Miracle-dz/UniFAR-FTUs huggingface dataset:
CYP3A5 phenotype-genotype correlations in a British population.

AIMS To develop a polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP)-based assay to genotype for hepatic CYP3A5 expression and to use this assay to study a British population. METHODS CYP3A5-specific primers were designed with one including a base-pair mismatch to create a RsaI site in samples positive for G6986 (CYP3A5*3 allele) [correction]. Following PCR and RsaI digestion, different band patterns on electrophoresis were predicted for individuals positive for CYP3A5 (CYP3A5*1 allele) compared with those who do not express the gene (CYP3A5*3 homozygotes). The assay was validated by DNA sequencing. DNA samples from a human liver bank consisting of 22 livers whose CYP3A5 expression had been determined by immunoblotting and a group of random individuals (n = 100) from the North-east of England were genotyped by the new assay. RESULTS In the liver bank, five out of 22 samples expressed CYP3A5 at significant levels (>20 pmol mg-1 protein) and were found to have the genotype CYP3A5*1/CYP3A5*3 by the PCR-RFLP assay. All other liver DNA samples were CYP3A5*3 homozygotes. In the group of 100 random individuals, 13 had the genotype CYP3A5*1/CYP3A5*3 and all others were CYP3A5*3 homozygotes, predicting that 13% (95% confidence interval (CI) 6%, 20%) would show significant hepatic CYP3A5 expression. The frequency for the CYP3A5*1 allele was 0.065 (95% CI 0.032, 0.097). CONCLUSIONS We have developed a simple assay for the detection of the CYP3A5*1/CYP3A5*3 alleles and shown that in a British population their frequency is similar to that reported previously. We have also shown a good correlation between hepatic CYP3A5 expression and genotype for a British Caucasian liver bank.
The structure of the genetic and environmental risk factors for six major psychiatric disorders in women. Phobia, generalized anxiety disorder, panic disorder, bulimia, major depression, and alcoholism.

BACKGROUND Although prior family and twin studies have examined the relationship between the genetic and environmental risk factors for pairs of psychiatric disorders, the interrelationship between these classes of risk factors for a broad range of psychiatric disorders remains largely unknown. METHODS An epidemiologic sample of 1030 female-female twin pairs with known zygosity, ascertained from the Virginia Twin Registry, were evaluated by a personal interview conducted by mental health professionals, assessing lifetime history of phobia, generalized anxiety disorder, panic disorder, bulimia nervosa, major depression, and alcoholism. RESULTS A multivariate twin analysis suggested the following. First, genetic, familial-environmental, and individual-specific environmental risk factors each cause a unique pattern of comorbidity among the six disorders. Second, genetic influences on these disorders are best explained by two factors, the first of which loads heavily on phobia, panic disorder, and bulimia nervosa and the second, on major depression and generalized anxiety disorder. Third, unlike other disorders, genetic influences on alcoholism are largely disorder specific. Fourth, familial-environmental influences on these disorders are best explained by a single factor that substantially influenced liability to bulimia nervosa only. Fifth, individual-specific environmental influences on the risk for these psychiatric disorders are best explained by a single factor, with highest loadings on generalized anxiety disorder and major depression and with large-disorder-specific loadings, especially on phobias, panic disorder, and alcoholism. CONCLUSIONS These results support the following hypotheses: First, each major risk factor domain (genes, family environment, and individual-specific environment) influences comorbidity between these disorders in a distinct manner. Second, genetic influences on these six disorders are neither highly specific nor highly nonspecific. Neither a model that contains a discrete set of genetic factors for each disorder nor a model in which all six disorders results from a single set of genes is well supported. Third, the anxiety disorders are not, from a genetic perspective, etiologically homogeneous. Fourth, most of the genetic factors that influence vulnerability to alcoholism in women do not alter the risk for development of other common psychiatric disorders. These results should be interpreted in the context of both the strengths and limitations of multivariate twin analysis.
Temperature-sensitive mutants in rfaI and rfaJ, genes for galactosyltransferase I and glucosyltransferase II, for synthesis of lipopolysaccharide in Salmonella typhimurium.

Certain rough mutants of Salmonella typhimurium LT2 were shown to be temperature sensitive for the production of lipopolysaccharide (LPS). When grown at the restrictive temperature (42 or 45 degrees C), the cells contained LPS deficient in O (somatic) side chains, based on phage-sensitivity data and gel electrophoresis of the LPS. Cells grown at the permissive temperature, 30 degrees C, made LPS resembling that of smooth cells. The mobility of the LPS in gels, the phage sensitivity patterns, and gas chromatographic analysis indicate that LPS of 45 degrees C-grown cells of SA126 (rfaJ3012) is of chemotype Rb2, with one glucose and two galactose units (and thus inferred to be due to a mutation in rfaJ), and LPS of 45 degrees C-grown cells of SA134 (rfa13020) is of chemotype Rb3, with one glucose and one galactose unit (inferred to be rfaI). These inferences were confirmed, for pKZ26 (pBR322-rfaGBIJ) and pKZ27 (pBR322-rfaGBI) both complement rfaI3020, but only pKZ26 complemented rfaJ3012. In addition, pKZ26 carrying a Tn5 insertion resulting in loss of complementation of a known rfaJ mutation, but not of rfaG, B, or I, also resulted in loss of rfaJ3012 complementation. Based on gel analysis, there is a small amount of the LPS containing smooth side chains in cells of SA126 grown at 45 degrees C; following a switch to 30 degrees C, the amount of LPS with O side chains gradually increased, and the amount of core LPS was reduced, though even after 3 h the LPS does not fully resemble that of smooth strains. (ABSTRACT TRUNCATED AT 250 WORDS)
Effects of Fluoride and Aluminum from Ionomeric Materials on S. mutans Biofilm

Ionomeric materials release different proportions of fluoride and aluminum. Their simultaneous effect on the acidogenicity and composition of S. mutans biofilm is unknown. Six cylindrical specimens of each material (Ketac-fil, Vitremer, Fuji-Ortho LC, F-2000, and Z-100) were incubated with S. mutans GS-5 in culture media containing 5% sucrose (w/v). The media were changed daily for seven days, during which the pH and concentrations of fluoride and aluminum were determined. Furthermore, the concentrations of these ions and insoluble polysaccharide were determined in the biofilm formed at the end of the experimental period. The results showed that all the materials tested released fluoride. However, Vitremer released the highest amount of aluminum and was the most effective in reducing the acidogenicity of S. mutans biofilms. It also significantly affected both biofilm formation and composition. Thus, this study suggests that aluminum released by ionomeric materials may enhance the biological effects of fluoride.
Sphingosine 1-Phosphate-induced Cell Proliferation, Survival, and Related Signaling Events Mediated by G Protein-coupled Receptors Edg3 and Edg5*

Sphingosine 1-phosphate (S1P) regulates cell proliferation, apoptosis, motility, and neurite retraction. Contradictory reports propose that S1P acts as either an intracellular second messenger or an extracellular ligand for cell-surface receptors. Hence, the precise signaling mechanisms mediating the diverse cellular effects of S1P remain to be determined. Here, we investigate whether S1P stimulation of cell proliferation, survival, and related signaling events can be mediated by the recently cloned Edg family members of G protein-coupled receptors. We observed that S1P treatment significantly increased proliferation of HTC4 hepatoma cells stably transfected with human S1P receptor Edg3 or Edg5, which was attributable to stimulation of cell growth and inhibition of apoptosis caused by serum starvation. Edg3 and Edg5 transduced S1P-evoked signaling events relevant to cell proliferation and survival, including activation of the ERK/MAP kinases, and immediate-early induction of c-Jun and c-Fos. Trancriptional activation of reporter genes for the c-fospromoter and the serum response element by Edg3 and Edg5 transfected in Jurkat cells was inhibited by pertussis toxin and C3 exoenzyme, implicating Gi/o- and Rho-dependent pathways. Our data also indicated that Edg3 and Edg5 mediated the serum response element activation through transcriptional factors Elk-1 and serum response factor. Thus, specific G protein-coupled receptors Edg3 and Edg5 account for, at least in part, S1P-induced cell proliferation, survival, and related signaling events.
Diagnóstico de Peligros e Identificación de Riesgos de Desastres en México. Atlas Nacional de Riesgos de la República Mexicana

El presente "atlas de riesgos" tiene como proposito general difundir conocimientos sobre los peligros e identificacion de los riesgos de desastres que se presentan en Mexico derivados de los fenomenos de origen geologico, hidrometeorologico, quimico, sanitario y socio-organizativo. Contenido: 1) Introduccion: riesgo de desastres en Mexico; la prevencion de desastres; diagnostico de riesgo; conceptos basico sobre prevencion de desastres; estadisticas de danos. 2) Riesgos geologicos: sismos; tsunamis; volcanes; movimientos de la superficie del terreno natural. 3) Riesgos hidrometeorologicos: precipitacion pluvial; tormentas de granizo y nieve; heladas; ciclones tropicales; escurrimiento; inundaciones; sequia; Erosion; viento; marea de tormenta. 4) Riesgos quimicos: definicion de los riesgos y accidentes de origen quimico y estadisticas de accidentes mundiales; ubicacion y caracteristicas de las fuentes de peligro (zonas industriales, industria petroquimica, tuberia de transporte de gas; estaciones de servicio; fuentes de materiales radiactivos); accidentes relacionados con sustancias quimicas; residuos peligrosos; incendios forestales. 5) Otros riesgos: de origen sanitario y socio-organizativos. 6) Microzonificacion del riesgo: aspectos generales; tecnologias; mapas municipales de riesgo y de escenarios. Cereditos, autorias y bibliografia
Molecular Genetic Dissection of TAF25, an Essential Yeast Gene Encoding a Subunit Shared by TFIID and SAGA Multiprotein Transcription Factors

ABSTRACT We have performed a systematic structure-function analysis of Saccharomyces cerevisiae TAF25, an evolutionarily conserved, single-copy essential gene which encodes the 206-amino-acid TAF25p protein. TAF25p is an integral subunit of both the 15-subunit general transcription factor TFIID and the multisubunit, chromatin-acetylating transcriptional coactivator SAGA. We used hydroxylamine mutagenesis, targeted deletion, alanine-scanning mutagenesis, high-copy suppression methods, and two-hybrid screening to dissect TAF25. Temperature-sensitive mutant strains generated were used for coimmunoprecipitation and transcription analyses to define the in vivo functions of TAF25p. The results of these analyses show that TAF25p is comprised of multiple mutable elements which contribute importantly to RNA polymerase II-mediated mRNA gene transcription.
Stem cells isolated from adult rat muscle differentiate across all three dermal lineages

Adult stem cells capable of differentiating into phenotypes from all three dermal layers were isolated from adult rat muscle. Stem cells were obtained by enzymatic digestion, followed by primary culture in Eagle's minimum essential medium +10% preselected horse serum. When the cells reached confluence, they were released by trypsin, filtered to remove differentiated myotubes, and then slow frozen in 7.5% dimethylsulfoxide to −80°C. Thawed cells were the stem cells and were induced to differentiate with the nonspecific differentiating agent dexamethasone at concentrations of 10−10–10−6 M. After a 6‐week treatment with dexamethasone, the cells were assayed by immunohistochemistry for phenotypes of the mesodermal, ectodermal, and endodermal lineages. Examples of mesodermal phenotypes identified were as follows: bone, cartilage, and skeletal, smooth, and cardiac muscle. Ectodermal phenotypes identified were as follows: neurons and oligodendrocytes. Hepatocyte phenotypes identified represented the endodermal lineage. All the phenotypes were observed only with treatment with dexamethasone. However, nestin was observed in the absence of dexamethasone and may be a marker for uncommitted pluripotent stem cells. The results show that adult muscle contains pluripotent stem cells capable of differentiating across all three dermal lineages. Such cells could be used in the context of tissue engineering.
Mouse Peg9/Dlk1 and human PEG9/DLK1 are paternally expressed imprinted genes closely located to the maternally expressed imprinted genes: mouse Meg3/Gtl2 and human MEG3

Genomic imprinting significantly influences development, growth and behaviour in mammals. Systematic screening of imprinted genes has been extensively carried out to identify the genes responsible for imprinted phenotypes and to elucidate the biological significance of this phenomenon. In this study, we applied DNA chip technology for isolating paternally expressed imprinted genes (Pegs). We compared the resulting expression profiles of parthenogenetic and fertilized control embryos to identify novel imprinted genes.
Polymicrobial Infection with Periodontal Pathogens Specifically Enhances MicroRNA miR-146a in ApoE−/− Mice during Experimental Periodontal Disease

ABSTRACT Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia are periodontal pathogens associated with the etiology of adult periodontitis as polymicrobial infections. Recent studies demonstrated that oral infection with P. gingivalis induces both periodontal disease and atherosclerosis in hyperlipidemic and proatherogenic ApoE−/− mice. In this study, we explored the expression of microRNAs (miRNAs) in maxillas (periodontium) and spleens isolated from ApoE−/− mice infected with P. gingivalis, T. denticola, and T. forsythia as a polymicrobial infection. miRNA expression levels, including miRNA miR-146a, and associated mRNA expression levels of the inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) were measured in the maxillas and spleens from mice infected with periodontal pathogens and compared to those in the maxillas and spleens from sham-infected controls. Furthermore, in response to these periodontal pathogens (as mono- and polymicrobial heat-killed and live bacteria), human THP-1 monocytes demonstrated similar miRNA expression patterns, including that of miR-146a, in vitro. Strikingly, miR-146a had a negative correlation with TNF-α secretion in vitro, reducing levels of the adaptor kinases IL-1 receptor-associated kinase 1 (IRAK-1) and TNF receptor-associated factor 6 (TRAF6). Thus, our studies revealed a persistent association of miR-146a expression with these periodontal pathogens, suggesting that miR-146a may directly or indirectly modulate or alter the chronic periodontal pathology induced by these microorganisms.
Design tradeoffs in a triode transconductor for low voltage zero-IF channel select filters

In this paper, we study the tradeoffs in operating the low voltage triode gm cell proposed by Enz at higher operating frequencies as a candidate for use in a zero-IF channel select filter. The tradeoffs in transconductor parameters are presented by introducing a current split factor design approach. It is determined that increasing the bias current in the feedback path increases the bandwidth of the gm cell at the expense of decreased tuning range and linear range. Results presented are simulated using a 0.35 µm digital CMOS process for a VDD of 1.8V. These are useful in the preliminary design of reconfigurable filters for multi-standard receivers.
SKELETAL TRAUMA WITH IMPLICATIONS FOR INTRATAIL MOBILITY IN EDMONTOSAURUS ANNECTENS FROM A MONODOMINANT BONEBED, LANCE FORMATION (MAASTRICHTIAN), WYOMING USA

Abstract: This study presents evidence of pre-mortem traumatic injury and its sequalae on multiple Edmontosaurus annectens skeletal elements recovered from a largely monodominant Cretaceous (Maastrichtian) bonebed. The sample consists of 3013 specimens excavated and prepared from two quarries, of which 96 elements manifest one or more macroscopic bone abnormalities and 55 specimens display pathology attributable to physical trauma. Evidence of traumatic pathology is strongly associated (P < .05) with body region, occurring disproportionately in the caudal vertebrae. Pre-mortem fractures with subsequent bone remodeling and hypertrophic ossification of caudal neural spines are present principally in the middle and mid-distal regions of the tail, while fractures of the vertebral centra are present primarily in the distal tail region. Other skeletal regions, such as chevrons, phalanges of the manus and ribs display unambiguous evidence of healed trauma, but with less frequency than the tail. These findings, in combination with current understanding of hadrosaurian tail biomechanics, indicate that intervertebral flexibility within the middle and mid-distal region of the tail likely rendered these caudal vertebrae more susceptible to the deleterious effects of repeated mechanical stress and subsequent trauma, potentially accompanying running locomotion and other high-impact herd interactions. Healed fractures within the region are also suggestive of accumulated injuries due to a combination of tail usage in defense and possibly accidental bumping/trampling associated with gregarious behavior.
Genetic diversity of norovirus, sapovirus, and astrovirus isolated from children hospitalized with acute gastroenteritis in Chiang Mai, Thailand

Norovirus (NV), sapovirus (SV), and human astrovirus (HAstV) are important causes of acute gastroenteritis in infants and young children. This study investigated the prevalence of NV, SV, and HAstV infections in children hospitalized with acute gastroenteritis in Chiang Mai, Thailand from May 2000 to March 2002. Fecal specimens were tested for NV, SV, and HAstV by reverse transcription polymerase chain reaction (RT‐PCR) using degenerate specific primers. These viruses were characterized further by sequence and phylogenetic analyses of the partial capsid gene. From 296 fecal specimens tested, 13.5% (40 of 296) were positive for NV, SV, and HAstV. Of these, NV most predominant, with a prevalence of 60% (24 of 40), of which 17.5% were NVGI and 42.5% were NVGII. Of note, one specimen was positive for both NVGI and SV. SV was detected in 25%, while HAstV was detected in 17.5%. Analysis of nucleotide and amino acid sequences revealed that NVGI strains comprised GI/3, GI/4, GI/6, GI/7, and GI/13 genotypes. Among NVGII strains, approximately half of them belonged to genotype GII/4 (Lordsdale virus cluster), followed by GII/3, GII/10, GII/1, GII/6, GII/8, and GII/15. Analysis of SV sequences revealed that SVGI (Manchester virus) was more common than SVGII (London virus). The SV genotypes detected in this study belonged to SVGI/1, SVGI/4, SVGI/5, SVGII/1, and SVGII/2, whereas the HAstV belonged to genotypes HAstV‐1, HAstV‐2, HAstV‐3, and HAstV‐5. The findings suggest that NV, SV, and HAstV are important enteric viruses cocirculating among hospitalized children in Chiang Mai, Thailand. J. Med. Virol. 80:1749–1755, 2008. © 2008 Wiley‐Liss, Inc.
Usefulness and limitations of ultrasound‐guided core biopsy in the diagnosis of musculoskeletal tumours

Ultrasound‐guided needle biopsy is a safe and efficient diagnostic method increasingly used in the initial approach to superficial and deep musculoskeletal tumours. However, so far no general consensus has been reached regarding its reliability. During a 6‐year period (1999–2004), biopsies were taken from 188 patients (100 females, 88 males; age average 55.8 years) with musculoskeletal tumours under ultrasound guidance using 18G BioPince® or 14G ProMag® 2.2 true‐cut type needles. Cytological (imprints and cytocentrifugates) and histological material was obtained for diagnosis in every case. The lower extremity (59 cases) and the abdominal wall (29 cases) were the most commonly affected sites. Benign/reactive tumours (77 cases), metastatic epithelial malignancies (40 cases), and sarcomas (36 cases) were most frequently diagnosed. In 180 (95.75%) cases, core needle results were concordant with the definitive diagnosis (97 true positives and 83 true negatives). Relevant diagnostic discordance was seen in 8 (4.25%) cases (8 false negatives and 0 false positives). Sensitivity, specificity and positive and negative predictive values were 92%, 100%, 100%, and 91%, respectively. Ultrasound‐guided core biopsy is thus a useful method in the initial approach to musculoskeletal tumours that allows correct patient management in the vast majority of cases.
A novel histone H4 mutant defective in nuclear division and mitotic chromosome transmission

The histone proteins are essential for the assembly and function of th e eukaryotic chromosome. Here we report the first isolation of a temperature-sensitive lethal histone H4 mutant defective in mitotic chromosome transmission Saccharomyces cerevisiae. The mutant requires two amino acid substitutions in histone H4: a lethal Thr-to-Ile change at position 82, which lies within one of the DNA-binding surfaces of the protein, and a substitution of Ala to Val at position 89 that is an intragenic suppressor. Genetic and biochemical evidence shows that the mutant histone H4 is temperature sensitive for function but not for synthesis, deposition, or stability. The chromatin structure of 2 micrometer circle minichromosomes is temperature sensitive in vivo, consistent with a defect in H4-DNA interactions. The mutant also has defects in transcription, displaying weak Spt- phenotypes. At the restrictive temperature, mutant cells arrest in the cell cycle at nuclear division, with a large bud, a single nucleus with 2C DNA content, and a short bipolar spindle. At semipermissive temperatures, the frequency of chromosome loss is elevated 60-fold in the mutant while DNA recombination frequencies are unaffected. High-copy CSE4, encoding an H3 variant related to the mammalian CENP-A kinetochore antigen, was found to suppress the temperature sensitivity of the mutant without suppressing the Spt- transcription defect. These genetic, biochemical, and phenotypic results indicate that this novel histone H4 mutant defines one or more chromatin-dependent steps in chromosome segregation.