Southeast Asian Mitochondrial DNA Analysis Reveals Genetic Continuity of Ancient Mongoloid Migrations

Human mitochondrial DNAs (mtDNAs) from 153 independent samples encompassing seven Asian populations were surveyed for sequence variation using the polymerase chain reaction (PCR), restriction endonuclease analysis and oligonucleotide hybridization. All Asian populations were found to share two ancient AluI/DdeI polymorphisms at nps 10394 and 10397 and to be genetically similar indicating that they share a common ancestry. The greatest mtDNA diversity and the highest frequency of mtDNAs with HpaI/HincII morph 1 were observed in the Vietnamese suggesting a Southern Mongoloid origin of Asians. Remnants of the founding populations of Papua New Guinea (PNG) were found in Malaysia, and a marked frequency cline for the COII/tRNA(Lys) intergenic deletion was observed along coastal Asia. Phylogenetic analysis indicates that both insertion and deletion mutations in the COII/tRNA(Lys) region have occurred more than once.     

Hematopoietic stem cells in mice during embryonic development preceding the establishment of liver hematopoiesis]

We studied the time course of appearance of CFUs (7-8 days old) in embryos of (C57B1/6 x CBA)F1 mice from the 8th day of embryonic development. Significant amounts of CFUs could be detected from the 10th day of development, initially in the body of the embryo from the stage of 30-33 pairs of somites, then in the yolk sac and still later, from the stage of about 40 pairs of somites, in liver anlage. CFUs could not be reliably detected until the 9th day of development either in the embryo itself or in the yolk sac. However, after incubation of nine day old embryos for four days in organ culture, such cultures contained CFUs. CFUs could be found in significant levels in embryos explanted from the embryos at the stage no earlier than 24 pairs of somites. When the yolk sac and the embryo were cultivated separately, CFUs could also be detected, however, the removal of liver primordium from the embryo did not influence the amount of CFUs in its body. CFUs were not found in cultures of liver primordium from nine day old embryos. Thus, we can detect pre-CFUs in 9 day old embryos at the stage 25-28 pairs of somites using the system of organ culture; at the same time CFUs cannot be found in intact embryos of the same age. These data provide evidence that before the establishment of liver hemopoiesis precursors of CFUs are located both in the yolk sac and in the embryo outside rudimentary liver. However, our results do not provide any data for the conclusion about the primary source of pre-CFUs in the mouse embryo.     

Organization, structure, and polymorphisms of the human profilaggrin gene

Profilaggrin is a major protein component of the keratohyalin granules of mammalian epidermis. It is initially expressed as a large polyprotein precursor and is subsequently proteolytically processed into individual functional filaggrin molecules. We have isolated genomic DNA and cDNA clones encoding the 5'- and 3'-ends of the human gene and mRNA. The data reveal the presence of likely "CAT" and "TATA" sequences, an intron in the 5'-untranslated region, and several potential regulatory sequences. While all repeats are of the same length (972 bp, 324 amino acids), sequences display considerable variation (10-15%) between repeats on the same clone and between different clones. Most variations are attributable to single-base changes, but many also involve changes in charge. Thus, human filaggrin consists of a heterogeneous population of molecules of different sizes, charges, and sequences. However, amino acid sequences encoding the amino and carboxyl termini are more conserved, as are the 5' and 3' DNA sequences flanking the coding portions of the gene. The presence of unique restriction enzyme sites in these conserved flanking sequences has enabled calculations on the size of the full-length gene and the numbers of repeats in it: depending on the source of genomic DNA, the gene contains 10, 11, or 12 filaggrin repeats that segregate in kindred families by normal Mendelian genetic mechanisms. This means that the human profilaggrin gene system is also polymorphic with respect to size due to simple allelic differences between different individuals. The amino- and carboxyl-terminal sequences of profilaggrin contain partial or truncated repeats with unusual un-filaggrin-like sequences on the termini.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amerindian mitochondrial DNAs have rare Asian mutations at high frequencies, suggesting they derived from four primary maternal lineages.

The mitochondrial DNA (mtDNA) sequence variation of the South American Ticuna, the Central American Maya, and the North American Pima was analyzed by restriction-endonuclease digestion and oligonucleotide hybridization. The analysis revealed that Amerindian populations have high frequencies of mtDNAs containing the rare Asian RFLP HincII morph 6, a rare HaeIII site gain, and a unique AluI site gain. In addition, the Asian-specific deletion between the cytochrome c oxidase subunit II (COII) and tRNA(Lys) genes was also prevalent in both the Pima and the Maya. These data suggest that Amerindian mtDNAs derived from at least four primary maternal lineages, that new tribal-specific variants accumulated as these mtDNAs became distributed throughout the Americas, and that some genetic variation may have been lost when the progenitors of the Ticuna separated from the North and Central American populations.     

Salivary peroxidase,Pm, and Ph protein polymorphisms in Malaysians

Summary Three human saliva genetic markers, namely, salivary peroxidase (SAPX), Pm, and Ph proteins, were investigated in the three major ethnic groups of Malaysia: Malays, Chinese, and Indians.For Pm, the allelic frequencies of Pm ⁺ for Malays, Chinese, and Indians are 0.385±0.030, 0.282±0.026, and 0.289±0.026 respectively. For Ph, the allelic frequencies of Ph ⁺ are 0.082±0.016 for Malays, 0.109±0.017 for Chinese, and 0.062±0.013 for Indians. For SAPX, the allelic frequencies of SAPX ¹ in Malays, Chinese, and Indians are 0.762±0.027, 0.755±0.027, and 0.723±0.026 respectively.     

Terbium ion binding to Limuluspolyphemus hemocyanin

Terbium ion binds to calcium-free $\text{Limulus}$ hemocyanin at pH 7.0 and 8.9, and promotes the aggregation of hemocyanin subunits, a phenomenon associated with calcium binding. An excitation maximum for the bound terbium at 293 nm and the results of treating the hemocyanin with N-bromosuccinimide indicate that energy transfer from tryptophan to the bound terbium is responsible for the enhancement of terbium fluorescence. At pH 8.9, addition of calcium to hemocyanin containing bound terbium results in only a partial loss of terbium fluorescence, suggesting heterogeneity in the terbium binding sites. Titration of hemocyanin with terbium also indicates multiple binding sites.     

Myopia Development in Tree Shrew Is Associated with Chronic Inflammatory Reactions

In this study, we aimed to investigate whether chronic retinal inflammation is involved in the pathogenesis of form-deprivation myopia (FDM) using tree shrews as an animal model. Twenty-one tree shrews were randomly divided into 7-day/14-day FDM (FDM7/FDM14) groups and their corresponding 7-day/14-day control groups. Refraction and axial length were measured. To determine the effects of form deprivation on inflammation, we used real-time polymerase chain reaction (PCR) and immunohistochemistry to assess the expression levels of several proinflammatory cytokines. At day 0, the eyes in the FDM and control groups were hyperopic. However, after 7 and 14 days of form deprivation, the refractive error of the eyes in the FDM7 and FDM14 groups shifted from +6.6 ± 0.3 diopters (D) to +4.0 ± 0.5 D and from +6.4 ± 0.3 D to +5.0 ± 0.3 D, respectively. The levels of tumor necrosis factor-α, interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1, and nuclear factor κB were increased in the FDM eyes, compared with those in the control eyes. The increase in matrix metalloproteinase-2 expression was greater in the FDM eyes than in the contralateral and control eyes, whereas collagen type I expression was downregulated. In conclusion, chronic inflammation may play a crucial pathogenic role in form-deprivation myopia in tree shrews.     

Development and evaluation of an efficient and real-time monitoring system for the vector mosquitoes,Aedes albopictus and Culex quinquefasciatus

BackgroundThe surveillance of vector mosquitoes is essential for prevention and control of mosquito-borne diseases. In this study, we developed an internet-based vector mosquito monitor, MS-300, and evaluated its efficiency for the capture of the important vector mosquitoes, Aedes albopictus and Culex quinquefasciatus, in laboratory and field trials.Methodology/Principal findingsThe linear sizes of adult Ae. albopictus and Cx. quinquefasciatus were measured and an infrared window was designed based on these data. A device to specifically attract these two species and automatically transmit the number of captured mosquitoes to the internet was developed. The efficiency of the device in capturing the two species was tested in laboratory, semi-field and open field trials. The efficiency results for MS-300 for catching and identifying Ae. albopictus in laboratory mosquito-net cages were 98.5% and 99.3%, and 95.8% and 98.6%, respectively, for Cx. quinquefasciatus. In a wire-gauze screened house in semi-field trials, the efficiencies of MS-300 baited with a lure in catching Ae. albopictus and Cx. quinquefasciatus were 54.2% and 51.3%, respectively, which were significantly higher than 4% and 4.2% without the lure. The real-time monitoring data revealed two daily activity peaks for Ae. albopictus (8:00–10:00 and 17:00–19:00), and one peak for Cx. quinquefasciatus (20:00–24:00). During a 98-day surveillance trial in the field, totals of 1,118 Ae. albopictus and 2,302 Cx. quinquefasciatus were captured by MS-300. There is a close correlation between the number of captured mosquitoes and the temperature in the field, and a positive correlation in the species composition of the captured samples among the mosquitoes using MS-300, BioGents Sentinel traps and human landing catches.Conclusions/SignificanceThe data support the conclusion that MS-300 can specifically and efficiently capture Ae. albopictus and Cx. quinquefasciatus, and monitor their density automatically in real-time. Therefore, MS-300 has potential for use as a surveillance tool for prevention and control of vector mosquitoes.     

α-肿瘤坏死因子的肿瘤靶向性改造

α-肿瘤坏死因子(tumor necrosis factor-α,TNF-α)是一种多效性的细胞因子,能高效地杀伤或抑制肿瘤细胞。但是由于其对全身有毒副作用,这使T N F-α的应用受到了限制。提高T N F-α的抗肿瘤活性,降低毒副作用以及开发具有肿瘤靶向性的融合蛋白是将其应用于临床的关键。     

Cystine Deprivation Induces Oligodendroglial Death: Rescue by Free Radical Scavengers and by a Diffusible Glial Factor

Abstract: In this study we examined the effect on oligodendroglial survival of exogenous cystine deprivation. Oligodendroglia isolated from mixed glial primary cultures derived from brains of 1-day-old rats, and then grown for 3 days, were markedly dependent on extracellular cystine for survival. The EC₅₀ values for cystine for a 24-h exposure ranged from 2 to 65 µ M . After 6 h of cystine deprivation, the cellular glutathione level decreased to 21 ± 13% of the control. Free radical scavengers (α-tocopherol, ascorbate, idebenone, and N-tert -butyl-α-phenylnitrone) were protective against cystine deprivation but had no effect on the glutathione level. An iron chelator, desferrioxamine mesylate, also was protective. These findings suggest that intracellular hydroxyl radicals are important for this toxicity. In contrast to the observations in 3-day-old cultures, the dependence on exogenous cystine for cell viability was not observed consistently in oligodendroglia cultured for 6 days before the onset of cystine deprivation. Several observations suggested that this loss of cystine dependence was due to a diffusible factor. Sensitivity to the toxicity of cystine deprivation in day 6 cultures increased as the volume of medium was increased from 0.3 to 2 ml. Furthermore, preincubation of cystine-depleted medium with astrocyte cultures eliminated the toxicity of the cystine deprivation. HPLC assay of the conditioned cystine-depleted medium showed no significant change in cystine or cysteine concentration. We conclude that oligodendroglia are highly susceptible to cystine deprivation in day 3 cultures and that this susceptibility is due to the accumulation of intracellular free radicals in the setting of glutathione depletion. The resistance of day 6 oligodendroglial cultures is caused at least in part by a diffusible factor.