
PubMed1999

Mitochondrial genes of Schistosoma mansoni.

Two clones, totalling 8068 bp and spanning over half of the coding region of the mitochondrial genome of Schistosoma mansoni, have been sequenced. Complete sequences are presented of the large and small ribosomal RNA subunits, CO2, ND3, ND4, ND6 and ATPase 6 genes. Incomplete sequences were found for the CO1, ND2 and CytB genes. At least 10 tRNAs were also detected and alternative structures for some of these discussed. The gene order of S. mansoni is unique and differs from that of Fasciola hepatica, the only other trematode for which any information is available.

Amino Acid Sequence↗