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Multiple origins of Tibetan Y chromosomes.

The genetic origin of Tibetans was investigated using Y chromosome markers. A total of three populations were studied, two from central Tibet speaking central Tibetan and one from Yunnan speaking Kham. Two dominant paternal lineages (>80%) were identified in all three populations with one possibly from central Asia (YAP+) and the other from east Asia (M122C). We conclude that Tibetan Y chromosomes may have been derived from two different gene pools, given the virtual absence of M122C in central Asia and YAP+ in east Asia, with drift an unlikely mechanism accounting for these observations.

Alu Elements↗

Yfm1, a multicopy marker specific for the Y chromosome and beneficial for forensic, population, genetic, and spermatogenesis-related studies.

A recently developed microsatellite marker on the Y chromosome, Yfm1, which was originally cloned from a cosmid clone mapped near the DAZ (Deleted in AZoospermia) genes, was used to classify Y chromosomes using an automatic sequencer. Yfm1 could detect multicopies on Y chromosomes in a single polymerase chain reaction, showing four main classes, A, A*, B, and C, according to the number of copies and peak patterns. Compound haplotype analysis of the Y chromosome using the Yfm1 marker with three other biallelic markers on the Y chromosome, SRY, DXYS5Y, and YAP, resulted in nine different haplotypes among different populations, including Japanese. Haplotype II (defined by YAP insertion) observed in the Japanese population was consistently associated with Yfm1 class A or A*, which showed the lowest number of copies of Yfm1. Haplotypes III and IV were consistently associated with Yfm1 class B. On the other hand, haplotype I showed a variety of Yfm1 patterns that were dubbed class C when not appropriately classified as A, A*, or B. These relationships among Yfm1 microsatellite and Y-specific biallelic markers could supply useful population genetic information. Moreover, because we have already shown that men with haplotype II have significantly lower spermatogenic ability than those with other haplotypes, Yfm1 class A or A* with the least number of copies may be related to the haplotype II-specific structure of the Y chromosome, such as deletion of DAZ or DAZ repeats, reflecting the lower spermatogenic abilities of Japanese haplotype II men. Thus, Yfm1 represents a very useful marker for analysis of genetic structure in different populations and studies on Y chromosome lineage-specific genotype-phenotype correlations.

Alleles↗

Pro-oxidant action of diphenyl diselenide in the yeast Saccharomyces cerevisiae exposed to ROS-generating conditions.

Organoselenium compounds have a potential thiol peroxidase-like activity. Diphenyl diselenide (DPDS) is an electrophilic reagent used in the synthesis of a variety of pharmacologically active organic selenium compounds. Using TRAP assay of chemiluminescense we have shown that diphenyl diselenide clearly possesses a pro-oxidant property. For an investigation on the mechanisms of this property, we used mutant strains of Saccharomyces cerevisiae defective in antioxidant defenses, i.e. in superoxide dismutase, in biosynthesis of glutathione, and the transcription factor yAP-1-lacking yap 1 mutant that cannot activate genes of the oxidative stress response. Exposure of growing cultures to the drug increased cell sensitivity to oxidizing agents. The pro-oxidant effect was independent of the metabolic condition or of the oxidative mutagen tested. N-acetylcysteine, a precursor of glutathione biosynthesis, could neutralize the pro-oxidant effects of diphenyl diselenide by stimulating an increase of endogenous glutathione biosynthesis or by directly binding to the drug. Vitamin E (Trolox), a known antioxidant, was also able to protect S. cerevisiae against the pro-oxidant effect of diphenyl diselenide. In vitro assays showed that diphenyl diselenide interacts non-enzymatically with the thiol group of glutathione.

Antimetabolites, Antineoplastic↗

Transcriptional regulation of the squalene synthase gene (ERG9) in the yeast Saccharomyces cerevisiae.

The ergosterol biosynthetic pathway is a specific branch of the mevalonate pathway. Since the cells requirement for sterols is greater than for isoprenoids, sterol biosynthesis must be regulated independently of isoprenoid biosynthesis. In this study we explored the transcriptional regulation of squalene synthase (ERG9) in Saccharomyces cerevisiae, the first enzyme dedicated to the synthesis of sterols. A mutant search was performed to identify genes that were involved in the regulation of the expression of an ERG9-lacZ promoter fusion. Mutants with phenotypes consistent with known sterol biosynthetic mutations (ERG3, ERG7, ERG24) increased expression of ERG9. In addition, treatment of wild-type cells with the sterol inhibitors zaragozic acid and ketoconazole, which target squalene synthase and the C-14 sterol demethylase respectively, also caused an increase in ERG9 expression. The data also demonstrate that heme mutants increased ERG9 expression while anaerobic conditions decreased expression. Additionally, the heme activator protein transcription factors HAP1 and HAP2/3/4, the yeast activator protein transcription factor yAP-1, and the phospholipid transcription factor complex INO2/4 regulate ERG9 expression. ERG9 expression is decreased in hap1, hap2/3/4, and yap-1 mutants while ino2/4 mutants showed an increase in ERG9 expression. This study demonstrates that ERG9 transcription is regulated by several diverse factors, consistent with the idea that as the first step dedicated to the synthesis of sterols, squalene synthase gene expression and ultimately sterol biosynthesis is highly regulated.

Base Sequence↗

The University of Minnesota Youth and AIDS Projects' Adolescent Early Intervention Program: a model to link HIV-seropositive youth with care.

The survival of human immunodeficiency virus (HIV)-positive adolescents may be abbreviated by delays in health care delivery. Methods of linking youth with services have not been well studied. With support from the Special Projects of National Significance Program, the Youth and Acquired Immunodeficiency Syndrome (AIDS) Projects' (YAP) Adolescent Early Intervention Program offers early intervention health care services to all affected youth in Minnesota, a state with mandatory reporting of HIV/AIDS cases. The conceptual framework is a novel application of traditional public health disease surveillance strategies to link HIV-positive adolescents with health care services. The target population is composed of all 13-22-year-old HIV-positive persons reported to the Minnesota Department of Health (MDH). MDH staff locate and contact HIV-positive youth, conduct structured interviews regarding health status and needs, and facilitate enrollment at YAP. Sixteen male and 20 female participants (mean age 21 years; 56% people of color; 32% gay or bisexual) reported serious health risks, including inconsistent condom use (83%), poverty (78%), high school dropout (56%), unemployment (50%), illegal conduct (50%), medical debt (42%), unstable living situations (33%), running away (33%), substance abuse (33%) and attempted suicide (28%). More than one third reported each of six HIV-related symptoms. Seventy-five percent of participants sought advocacy/case coordination; 56%, clinical trials of experimental therapies; and 50%, vocational training and access to entitlement/eligibility programs. Linking HIV-positive youth to care is a valuable extension of the work of disease intervention specialists in states with similar reporting systems.

Acquired Immunodeficiency Syndrome↗

Y chromosome DNA polymorphisms and their haplotypes in a Japanese population.

Allele frequencies of two Y chromosome-specific short tandem repeats, locus DYS385 and DYS19, in addition to the Y Alu polymorphic (YAP) insert (DYS287) were investigated in blood samples obtained from 270 unrelated Japanese in Miyazaki Prefecture (south Japan). A total of 47 genotypes in DYS385 and 6 in DYS19 were detected, and the frequency of the YAP(+) allele was found to be 35.2% (95270). The allele distributions of each locus revealed significant differences compared with those in other populations. One hundred and twelve different haplotypes were observed in the combined 55 alleles of three loci. The gene diversity values range 0.96 for DYS385 and 0.71 for DYS19, and the combination haplotype diversity value is 0.98.

Journal Article↗

Engineered Saccharomyces cerevisiae strain BioS-OS1/2, for the detection of oxidative stress.

One of the major stress factors during space and high-altitude flight is the oxidative damage caused by the release of reactive oxygen intermediates (ROIs) in human tissues. ROIs are released in response to several stress factors including radiation in space. Since ROIs contribute to several pathological conditions, there has been a great interest in developing a biosensor that can monitor the impact of ROIs on biological systems. Toward this goal, we sought to engineer a yeast stain that can monitor oxidative stress and be easily integrated into a biosensor platform. Saccharomyces cerevisiae respond to hyperoxidative stress by activating the expression of many proteins including the transcription factor, Yap1. Activated Yap1 primarily binds to the Yap-1 response elements in the promoters of genes that combat oxidative stress. Based on these observations, we genetically altered the Yap-1 pathway in the YCR094W BY4742 strain of S. cerevisiae by fusing the YREs in the promoter region of TRX2 gene to a cDNA-insert encoding green fluorescent protein (GFP). Exposure of this engineered yeast strain BioS-OS1 to varying levels of oxidative stress, as generated by different concentrations of H(2)O(2) or diamide, elicits robust expression of GFP that can be monitored by the fluorescence of GFP by as early as 1 h. BioS-OS1 can detect a H(2)O(2) concentration from 300 microM onward. We also show that the signaling strength of the strain can be increased by engineering multiple YREs in the upstream of the cDNA-insert encoding GFP. Thus, the results presented here demonstrate that the engineered BioS-OS yeast strain can detect ROI-generating oxidative stress and validate the use of this prototypic strain for the development of a biosensor to detect and monitor oxidative stress factors during space and high altitude flights.

Biosensing Techniques↗

Y chromosomal polymorphisms reveal founding lineages in the Finns and the Saami.

Y chromosomal polymorphisms were studied in 502 males from 16 Eurasian ethnic groups including the Finns, Saami (Inari Lake area and Skolt Saami), Karelians, Mari, Mokshas, Erzas, Hungarians (Budapest area and Csángós), Khanty, Mansi, Yakuts, Koryaks, Nivkhs, Mongolians, and Latvians. The samples were analysed for polymorphisms in the Y chromosome specific Alu insertion (YAP) and six microsatellites (DYS19, DYS389-I and II, DYS390, DYS392, DYS393). The populations were also screened for the recently described Tat polymorphism. The incidence of YAP+ type was highest in the Csángós and in other Hungarians (37.5% and 17.5%, respectively). In the Karelians and the Latvians it was present at approximately the same level as commonly found in other European populations, whilst absent in our further samples of Eurasian populations, including the Finns and the Saami. Aside from the Hungarians, the C allele of the Tat polymorphism was common in all the Finno-Ugric speaking populations (from 8.2% to 63.2%), with highest incidence in the Ob-Ugrian Khanty. The C allele was also found in the Latvians (29.4%). The haplotypes found associated with the Tat C allele showed consistently lower density than those associated with the T allele, indicating that the T allele is the original form. The computation of the age of the Tat C suggested that the mutation might be a relatively recent event giving a maximum likelihood estimate of 4440 years (95% confidence interval about 3140-6200 years). The distribution patterns of the 222 haplotypes found varied considerably among the populations. In the Finns a majority of the haplotypes could be assigned to two distinct groups, one of which harboured the C allele of the Tat polymorphism, indicating dichotomous primary source of genetic variation among Finnish males. The presence of a bottleneck or founding effect in the male lineages of some of the populations, namely in the Finns and the Saami, would appear to be one likely interpretation for these findings.

Alu Elements↗

Redox control of AP-1-like factors in yeast and beyond.

Cells have evolved complex and efficient strategies for dealing with variable and often-harsh environments. A key aspect of these stress responses is the transcriptional activation of genes encoding defense and repair proteins. In yeast members of the AP-1 family of proteins are required for the transcriptional response to oxidative stress. This sub-family of AP-1 (called yAP-1) proteins are sensors of the redox-state of the cell and are activated directly by oxidative stress conditions. yAP-1 proteins are bZIP-containing factors that share homology to the mammalian AP-1 factor complex and bind to very similar DNA sequence sites. The generation of reactive oxygen species and the resulting potential for oxidative stress is common to all aerobically growing organisms. Furthermore, many of the features of this response appear to be evolutionarily conserved and consequently the study of model organisms, such as yeast, will have widespread utility. The important structural features of these factors, signaling pathways controlling their activity and the nature of the target genes they control will be discussed.

Animals↗

Diversity of the human Y chromosome of South American Amerindians: a comparison with blacks, whites, and Japanese from Brazil.

We defined the Y-chromosome haplotypes on the basis of six polymorphic sites: an Alu-element insertion (YAP), a single-base change (C-->T at DYS199), one trinucleotide repeat (DYS392) and three tetranucleotide repeats (DYS393, DYS390 and DYS19). Among 140 Y chromosomes from Whites, Blacks, Japanese and Amerindians we identified 67 different haplotypes, the majority of them population-specific; only seven haplotypes were shared by three different racial groups, mostly owing to admixture. Overall, three main lineages can be defined on the basis of the YAP/DYS199/DYS392 markers: (a) a predominant /-/C/10/13/22 (or) 23/ lineage, observed among all racial groups; (b) a/+/C/ lineage which predominates among Blacks (comprising mainly the sublineage /+/C/10/13/), although it is eventually found among Japanese and Whites; and (c) a /-/T/ lineage observed only among Amerindians (comprising mainly the sublineage /-/T/13/13/). The decreasing haplotype diversity of the three lineages agrees with the idea that the first is the most ancient, while the last is the more recent. The data also indicate that the YAP insertion occurred in a /-/C/10/13/ chromosome and the C-->T mutation occurred in a /-/C/13/13/ chromosome. Finally, the data suggest that at least two Y-chromosome lineages (/-/C/13/ and /-/T/13/) contributed to the early peopling of the Americas, and supports the hypothesis that /-/T/13/ could be derived from /-/C/13/ and that both haplotypes could be present in the ancestral populations that peopled the continent.

Alleles↗

A WW domain protein TAZ is a critical coactivator for TBX5, a transcription factor implicated in Holt-Oram syndrome.

The T-box transcription factor TBX5 plays essential roles in cardiac and limb development. Various mutations in the TBX5 gene have been identified in patients with Holt-Oram syndrome, which is characterized by congenital defects in the heart and upper extremities. In this study, we identified a WW-domain-containing transcriptional regulator TAZ as a potent TBX5 coactivator. TAZ directly associates with TBX5 and markedly stimulates TBX5-dependent promoters by interacting with the histone acetyltransferases p300 and PCAF. YAP, a TAZ-related protein with conserved functional domains, also stimulates TBX5-dependent transcription, possibly by forming a heterodimer with TAZ. TBX5 lacks a PY motif, which mediates the association of other proteins with TAZ, and interacts with TAZ through multiple domains including its carboxyl-terminal structure. Truncation mutants of TBX5 identified in patients with Holt-Oram syndrome were markedly impaired in their ability to associate with and be stimulated by TAZ. These findings reveal key roles for TAZ and YAP in the control of TBX5-dependent transcription and suggest the involvement of these coactivators in cardiac and limb development.

Abnormalities, Multiple↗

Y chromosomes traveling south: the cohen modal haplotype and the origins of the Lemba--the "Black Jews of Southern Africa".

The Lemba are a traditionally endogamous group speaking a variety of Bantu languages who live in a number of locations in southern Africa. They claim descent from Jews who came to Africa from "Sena." "Sena" is variously identified by them as Sanaa in Yemen, Judea, Egypt, or Ethiopia. A previous study using Y-chromosome markers suggested both a Bantu and a Semitic contribution to the Lemba gene pool, a suggestion that is not inconsistent with Lemba oral tradition. To provide a more detailed picture of the Lemba paternal genetic heritage, we analyzed 399 Y chromosomes for six microsatellites and six biallelic markers in six populations (Lemba, Bantu, Yemeni-Hadramaut, Yemeni-Sena, Sephardic Jews, and Ashkenazic Jews). The high resolution afforded by the markers shows that Lemba Y chromosomes are clearly divided into Semitic and Bantu clades. Interestingly, one of the Lemba clans carries, at a very high frequency, a particular Y-chromosome type termed the "Cohen modal haplotype," which is known to be characteristic of the paternally inherited Jewish priesthood and is thought, more generally, to be a potential signature haplotype of Judaic origin. The Bantu Y-chromosome samples are predominantly (>80%) YAP+ and include a modal haplotype at high frequency. Assuming a rapid expansion of the eastern Bantu, we used variation in microsatellite alleles in YAP+ sY81-G Bantu Y chromosomes to calculate a rough date, 3,000-5,000 years before the present, for the start of their expansion.

Africa, Southern↗

Measuring the imaged-object distance with a stationary high-spatial-resolution scintillation camera.

A method to measure the detector-to-object distance from the images obtained with stationary high-spatial-resolution gamma-ray cameras for in vivo studies has been developed. It exploits the shift of the imaged object in the image plane, obtained at a certain tilt of the parallel-hole collimator. A linear dependence of the image displacement on the distance to the object has been measured using a high-spatial-resolution scintillation camera employing an yttrium-aluminium perovskite (YAP) scintillator. It is shown that the modified YAP camera can be used to obtain three-dimensional information without moving the camera or the object. The method could be applied in scintimammography and radioguided surgery, in lymphoscintigraphy, as well as in the analysis of the biodistribution of radiopharmaceuticals.

Algorithms↗

Worldwide distribution of human Y-chromosome haplotypes.

We surveyed several human populations worldwide with three PCR-based polymorphisms located in the human Y chromosome: the alphoid heteroduplex [alpha(h)] polymorphic system, the DYS19 microsatellite locus, and a polymorphic Alu insertion (YAP). By typing with the former two polymorphisms [alpha(h) and DYS19] we found 46 different haplotypes in 364 males from several populations worldwide. There were significant geographic differences in the distribution of the haplotypes, several of which were seen in only one population and can be used as populational markers in future surveys. The haplotypic diversity in major ethnic groups revealed high levels in Greater Asians, followed by Africans and Caucasians, and a very low diversity was seen in Amerindians. The discrimination probability of such haplotypes for a random sample of Brazilian Caucasians was 0.82, suggesting great potential usefulness in forensic studies. The parsimonious relationship between different alpha(h) types and the addition of the YAP polymorphism data allowed the construction of an informative picture of the origin and evolution of the antiquity of the alpha(h) polymorphism. The DYS19 allele diversity related to each alpha(h) type allowed a crude estimation of the antiquity of many alpha(h) types. These ancient alpha(h) types were present in different populations suggesting a common ancestor that could antedate the first out-of-Africa migrations.

Ethnicity↗

The effect of thermocycling and dentine pre-treatment on the durability of the bond between composite resin and dentine.

The high bond strength between restorative resin and dentine plays an important role in long-term performance of restorations in the oral environment. A variety of treatment techniques have been described to enhance the bond strength of composite resin to dentine. Unfortunately, few studies have reported available bond durability of adhesive resins to dentine. The purpose of this research was to study the shear bond strength of composite resin to dentine pre-treated with phosphoric acid, self-etching agent or Nd:YAP laser irradiation. The durability of bond strength between resin and dentine stored in the artificial saliva thermocycling between 5 and 55 degrees C was also evaluated. The scanning electron microscope was used to assess the treated-dentine surfaces. The mean value of the shear bond strength in the acid-etching group (18.2 +/- 4.9 MPa) was the highest among the three dentine treatments (self-etching system: 12.6 +/-3.0 MPa, Nd:YAP laser: 13.4 +/- 3.3 MPa) prior to thermocycling. After thermocycling, shear strength values of all treated dentines decreased with increasing number of the cycles. When subjected to 3000 thermocycles, the mean bond strengths of these pre-treated samples to composite resin became 9.1 +/- 1.4, 7.8 +/- 1.8, and 8.1 +/- 1.7 MPa for acid-etching, self-etching and laser-irradiation, respectively, with a significant reduction of 38-50%.

Acid Etching, Dental↗

Creating a safer school environment for lesbian and gay students.

Information obtained from clinical experiences of the University of Minnesota Youth and AIDS Project (YAP), a primary AIDS prevention program for gay and bisexual males ages 14-21, is described. More than 300 YAP clients have been interviewed regarding sexual behavior, suicide attempts, drug use, and experiences in disclosing their homosexuality to peers and parents during their high school years. The authors also have drawn from their experiences as support group leaders for gay, lesbian, and bisexual youth in high school and community settings. Constructive and destructive coping strategies employed by gay, lesbian, and bisexual students are described. Roles and responsibilities of school professionals to create a safer school environment also are presented. Key issues include how school professionals support or deny the existence of homosexuality in young people; how adults' biases against homosexuality, as well as institutionalized heterosexism, prevent lesbian and gay students from succeeding in school; how language, behaviors, and environmental cues contribute to school professionals' approachability; how children of lesbian and gay parents suffer when negative attitudes toward homosexuality are not challenged; and what resources and referrals can help lesbian and gay young people.

Acquired Immunodeficiency Syndrome↗

Responses of squirrel monkeys to their experimentally modified mobbing calls.

Previous acoustic analyses suggested emotion-correlated changes in the acoustic structure of squirrel monkey (Saimiri sciureus) vocalizations. Specifically, calls given in aversive contexts were characterized by an upward shift in frequencies, often accompanied by an increase in amplitude. In order to test whether changes in frequencies or amplitude are indeed relevant for conspecific listeners, playback experiments were conducted in which either frequencies or amplitude of mobbing calls were modified. Latency and first orienting response were measured in playback experiments with six adult squirrel monkeys. After broadcasting yaps with increased frequencies or amplitude, squirrel monkeys showed a longer orienting response towards the speaker than after the corresponding control stimuli. Furthermore, after broadcasting yaps with decreased frequencies or amplitude, squirrel monkeys showed a shorter orienting response towards the speaker than after the corresponding manipulated calls with higher frequencies or amplitude. These results suggest that changes in frequencies or amplitude were perceived by squirrel monkeys, indicating that the relationship between call structure and the underlying affective state of the caller agreed with the listener's assessment of the calls. However, a simultaneous increase in frequencies and amplitude did not lead to an enhanced response, compared to each single parameter. Thus, from the receiver's perspective, both call parameters may mutually replace each other.

Animals↗

African origin of modern humans in East Asia: a tale of 12,000 Y chromosomes.

To test the hypotheses of modern human origin in East Asia, we sampled 12,127 male individuals from 163 populations and typed for three Y chromosome biallelic markers (YAP, M89, and M130). All the individuals carried a mutation at one of the three sites. These three mutations (YAP+, M89T, and M130T) coalesce to another mutation (M168T), which originated in Africa about 35,000 to 89,000 years ago. Therefore, the data do not support even a minimal in situ hominid contribution in the origin of anatomically modern humans in East Asia.

Africa↗