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Biomedical subjects

Z Tu

Publications and source records attributed to Z Tu.

At least 19 recordsLinked to original sources

Transposable element (TE) display and rapid detection of TE insertion polymorphism in the Anopheles gambiae species complex.

Transposable element (TE) display was shown to be a highly specific and reproducible method of detecting the insertion sites of TEs in individuals of the African malaria mosquito, Anopheles gambiae, and its sibling species, A. arabiensis. Relatively high levels of insertion polymorphism were observed during the TE display of several families of miniature inverted-repeat TEs (MITEs) that have variable copy numbers. The genomic locations of selected insertion sites were identified by matching the sequences of their corresponding bands in a TE display gel to specific regions of the draft A. gambiae genome assembly. We discuss different scenarios in which TE display will provide powerful dominant and co-dominant genetic markers to study the behaviour of TEs in A. gambiae populations and to illustrate the complex population genetics of this intriguing disease vector. We suggest that TE display can also provide tools for a phylogenetic analysis of the A. gambiae complex.

Animals↗

Chromaproline and Chromaperidine, nicotine agonists, and Donepezil, cholinesterase inhibitor, enhance performance of memory tasks in ovariectomized rats.

Chromaproline and Chromaperidine, two recently synthesized and pharmacologically characterized nicotinic agonists, and Donepezil (Aricept), an acetylcholinesterase inhibitor approved for the treatment of memory loss, were evaluated for effects on performance of a visual recognition memory task (object recognition) and a spatial memory task (object placement). Ovariectomized female rats received the drugs chronically via subcutaneous Alzet minipumps. None of the drugs altered activity in the open field or the time spent exploring objects in the field. One week following initiation of treatment, all three drugs enhanced performance of the visual recognition task, but only Donepezil enhanced performance of the spatial memory task. With a longer period of treatment (3 weeks), the nicotinic agonist Chromaproline also enhanced object placement performance. Current results show the memory-enhancing efficacy of Donepezil in two additional memory tasks in rats and suggest that the novel nicotinic agonists, Chromaproline and Chromaperidine, may also be useful new drugs for the treatment of memory impairments/loss.

Animals↗

2-(2-Piperidyl)- and 2-(2-pyrrolidyl)chromans as nicotine agonists: synthesis and preliminary pharmacological characterization.

As part of an effort to develop a new class of subtype selective nicotine agonists, we have synthesized and tested a group of 12 hydroxylated 2-(2-piperidyl)- and 2-(2-pyrrolidyl)chromans. In rat brain membranes, all 12 compounds displayed poor affinity for [(125)I]-alpha-bunagarotoxin binding sites. In contrast, three compounds, 17c, 24, and 26, displayed moderate to high affinity for [(3)H]cytisine binding sites, while three (17b, 18b,c) and six (17a,d,e and 18a,d,e) compounds showed weak and poor affinity, respectively, for these same sites. In subsequent studies, compounds 17a and 17c were found to stimulate the efflux of (86)Rb(+) from rat cortical synaptosomes, an indication of agonist activity. Further, both 17c and 26 displayed high intrinsic activity in stimulating the release of [(3)H]dopamine from striatal synaptosomes; however, only 17c was effective at stimulating the release of [(3)H]acetylcholine from cortical synaptosomes, suggesting differential selectivity. In cloned human nicotinic acetylcholine receptors (nAChR) expressed in Xenopus oocytes, both 17c and 26 activated alpha7 and alpha3beta2 receptor subtypes in a dose-dependent manner, but 26 was clearly the more potent agonist. Last, neither compound displayed dose-dependent activation of alpha4beta2 nAChRs. We conclude that 2-(2-azacyclic)chromans appear to be a promising new class of nicotine agonists.

Acetylcholine↗

Embryonic and hematopoietic stem cells express a novel SH2-containing inositol 5'-phosphatase isoform that partners with the Grb2 adapter protein.

SH2-containing inositol 5'-phosphatase (SHIP) modulates the activation of immune cells after recruitment to the membrane by Shc and the cytoplasmic tails of receptors. A novel SHIP isoform of approximately 104 kd expressed in primitive stem cell populations (s-SHIP) is described. It was found that s-SHIP is expressed in totipotent embryonic stem cells to the exclusion of the 145-kd SHIP isoform expressed in differentiated hematopoietic cells. s-SHIP is also expressed in primitive hematopoietic stem cells, but not in lineage-committed hematopoietic cells. In embryonic stem cells, s-SHIP partners with the adapter protein Grb2 without tyrosine phosphorylation and is present constitutively at the cell membrane. It is postulated that s-SHIP modulates the activation threshold of primitive stem cell populations.

Adaptor Proteins, Signal Transducing↗

I kappa B kinase is critical for TNF-alpha-induced VCAM1 gene expression in renal tubular epithelial cells.

The expression of VCAM1 is up-regulated in renal proximal tubular epithelial cells (TEC) in a variety of inflammatory renal diseases, a prominent example of which is acute renal allograft rejection. VCAM1 may play an important role in these diseases because it binds to the integrins very late Ag-4 and alpha(4)beta(7) on lymphocytes and monocytes, thereby providing a potential mechanism to recruit these leukocytes to sites of inflammation. The molecular mechanisms underlying VCAM1 regulation in renal TEC are essentially unknown. We now report that VCAM1 mRNA is dramatically up-regulated in C1, a cell line derived from renal TEC, on exposure to TNF-alpha. Two NF-kappaB binding sites in the VCAM1 promoter are critical for the TNF-alpha-induced VCAM1 transcriptional up-regulation, and both sites bind to p65-p50 NF-kappaB complexes. TNF-alpha induces activation of inhibitor of NF-kappaB (IkappaB) kinase-beta (IKK-beta), a protein kinase that phosphorylates the NF-kappaB inhibitor IkappaB, and thereby targets the latter for degradation via the ubiquitin-proteasome pathway. Moreover, dominant negative versions of IKK inhibit TNF-alpha activation of a VCAM1 promoter reporter. We conclude that the IKK/NF-kappaB pathway is critical in the TNF-alpha-induced up-regulation of VCAM1 mRNA in renal TEC.

Animals↗

Eight novel families of miniature inverted repeat transposable elements in the African malaria mosquito, Anopheles gambiae.

Eight novel families of miniature inverted repeat transposable elements (MITEs) were discovered in the African malaria mosquito, Anopheles gambiae, by using new software designed to rapidly identify MITE-like sequences based on their structural characteristics. Divergent subfamilies have been found in two families. Past mobility was demonstrated by evidence of MITE insertions that resulted in the duplication of specific TA, TAA, or 8-bp targets. Some of these MITEs share the same target duplications and similar terminal sequences with MITEs and other DNA transposons in human and other organisms. MITEs in A. gambiae range from 40 to 1340 copies per genome, much less abundant than MITEs in the yellow fever mosquito, Aedes aegypti. Statistical analyses suggest that most A. gambiae MITEs are in highly AT-rich regions, many of which are closely associated with each other. The analyses of these novel MITEs underscored interesting questions regarding their diversity, origin, evolution, and relationships to the host genomes. The discovery of diverse families of MITEs in A. gambiae has important practical implications in light of current efforts to control malaria by replacing vector mosquitoes with genetically modified refractory mosquitoes. Finally, the systematic approach to rapidly identify novel MITEs should have broad applications for the analysis of the ever-growing sequence databases of a wide range of organisms.

Africa↗

Maque, a family of extremely short interspersed repetitive elements: characterization, possible mechanism of transposition, and evolutionary implications.

Database analysis revealed a novel family of very short interspersed repetitive elements named Maque in the African malaria mosquito, Anopheles gambiae. Past mobility of Maque was demonstrated by evidence of its insertion that resulted in a target duplication. Approximately 220 copies of Maque were present in the A. gambiae genome. Although only approximately 60 bp long, Maque has the appearance of a distinct transposition unit. Eleven of the 12 Maque elements found in the database were flanked by 9-14 bp direct repeats, indicating that their transposition was relatively recent. Sequence comparison and phylogenetic analyses suggest that there are at least two subgroups within the Maque family, suggesting that they may have been originated from more than one source. Five of the 12 Maque elements had at least one other repetitive element nearby. Three of the Maque elements were found near genes. However, Maque was not found in the coding regions of genes or in any of the expressed sequence tags (ESTs), which is consistent with its significantly biased distribution toward A + T rich regions. Several characteristics of Maque indicate that it is likely a non-autonomous retro-element. The evolutionary origin of Maque and the differences between Maque and other known retro-elements including short interspersed repetitive elements (SINEs) are discussed. A hypothesis is proposed in which short sequences containing just the reverse transcriptase recognition signal (RTRS) could potentially contribute to exon shuffling and the genesis of some primordial SINEs.

Animals↗

MsqTc3, a Tc3-like transposon in the yellow fever mosquito Aedes aegypti.

A novel transposon, MsqTc3-Aa, has been discovered in the yellow fever mosquito, Aedes aegypti. Evidence of its past mobility is presented. There are approximately 100 copies of MsqTc3-Aa in A. aegypti, eight of which have been isolated and sequenced. All sequenced copies are more than 99% identical to their consensus, indicating recent mobilization. The MsqTc3-Aa consensus contains imperfect terminal inverted repeats (TIRs) and an open reading frame (ORF) interrupted by an intron. Sequence, structural and phylogenetic analysis showed that MsqTc3-Aa is a distant relative of Tc3, an active transposon in Caenorhabditis elegans. These results may provide useful information for the current effort to control mosquito-borne diseases using genetic approaches.

Aedes↗

Expanding the diversity of the IS630-Tc1-mariner superfamily: discovery of a unique DD37E transposon and reclassification of the DD37D and DD39D transposons.

A novel transposon named ITmD37E was discovered in a wide range of mosquito species. Sequence analysis of multiple copies in three Aedes species showed similar terminal inverted repeats and common putative TA target site duplications. The ITmD37E transposases contain a conserved DD37E catalytic motif, which is unique among reported transposons of the IS630-Tc1-mariner superfamily. Sequence comparisons and phylogenetic analyses suggest that ITmD37E forms a novel family distinct from the widely distributed Tc1 (DD34E), mariner (DD34D), and pogo (DDxD) families in the IS630-Tc1-mariner superfamily. The inclusion in the phylogenetic analysis of recently reported transposons and transposons uncovered in our database survey provided revisions to previous classifications and identified two additional families, ITmD37D and ITmD39D, which contain DD37D and DD39D motifs, respectively. The above expansion and reorganization may open the doors to the discovery of related transposons in a broad range of organisms and help illustrate the evolution and structure-function relationships among these distinct transposases in the IS630-Tc1-mariner superfamily. The presence of intact open reading frames and highly similar copies in some of the newly characterized transposons suggests recent transposition. Studies of these novel families may add to the limited repertoire of transgenesis and mutagenesis tools for a wide range of organisms, including the medically important mosquitoes.

Amino Acid Motifs↗

Possible horizontal transfer of a transposable element from host to parasitoid.

Full-length mariner-like elements (MLEs) were identified from both a parasitoid wasp, Ascogaster reticulatus, and its moth host, Adoxophyes honmai. MLEs were detected in two related Tortricid moths, but not in another Ascogaster species. The MLEs of A. reticulatus and A. honmai were 97.6% identical in DNA sequence. This high similarity suggests a recent horizontal transfer, probably from the moth host to the wasp parasitoid, facilitated by the intimacy of the host-parasitoid relationship.

Amino Acid Sequence↗

[Surgical treatment of great vessel injuries of thoracic outlet].

OBJECTIVE: To summarize the experience in surgical treatment of great vessel injury of the thoracic outlet. METHODS: Thirty-two cases (24 men and 8 women aged 2-48 years) treated by surgery were collected during the period of 1970-1998. Sharp injury, blunt injury or decelerated injury was the causes. The vessels of injury included the common carotid artery, subclavian artery and accompanying veins. Emergency suture or repair of the artery with polyester patch was performed in 15 patients, aneurysmectomy in 6, resection of vessels with end-to-end anastomosis in 5, Gore-Tex vessel reconstruction in 2, and transplantation of the great saphenous vein in 3. RESULTS: Twenty-four patients (75%) were cared and 7 (21.8%) died. CONCLUSIONS: In the early period, patients with great vessel injury of the thoracic outlet died from acute bleeding, cerebral ischemia or combined multiple injuries, in the later period, however, false aneurysm develop. The operation is appropriate to the recondition of damaged cut, the effect of evolution in false aneurysm is approving. For large damaged cut or for bigger vessel injuries, the repair with polyester patch, Gore-Tex of blood vessel reconstruction or the transplantation of the great saphenous vein must be used.

Adolescent↗

Colon interposition.

In the anatomy of the colon vasculature, the ascending branch of the left colic artery is the primary supplying vessel (96.91%). Isoperistaltic transposition of the transverse colon is preferred (83.58%). Riolan's vascular arcade is not a major vessel of the colon. It can only be found in less than 10% of patients, and whether or not this arcade is complete cannot be used as criterion to judge colon blood supply. Animal experiments and clinical studies have confirmed the superiority of one-layer over two-layer anastomosis. The former is simpler, safer, and more reliable, with a lower incidence of anastomotic leak or stricture. Based on a comprehensive evaluation of the disease type, patient age, heart and lung functions, nutritional status, and accompanying diseases, three colon transposition routes are available (anterosternal subcutaneous tunnel, retrosternal tunnel, and esophageal bed passage). The advantages and disadvantages of each route are analyzed, and the left-middle-left retrosternal route is described. The indications for esophageal reconstruction with colon operation (ERC) were collected and verified, increasing the number of indications to seven categories of diseases. The main complications of ERC, i.e., colon segment necrosis, anastomotic leak, recurrent laryngeal nerve injury, and intestinal obstruction were systematically studied, and their causes and prevention are detailed. The number of patients is the highest in a single unit among all the published reports. The incidence of complications and deaths are the lowest.

Adolescent↗

Synthesis and biological characterization of stable and radioiodinated (+/-)-trans-2-hydroxy-3-P[4-(3-iodophenyl)piperidyl]-1,2,3,4-tetrahydronaphthalene (3'-IBVM).

The vesamicol analogue (+/-)-trans-2-Hydroxy-3-[4-(3-iodophenyl)piperidyl]-1,2,3,4-tetrahydronaphthalene (3'-IBVM), a potent ligand for the vesicular acetylcholine transporter (VAChT), was evaluated as a potential radiotracer for studying VAChT density in vivo. In radioligand binding experiments, 3'-IBVM displays subnanomolar affinity for VAChT and 100-fold selectivity for VAChT over sigma1 and sigma2 receptors. Consistent with this profile, radioiodinated (+/-)-3'-IBVM distributed heterogenously in the rat brain following a bolus IV injection, displaying high concentrations in the striatum and moderate to low concentrations in the cortex and cerebellum, respectively. However, co-injection of the radiotracer with the sigma ligand haloperidol resulted in significant reductions of radiotracer levels in all brain regions examined. Therefore, radioiodinated (+/-)-IBVM appears to bind to both VAChT and sigma receptors in vivo.

Acetylcholine↗

Amplification of sequence tagged sites in five avian species using heterologous oligonucleotides.

Short of a complete genomic DNA sequence, sequence tagged sites (STSs) have emerged as major genomic reagents for the genetic analysis of little-studied ecologically and agriculturally important organisms. Here, we report STS developed for the turkey (Meleagris gallopavo), guinea fowl (Numidea meleagris), Japanese quail (Coturnix coturnix) and pigeon using primers specific for reference DNA sequences of two chicken (Gallus gallus) genes, aggrecan (agc1) and type X collagen (col10). Additional STSs were also developed for turkey, quail and chicken using primers specific for the human apobec-1 gene. The total length of the STSs developed was 5990, 2522, 4127, 1539 and 6600 bp for the turkey, guinea fowl, Japanese quail, pigeon and chicken, respectively. Based on splice site consensus GT and AG sequences, four of the seven agc1-based chicken STS appear to contain introns. The human gene-based STSs showed no significant sequence identity with the reference GenBank sequences. Maximum likelihood, maximum parsimony and neighbour-joining analysis of an agc1-based STS that was common to all five species showed phylogenetic relationships consistent with those previously defined using mitochondria DNA sequences and nuclear gene restriction maps. Additionally, several putative single nucleotide polymorphisms (SNPs) were detected within the STSs, including eight in the turkey, two in the quail, and two in the chicken when multiple sequences were evaluated from each species. This report describes new STSs that are resources for genetic and physical mapping and genome analysis within and among avian species. These resources should further aid in our understanding of the biology of agriculturally important but little-studied guinea fowl and turkey.

APOBEC-1 Deaminase↗

Molecular and evolutionary analysis of two divergent subfamilies of a novel miniature inverted repeat transposable element in the yellow fever mosquito, Aedes aegypti.

A novel family of miniature inverted repeat transposable elements (MITEs) named Pony was discovered in the yellow fever mosquito, Aedes aegypti. It has all the characteristics of MITEs, including terminal inverted repeats, no coding potential, A+T richness, small size, and the potential to form stable secondary structures. Past mobility of PONY: was indicated by the identification of two Pony insertions which resulted in the duplication of the TA dinucleotide targets. Two highly divergent subfamilies, A and B, were identified in A. aegypti based on sequence comparison and phylogenetic analysis of 38 elements. These subfamilies showed less than 62% sequence similarity. However, within each subfamily, most elements were highly conserved, and multiple subgroups could be identified, indicating recent amplifications from different source genes. Different scenarios are presented to explain the evolutionary history of these subfamilies. Both subfamilies share conserved terminal inverted repeats similar to those of the Tc2 DNA transposons in Caenorhabditis elegans, indicating that Pony may have been borrowing the transposition machinery from a Tc2-like transposon in mosquitoes. In addition to the terminal inverted repeats, full-length and partial subterminal repeats of a sequence motif TTGATTCAWATTCCGRACA represent the majority of the conservation between the two subfamilies, indicating that they may be important structural and/or functional components of the Pony elements. In contrast to known autonomous DNA transposons, both subfamilies of PONY: are highly reiterated in the A. aegypti genome (8,400 and 9, 900 copies, respectively). Together, they constitute approximately 1. 1% of the entire genome. Pony elements were frequently found near other transposable elements or in the noncoding regions of genes. The relative abundance of MITEs varies in eukaryotic genomes, which may have in part contributed to the different organizations of the genomes and reflect different types of interactions between the hosts and these widespread transposable elements.

Aedes↗

Recognition of sentences in noise by normal-hearing listeners using simulations of speak-type cochlear implant signal processors.

To assess whether more channels are needed to understand speech in noise than in quiet, we processed speech in a manner similar to that of spectral peak-like cochlear implant processors and presented it at a +2-dB signal-to-noise ratio to normal-hearing listeners for identification. The number of analysis filters varied from 8 to 16, and the number of maximum channel amplitudes selected in each cycle varied from 2 to 16. The results show that more channels are needed to understand speech in noise than in quiet, and that high levels of speech understanding can be achieved with 12 channels. Selecting more than 12 channel amplitudes out of 16 channels did not yield significant improvements in recognition performance.

Adult↗