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PubMed2001

DNA diversity and population admixture in Anatolia.

The Turkic language was introduced in Anatolia at the start of this millennium, by nomadic Turkmen groups from Central Asia. Whether that cultural transition also had significant population-genetics consequences is not fully understood. Three nuclear microsatellite loci, the hypervariable region I of the mitochondrial genome, six microsatellite loci of the Y chromosome, and one Alu insertion (YAP) were amplified and typed in 118 individuals from four populations of Anatolia. For each locus, the number of chromosomes considered varied between 51-200. Genetic variation was large within samples, and much less so between them. The contribution of Central Asian genes to the current Anatolian gene pool was quantified using three different methods, considering for comparison populations of Mediterranean Europe, and Turkic-speaking populations of Central Asia. The most reliable estimates suggest roughly 30% Central Asian admixture for both mitochondrial and Y-chromosome loci. That (admittedly approximate) figure is compatible both with a substantial immigration accompanying the arrival of the Turkmen armies (which is not historically documented), and with continuous gene flow from Asia into Anatolia, at a rate of 1% for 40 generations. Because a military invasion is expected to more deeply affect the male gene pool, similar estimates of admixture for female- and male-transmitted traits are easier to reconcile with continuous migratory contacts between Anatolia and its Asian neighbors, perhaps facilitated by the disappearance of a linguistic barrier between them.

Adult↗
PubMed2004

Y-chromosomal microsatellite mutation rates: differences in mutation rate between and within loci.

Precise estimates of mutation rates at Y-chromosomal microsatellite STR (short tandem repeat) loci make an important basis for paternity diagnostics and dating of Y chromosome lineage origins. There are indications of considerable locus mutation rate variability between (inter-) and within (intra-) loci. We have studied nine Y-STR loci-DYS19, DYS389I/II, DYS390, DYS391, DYS392, DYS393, DYS385, and DYS388-in 1,766 father-son pairs of confirmed paternity (a total of 15,894 meioses). Five biallelic markers were also analyzed in the fathers-Tat, YAP, 12f2, SRY1532, and 92R7-defining haplogroups 1, 2, 3, 4, 9, and 16, respectively. A total of 36 fragment length mutations were observed: 24 gains (22 single-step, two double-step) and 12 single-step losses. Thus, there was a significant surplus of gains (p=0.045). Overall, the mutation rate was positively correlated to STR repeat length and there was a significant relative excess of losses in long alleles and gains in short alleles (p=0.043). In contrast to the situation in autosomal STR loci and in MSY-1, no noteworthy correlation between mutation rate and the father's age at the child's birth was observed. We observed significant interlocus differences in Y-STR mutation rates (p<0.01). The number of observed mutations ranged from zero in DYS392 to eight in DYS391 and DYS390. We have also demonstrated obvious differences in mutation rates between the haplogroups studied (p=0.024), a phenomenon that is a reflection of the dependence of mutation rate on allele size. Our study has thus demonstrated the necessity of not only locus-specific, but even allele-specific, mutation rate estimates for forensic and population genetic purposes, and provides a considerable basis for such estimates.

Adolescent↗
PubMed2006

Transcriptional co-repressors of Runx2.

Runx2 is an essential transcription factor for skeletal mineralization because it stimulates osteoblast differentiation of mesenchymal stem cells, promotes chondrocyte hypertrophy, and contributes to endothelial cell migration and vascular invasion of developing bones. Runx2 is also expressed during mouse embryo development in nascent mammary gland epithelium. Recent evidence implicates deregulation of Runx2 as a contributing factor in breast cancer-induced osteolysis and invasion, as well as in ectopic vascular calcification. Like other Runt domain proteins, Runx2 is a context-dependent transcriptional activator and repressor of genes that regulate cellular proliferation and differentiation. Proteins that temporally and spatially associate with Runx2 dictate these opposing transcriptional activities. Recent studies have identified several co-repressor proteins that bind to Runx2 to regulate gene expression. These co-factors include histone deacetylases (HDACs), transducin-like enhancer of split (TLE) proteins, mSin3a, and yes-associated protein (YAP). These proteins do not bind DNA themselves and appear to act by preventing Runx2 from binding DNA, altering chromatin structure, and/or by possibly blocking co-activator complexes. The nuclear localization of several of these factors is regulated by extracellular signaling events. Understanding the mechanisms whereby co-repressor proteins affect Runx2 activity during normal cellular development and tumor progression will identify new therapeutic targets for skeletal disorders such as osteoporosis and for bone metastatic cancers.

Animals↗
PubMed2006

Alterations in intranuclear localization of Runx2 affect biological activity.

The transcription factor Runx2 controls osteoblast proliferation and differentiation. Runx2 organizes and assembles gene-regulatory complexes in nuclear microenvironments where target genes are activated or suppressed in a context-dependent manner. Intranuclear localization of Runx2 is mediated by the nuclear matrix-targeting signal (NMTS), an autonomous motif with a loop (L1)-turn-loop (L2) structure that forms predicted protein-protein interaction surfaces. Here we examined the functional consequences of introducing mutations in the L1 and L2 loops of the NMTS. These mutant proteins enter the nucleus, interact with the hetero-dimeric partner Cbfbeta, and bind to DNA in vitro and in vivo. In addition, these mutants retain interaction with the carboxy-terminus interacting co-regulatory proteins that include TLE, YAP, and Smads. However, two critical mutations in the L2 domain of the NMTS decrease association of Runx2 with the nuclear matrix. These subnuclear targeting defective (STD) mutants of Runx2 compromise target gene activation or repression. The biological significance of these findings is reflected by decreased osteogenic differentiation of mesenchymal progenitors, concomitant with major changes in gene expression profiles, upon expression of the STD Runx2 mutant. Our results demonstrate that fidelity of temporal and spatial localization of Runx2 within the nucleus is functionally linked with biological activity.

Amino Acids↗
PubMed1985

The interrelationship of tropical disease and mental disorder: conceptual framework and literature review (Part I--Malaria).

Substantial interactions between tropical diseases and psychiatric illness have long been recognized, but the impact of biological factors in the field of cross-cultural psychiatry has been less well studied than psychosocial factors. In reviewing the literature at the intersection of tropical medicine and psychiatry in order to summarize the existing data base in this field, a generalized interactive model informed by the theoretical contributions of George Engel, the WHO Scientific Working Group on Social and Economic Research, Arthur Kleinman, P. M. Yap, Edward Sapir and others has been developed to serve as a conceptual framework for this analysis of the literature and to guide further research. The clinical literature of tropical medicine and psychiatry which recognizes the significance of concurrent tropical disease and mental disorders is reviewed along with the more specific literature on malaria and concomitant psychiatric illness. Many authors have focused on the role of organic mental disorders, especially in connection with cerebral malaria, but several have also addressed psychosocial parameters through which the interrelationship between malaria and a full range of mental disorders is also mediated. The effects of malaria may serve as biological, psychological or social stressors operating in a cultural context which precipitate or shape features of psychiatric symptomatology. Psychiatric illness may likewise precipitate an episode of malaria with typical symptoms in a patient with a previously subclinical infection. Implications of the literature and this generalized interactive model are considered as they apply to clinical practice, public health and the application of social science theory in medicine.

Cross-Cultural Comparison↗
PubMed1986

Adolescent pregnancy: the perspective of the sisterhood of black single mothers.

The Sisterhood of Black Single Mothers Inc. (The Sisterhood) is an organization which exemplifies the considerable potential of community members united for a common good. The Sisterhood began eleven years ago under the leadership of Ms. Daphne Busby. The objective of the Sisterhood is "salvation of a generation subject to insensitivity and misunderstanding--through helping families, especially those headed by women and adolescent women--to establish a new and positive mind set." The Sisterhood regards individuals and social phenomenon as parts of a complex and dynamic whole and uses a positive approach to assessment of situations. Therefore, adolescents who come to the Sisterhood already parents, as well as those who may become parents in their formative years, are provided programming appropriate to their overall needs. They are given opportunities for help in such areas as: securing medical care, public assistance, counseling, housing and financial assistance. Outreach to other significant persons in the life of these adolescents includes intervention with the service providers with whom they come in contact (doctors, teachers, social workers etc.). In addition to addressing the practical needs of adolescents who come to the Sisterhood, positive examples of healthy ways of relating to others and presentation of a system of values consonant with self and family development are provided. Examples are: the Youth Awareness Project (YAP) which deals with concerns of young people as a specific group. The program's focus is bringing young people together who are growing in positive ways and encouraging continuation of that growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Characterization of calsequestrin of avian skeletal muscle.

A calsequentrin (CS)-like glycoprotein is present in the sarcoplasmic reticulum (SR) of chicken pectoralis muscle, which displays unusual properties: it binds relatively low amounts of Ca2+, compared to CS in mammalian skeletal muscle (Yap & MacLennan, 1976), it does not exhibit a marked pH-dependent shift in mobility in sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), and its metachromatic staining properties with Stains All are likewise peculiar (Damiani et al., 1986). We have now definitively localized the same protein to the junctional terminal cisternae (TC) fraction of the SR of chicken pectoralis muscle and have further characterized it, following purification by crystallization with Ca2+ and by Ca2(+)-dependent elution from phenyl-Sepharose columns. The purified protein (apparent Mr: 51 kDa), isoelectrofocuses at pH 4.5, and is readily identified on blots by a 45Ca overlay technique, similar to CS of rabbit skeletal muscle, but it binds half as much Ca2+ (about 20 moles of Ca2+ per mole of protein), as estimated by equilibrium dialysis. However, the chicken protein shares extensive similarities with mammalian CSs, concerning Ca2(+)-induced changes in maximum intrinsic fluorescence and the Ca2(+)-modulated interaction with phenyl-Sepharose, as well as in being protected by Ca2+ from proteolysis by either trypsin or chymotrypsin. We discuss how the presence of a Ca2(+)-regulated hydrophobic site in the CS molecule appears to be the most invariant property of the CS-family of Ca2(+)-binding proteins.

Animals↗
PubMed2005

Contrasting patterns of Y-chromosome variation in South Siberian populations from Baikal and Altai-Sayan regions.

In order to investigate the genetic history of autochthonous South Siberian populations and to estimate the contribution of distinct patrilineages to their gene pools, we have analyzed 17 Y-chromosomal binary markers (YAP, RPS4Y(711), SRY-8299, M89, M201, M52, M170, 12f2, M9, M20, 92R7, SRY-1532, DYS199, M173, M17, Tat, and LLY22 g) in a total sample of 1,358 males from 14 ethnic groups of Siberia (Altaians-Kizhi, Teleuts, Shors, Tuvinians, Todjins, Tofalars, Sojots, Khakassians, Buryats, Evenks), Central/Eastern Asia (Mongolians and Koreans) and Eastern Europe (Kalmyks and Russians). Based on both, the distribution pattern of Y-chromosomal haplogroups and results on AMOVA analysis we observed the statistically significant genetic differentiation between the populations of Baikal and Altai-Sayan regions. We suggest that these regional differences can be best explained by different contribution of Central/Eastern Asian and Eastern European paternal lineages into gene pools of modern South Siberians. The population of the Baikal region demonstrates the prevalence of Central/Eastern Asian lineages, whereas in the populations of Altai and Sayan regions the highest paternal contribution resulted from Eastern European descent is revealed. Yet, our data on Y-chromosome STRs variation demonstrate the clear differences between the South Siberian and Eastern European R1a1-lineages with the evolutionary ages compatible with divergence time between these two regional groups.

Chromosomes, Human, Y↗
PubMed2004

Genetic origins of the Ainu inferred from combined DNA analyses of maternal and paternal lineages.

The Ainu, a minority ethnic group from the northernmost island of Japan, was investigated for DNA polymorphisms both from maternal (mitochondrial DNA) and paternal (Y chromosome) lineages extensively. Other Asian populations inhabiting North, East, and Southeast Asia were also examined for detailed phylogeographic analyses at the mtDNA sequence type as well as Y-haplogroup levels. The maternal and paternal gene pools of the Ainu contained 25 mtDNA sequence types and three Y-haplogroups, respectively. Eleven of the 25 mtDNA sequence types were unique to the Ainu and accounted for over 50% of the population, whereas 14 were widely distributed among other Asian populations. Of the 14 shared types, the most frequently shared type was found in common among the Ainu, Nivkhi in northern Sakhalin, and Koryaks in the Kamchatka Peninsula. Moreover, analysis of genetic distances calculated from the mtDNA data revealed that the Ainu seemed to be related to both the Nivkhi and other Japanese populations (such as mainland Japanese and Okinawans) at the population level. On the paternal side, the vast majority (87.5%) of the Ainu exhibited the Asian-specific YAP+ lineages (Y-haplogroups D-M55* and D-M125), which were distributed only in the Japanese Archipelago in this analysis. On the other hand, the Ainu exhibited no other Y-haplogroups (C-M8, O-M175*, and O-M122*) common in mainland Japanese and Okinawans. It is noteworthy that the rest of the Ainu gene pool was occupied by the paternal lineage (Y-haplogroup C-M217*) from North Asia including Sakhalin. Thus, the present findings suggest that the Ainu retain a certain degree of their own genetic uniqueness, while having higher genetic affinities with other regional populations in Japan and the Nivkhi among Asian populations.

Asian People↗
PubMed2006

Study of AZFc partial deletion gr/gr in fertile and infertile Japanese males.

A recurrent partial azoospermia factor C (AZFc) deletion, called gr/gr, has been reported to be a male infertility risk factor. A specific type of Y chromosome observed in approximately 30% of Japanese males (haplogroup D derived at YAP+) is believed to have a fixed gr/gr deletion. A recent study claimed that spermatogenic failure is more likely in males with D Y chromosomes, because of the gr/gr deletion, the presence of which is not well characterized among D haplogroup chromosomes. We therefore decided to perform a systematic study of the frequency of the gr/gr deletion in the Japanese. We studied fertile and infertile males to investigate the possibility of different gr/gr frequencies. The deletions were detected by use of single tagged-sequences (STSs) and the D haplogroup sub-lineages typing were done by use of the biallelic markers M174, M64, M116.1, 12f2.2, M15, M151, and M125. Analysis of gr/gr deleted Y chromosomes showed that all are classified as haplogroup D2, suggesting a lineage association. The subtype D2b1 was most frequent among the Japanese, in control and infertile samples. The haplogroups D2b2, D*, and D1 were not found in any population group. Remarkably, we observed no statistical difference between haplogroup D sub-lineages of the infertile and control groups, although the statistical power of this study is low. This study suggests lack of significant evidence of increased infertility risk in haplogroup D Japanese males. We were also able to establish the ancestral chromosome that suffered a gr/gr deletion, and propose a new Y chromosome phylogeny for haplogroup D and its derivatives. In summary, we were able to define the frequency of gr/gr deletion in Japanese males and show that the gr/gr deletion was probably present in the ancestral Y chromosome that entered Japan at least 12,000 years ago.

Asian People↗
PubMed1999

Genetic variations on the Y chromosome in the Japanese population and implications for modern human Y chromosome lineage.

A polymorphism in the coding sequence of the SRY gene was found by single-strand conformation polymorphism (SSCP) and direct sequencing analysis. The new allele of the SRY gene, which is raised by a C-to-T transition in the 155th codon, was found in 24% of Honshu, 35% of Okinawan, and 51% of Korean males respectively, whereas it was not observed among 16 Caucasian and 18 Negroid males. A haplotype analysis of the Y chromosome was carried out in Japanese, Korean, Caucasian and Negroid populations, using a combination of the polymorphisms in SRY, DXYS5Y, DYS287, and DXYS241Y loci. The results indicated that the Y chromosomes can be classified into seven heplotypes (Ia, Ib, Ic, IIa, IIb, III, IV). However, of these seven, only four (Ia, IIa, III, IV) were observed in the Japanese population. Furthermore, the presumed haplotype C, Y1, YAP, (CA)14, from which haplotype III was probably derived, was not found in any populations in this study. The regional distribution of each haplotype revealed that type III is more frequently observed in Okinawa (16%) and in Korea (21%) than in Honshu (4.4%). The haplotype analysis of the Y chromosome may contribute to the exploration of the origin of Japanese and the relationship between east Asian populations.

DNA-Binding Proteins↗
PubMed2002

Microdeletions of a Y-specific marker, Yfm1, and implications for a role in spermatogenesis.

We have detected deletions of a Y-specific microsatellite marker, Yfm1, located on the Y chromosome (Yq) within interval 6 and near the DAZ (deleted in azoospermia) genes, in 9/89 oligospermic and 17/68 azoospermic Japanese men. No Yfm1 deletions were detected in the 150 normal fertile males examined as controls. Yfm1 deletions in the oligo- and azoospermic males were associated with other deletions that removed entire DAZ genes in those infertile men. These deletions indicated that all Yfm1 loci are located within azoospermia factor c (AZFc) in interval 6 on the long arm of the Y chromosome. Mapping Yfm1 on the Y chromosome using the draft sequence of the human genome revealed that at least three Yfm1 loci are located within about 25-30 kbp of the DAZ genes. Moreover, the Yfm1 marker showed the least number of copies in Japanese males derived from a Y chromosomal lineage called haplotype II, defined by having the Y Alu polymorphism (YAP) insertion. Males from this haplotype II lineage are known from our previous studies to have lower spermatogenic abilities, with higher rates of oligo- and azoospermia than other haplotypes. The least number of Yfm1 loci, whose copy number may correspond to that of the DAZ genes, may be a risk factor predisposing an individual to azoospermia or oligospermia.

Alu Elements↗
PubMed2026

Molecular insights and therapeutic innovations in low-risk human papillomavirus-associated cutaneous wart.

Human papillomavirus (HPV) is a DNA virus that belongs to the Papillomaviridae family. Among the various types, high-risk strains are associated to malignancy, whereas low-risk types cause benign skin warts due to persistent infection. Unlike high-risk HPVs, low-risk HPV genomes remain in an episomal state while expressing E6/E7 proteins. These proteins exhibit a reduced ability to degrade pRb and p53, which finally leads to controlled epithelial hyperplasia instead of developing malignancy. Infection with low-risk HPV activates distinct host signaling pathways, ultimately promoting the proliferation of keratinocytes and formation of warts. Simultaneously, it triggers host innate and adaptive immune responses that often clear the lesion. This review focuses on low-risk types that cause skin warts by analyzing the molecular pathways, particularly the integrin-FAK-PI3K/AKT, Hippo-YAP/TAZ pathway along with MAPK-ERK pathways that promotes cutaneous benign wart formation. This article further studies clinical management strategies for HPV associated warts, including primary destructive treatment (cryotherapy, keratolytics, excision), immunotherapies (imiquimod, interferon injections or intralesional antigen), and novel adjunctive therapies with clinical evidence including photodynamic therapy, intralesional chemotherapeutics, and emerging HPV vaccination strategies. Among these, for benign skin warts, intralesional immunotherapy, particularly Candida antigen, and intralesional HPV vaccination have shown encouraging responses clinically. But extensive controlled clinical studies are necessary to establish their efficacy and clinical value as a standard medicine. This review therefore, generates a comprehensive overview of papilloma virus mediated skin warts and their management for both clinicians and researchers.

Humans↗
PubMed1989

Both separation and eccentricity can limit precise position judgements: a reply to Morgan and Watt.

Weber's law is ubiquitous in position judgements. In a variety of position acuity tasks, the position threshold is proportional to the separation of the reference features. Recently, we (Klein & Levi, 1987; Levi, Klein & Yap, 1988) suggested that two sensory processes may serve to limit position acuity, and thus contribute to Weber's law for position. One is the target separation, and the other is the target eccentricity. In order to test this idea, we pitted separation against eccentricity by measuring spatial interval discrimination thresholds on an iso-eccentric arc (Levi et al., 1988). Over a 5-fold range of separations, we found that thresholds were independent of separation, and concluded that at large separations, eccentricity can limit precise position judgements. In the preceding article, Morgan and Watt (1989) have questioned this conclusion, and have shown that the effects of eccentricity are small in an arc length discrimination task. In the present article, we: (i) address the objections raised by Morgan and Watt; (ii) show that our data and 2-mechanism model are consistent with many previous studies; and (iii) show that Morgan and Watt's task is inherently difficult, so that rather than tapping the sensory limits imposed by the target eccentricity, performance on the arc length task is constrained by the cognitive demands of the task, or by the difficulty of reconstruction. In contrast, the measurement of chord length (spatial interval discrimination on an iso-eccentric arc) can be simply done by calculating the distance between the endpoints. Thus, at large separations, thresholds for the chord length judgements are much lower than those of Morgan and Watt, and are proportional to the eccentricity of the targets.

Humans↗
PubMed2006

Synthesis, labeling, and biological evaluation of halogenated 2-quinolinecarboxamides as potential radioligands for the visualization of peripheral benzodiazepine receptors.

The previous exploration of the structure-affinity relationships concerning 4-phenyl-2-quinolinecarboxamide peripheral benzodiazepine receptor (PBR) ligands 6 showed as an interesting result the importance of the presence of a chlorine atom in the methylene carbon at position 3 of the quinoline nucleus. The subnanomolar PBR affinity shown by N-benzyl-3-chloromethyl-N-methyl-4-phenyl-2-quinolinecarboxamide (6b) suggested its chlorine atom to be replaced with other halogens in order to optimize the interaction of the quinolinecarboxamide derivatives with PBR and to develop suitable candidates for positron emission tomography (PET) or single photon emission computed tomography (SPECT) studies. The binding studies led to the discovery of fluoromethyl derivative 6a, which showed an IC50 value of 0.11 nM and is, therefore, one of the most potent PBR ligands so far described. Fluoromethyl derivative 6a has been labeled with 11C (t1/2=20.4 min, beta+=99.8%) starting from the corresponding des-methyl precursor (14) using [11C]CH3I in the presence of tetrabutylammonium hydroxide in DMF with a 35-40% radiochemical yield (corrected for decay) and 1.5 Ci/micromol of specific radioactivity. Ex vivo rat biodistribution and inhibition (following intravenous pre-administration of PK11195) studies showed that [11C]6a rapidly and specifically accumulated in PBR-rich tissues such as heart, lung, kidney, spleen, and adrenal, and at a lower level in other peripheral organs and in the brain. The images obtained in mouse with small animal YAP-(S)PET essentially confirmed the result of the ex vivo biodistribution experiments. The biological data suggest that [11C]6a is a promising radioligand for peripheral benzodiazepine receptor PET imaging in vivo.

Amides↗
PubMed2005

From genome to drug lead: identification of a small-molecule inhibitor of the SARS virus.

Virtual screening, a fast, computational approach to identify drug leads [Perola, E.; Xu, K.; Kollmeyer, T. M.; Kaufmann, S. H.; Prendergast, F. G. J. Med. Chem.2000, 43, 401; Miller, M. A. Nat. Rev. Drug Disc.2002, 1 220], is limited by a known challenge in crystallographically determining flexible regions of proteins. This approach has not been able to identify active inhibitors of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) using solely the crystal structures of a SARS-CoV cysteine proteinase with a flexible loop in the active site [Yang, H. T.; Yang, M. J.; Ding, Y.; Liu, Y. W.; Lou, Z. Y. Proc. Natl. Acad. Sci. U.S.A.2003, 100, 13190; Jenwitheesuk, E.; Samudrala, R. Bioorg. Med. Chem. Lett.2003, 13, 3989; Rajnarayanan, R. V.; Dakshanamurthy, S.; Pattabiraman, N. Biochem. Biophys. Res. Commun.2004, 321, 370; Du, Q.; Wang, S.; Wei, D.; Sirois, S.; Chou, K. Anal. Biochem.2005, 337, 262; Du, Q.; Wang, S.; Zhu, Y.; Wei, D.; Guo, H. Peptides2004, 25, 1857; Lee, V.; Wittayanarakul, K.; Remsungenen, T.; Parasuk, V.; Sompornpisut, P. Science (Asia)2003, 29, 181; Toney, J.; Navas-Martin, S.; Weiss, S.; Koeller, A. J. Med. Chem.2004, 47, 1079; Zhang, X. W.; Yap, Y. L. Bioorg. Med. Chem.2004, 12, 2517]. This article demonstrates a genome-to-drug-lead approach that uses terascale computing to model flexible regions of proteins, thus permitting the utilization of genetic information to identify drug leads expeditiously. A small-molecule inhibitor of SARS-CoV, exhibiting an effective concentration (EC50) of 23 microM in cell-based assays, was identified through virtual screening against a computer-predicted model of the cysteine proteinase. Screening against two crystal structures of the same proteinase failed to identify the 23-microM inhibitor. This study suggests that terascale computing can complement crystallography, broaden the scope of virtual screening, and accelerate the development of therapeutics to treat emerging infectious diseases such as SARS and Bird Flu.

Aminobenzoates↗
PubMed2006

Automated single-trial measurement of amplitude and latency of laser-evoked potentials (LEPs) using multiple linear regression.

OBJECTIVE: Laser stimulation of Adelta-fibre nociceptors in the skin evokes nociceptive-specific brain responses (laser-evoked potentials, LEPs). The largest vertex complex (N2-P2) is widely used to assess nociceptive pathways in physiological and clinical studies. The aim of this study was to develop an automated method to measure amplitudes and latencies of the N2 and P2 peaks on a single-trial basis. METHODS: LEPs were recorded after Nd:YAP laser stimulation of the left hand dorsum in 7 normal volunteers. For each subject, a basis set of 4 regressors (the N2 and P2 waveforms and their respective temporal derivatives) was derived from the time-averaged data and regressed against every single-trial LEP response. This provided a separate quantitative estimate of amplitude and latency for the N2 and P2 components of each trial. RESULTS: All estimates of LEP parameters correlated significantly with the corresponding measurements performed by a human expert (N2 amplitude: R2=0.70; P2 amplitude: R2=0.70; N2 latency: R2=0.81; P2 latency: R2=0.59. All P<0.0001). Furthermore, regression analysis was able to extract an LEP response from a subset of the trials that had been classified by the human expert as without response. CONCLUSIONS: This method provides a simple, fast and unbiased measurement of different components of single-trial LEP responses. SIGNIFICANCE: This method is particularly desirable in several experimental conditions (e.g. drug studies, correlations with experimental variables, simultaneous EEG/fMRI and low signal-to-noise ratio data) and in clinical practice. The described multiple linear regression approach can be easily implemented for measuring evoked potentials in other sensory modalities.

Adult↗
PubMed2004

Yap8p activation in Saccharomyces cerevisiae under arsenic conditions.

Yap8p, a member of the Saccharomyces cerevisiae Yap family, is activated in response to arsenic. Both the mechanisms by which this activation takes place and its regulation have not yet been identified. In this report, we show that Yap8p is not activated at the transcriptional level but, rather, its nuclear transport is actively regulated and dependent on the exportin chromosome region maintenance protein. In addition, it is shown that Cys(132), Cys(137)and Cys(274) are essential for Yap8p localization and transactivation function both of which are required for its biological activity.

Active Transport, Cell Nucleus↗