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At least 433 records · Page 24Linked to original sources
PubMed2002

Oblimersen Bcl-2 antisense: facilitating apoptosis in anticancer treatment.

The components of the apoptotic program are targets for anticancer therapy. Bcl-2 protein inhibits apoptosis and confers resistance to treatment with traditional cytotoxic chemotherapy, radiotherapy, and monoclonal antibodies (mAb). Oblimersen sodium (G3139, Genasense, Genta Inc., Berkeley Heights, NJ) is an antisense oligonucleotide (AS-ON) compound designed to specifically bind to the first 6 codons of the human bcl-2 mRNA sequence, resulting in degradation of bcl-2 mRNA and subsequent decrease in Bcl-2 protein translation. Oblimersen is the first oligonucleotide to demonstrate proof of principle of an antisense effect in human tumors by the documented downregulation of the target Bcl-2 protein. A growing body of preclinical and clinical evidence suggests that oblimersen synergizes with many cytotoxic and biologic/immunotherapeutic agents against a variety of hematologic malignancies and solid tumors. Randomized clinical trials are currently underway to evaluate the efficacy and tolerability of oblimersen in combination with cytotoxic chemotherapy in chronic lymphocytic leukemia, multiple myeloma, malignant melanoma, and non-small cell lung cancer. In addition, nonrandomized trials are under way to evaluate oblimersen in non-Hodgkin's lymphoma, acute myeloid leukemia, and hormone-refractory prostate cancer. Preclinical data also support the clinical evaluation of oblimersen in additional tumor types, including chronic myelogenous leukemia and breast, small cell lung, gastric, colon, bladder, and Merkel cell cancers. Enhancement of the efficacy of anticancer treatments with oblimersen Bcl-2 antisense therapy represents a promising new apoptosis-modulating strategy, and ongoing clinical trials will test this therapeutic approach.

Antineoplastic Agents↗
PubMed2004

Early stages of the secretory pathway, but not endosomes, are required for Cvt vesicle and autophagosome assembly in Saccharomyces cerevisiae.

The Cvt pathway is a biosynthetic transport route for a distinct subset of resident yeast vacuolar hydrolases, whereas macroautophagy is a nonspecific degradative mechanism that allows cell survival during starvation. Yet, these two vacuolar trafficking pathways share a number of identical molecular components and are morphologically very similar. For example, one of the hallmarks of both pathways is the formation of double-membrane cytosolic vesicles that sequester cargo before vacuolar delivery. The origin of the vesicle membrane has been controversial and various lines of evidence have implicated essentially all compartments of the endomembrane system. Despite the analogies between the Cvt pathway and autophagy, earlier work has suggested that the origin of the engulfing vesicle membranes is different; the endoplasmic reticulum is proposed to be required only for autophagy. In contrast, in this study we demonstrate that the endoplasmic reticulum and/or Golgi complex, but not endosomal compartments, play an important role for both yeast transport routes. Along these lines, we demonstrate that Berkeley bodies, a structure generated from the Golgi complex in sec7 cells, are immunolabeled with Atg8, a structural component of autophagosomes. Finally, we also show that none of the yeast t-SNAREs are located at the preautophagosomal structure, the presumed site of double-membrane vesicle formation. Based on our results, we propose two models for Cvt vesicle biogenesis.

Aminopeptidases↗
PubMed2002

Factors associated with oxidative stress in human populations.

Oxidation of biomolecules may play a role in susceptibility to a number of diseases. However, there are few large-scale survey data describing oxidative damage that occurs in humans and the demographic, physical, or nutritional factors that may be associated with it. Such information is essential for the design and analysis of studies investigating the role of oxidative stress in health and disease. This paper presents data on levels of two biomarkers of lipid peroxidation, malondialdehyde and F(2)-isoprostanes, in 298 healthy adults aged 19-78 years. The study was conducted in Berkeley and Oakland, California, in 1998-1999. Sex was the strongest predictor of lipid peroxidation as measured by both biomarkers (p < 0.0001); it was stronger than smoking. C-reactive protein was positively associated with lipid peroxidation (p = 0.004), as was plasma cholesterol. Plasma ascorbic acid had a strong inverse relation (p < 0.001) with both biomarkers. Plasma beta-carotene was also associated with F(2)-isoprostanes. Other plasma antioxidants were not associated with lipid peroxidation biomarkers, once ascorbic acid was included in the multivariate model. Future surveys and epidemiologic studies should measure at least one marker of oxidative damage, as well as plasma ascorbic acid. These data would permit a better understanding of the role that oxidants and antioxidants play in the health of human populations.

Adult↗
PubMed2003

Accuracy of fetal growth indicators as surrogate measures of steroid hormone levels during pregnancy.

This study evaluates the use of fetal growth characteristics as surrogate measures for steroid hormone exposures during pregnancy. The validity of using birth weight, birth length, ponderal index, and placental weight as indicators of pregnancy hormone exposures was assessed using third-trimester serum samples from 568 pregnant women who participated in the Child Health and Development Studies, Berkeley, California (1959-1966). The magnitude of the associations between birth characteristics and hormone concentrations was assessed using geometric means, Pearson's correlations, and linear and logistic regression. Accuracy was evaluated using sensitivity, specificity, and receiver operating characteristic curve analyses. The strongest and most consistent association observed was between birth weight and estriol levels. Despite a positive correlation (r = 0.32) and strong associations with high estriol levels (odds ratio for highest compared with lowest birth weight quartile = 6.63, 95% confidence interval: 3.20, 12.5), the predictive performance of birth weight as a proxy for estriol levels was poor (area under the receiver operating characteristic curve = 0.66, 95% confidence interval: 0.61, 0.71). Likewise, all fetal growth measures revealed little discriminatory ability as indicators of estriol, estrone, estradiol, or progesterone levels. Thus, observed associations with these surrogate measures may not be a reflection of pregnancy hormone exposure and should be interpreted with caution.

Biomarkers↗
PubMed2003

The Drosophila melanogaster genome sequencing and annotation projects: a status report.

The sequence and genome annotations of Drosophila melanogaster were initially published in late 1999 and early 2000. Since then, the Berkeley Drosophila Genome Project (BDGP) and FlyBase have improved the quality of the sequence and reviewed the annotations by hand, respectively, to produce an account of the fruit fly genome that is of the highest quality. This review discusses the main features of this process, both from the point of view of the biology revealed in the end result and in the development of software that has been central to this genome sequencing and annotation project.

Animals↗
PubMed2002

VIZARD: analysis of Affymetrix Arabidopsis GeneChip data.

UNLABELLED: The Affymetrix GeneChip Arabidopsis genome array has proved to be a very powerful tool for the analysis of gene expression in Arabidopsis thaliana, the most commonly studied plant model organism. VIZARD is a Java program created at the University of California, Berkeley, to facilitate analysis of Arabidopsis GeneChip data. It includes several integrated tools for filtering, sorting, clustering and visualization of gene expression data as well as tools for the discovery of regulatory motifs in upstream sequences. VIZARD also includes annotation and upstream sequence databases for the majority of genes represented on the Affymetrix Arabidopsis GeneChip array. AVAILABILITY: VIZARD is available free of charge for educational, research, and not-for-profit purposes, and can be downloaded at http://www.anm.f2s.com/research/vizard/ CONTACT: moseyko@uclink4.berkeley.edu

Arabidopsis↗
PubMed2004

Phylogenomic inference of protein molecular function: advances and challenges.

MOTIVATION: Protein families evolve a multiplicity of functions through gene duplication, speciation and other processes. As a number of studies have shown, standard methods of protein function prediction produce systematic errors on these data. Phylogenomic analysis--combining phylogenetic tree construction, integration of experimental data and differentiation of orthologs and paralogs--has been proposed to address these errors and improve the accuracy of functional classification. The explicit integration of structure prediction and analysis in this framework, which we call structural phylogenomics, provides additional insights into protein superfamily evolution. RESULTS: Results of protein functional classification using phylogenomic analysis show fewer expected false positives overall than when pairwise methods of functional classification are employed. We present an overview of the motivations and fundamental principles of phylogenomic analysis, new methods developed for the key tasks, benchmark datasets for these tasks (when available) and suggest procedures to increase accuracy. We also discuss some of the methods used in the Celera Genomics high-throughput phylogenomic classification of the human genome. AVAILABILITY: Software tools from the Berkeley Phylogenomics Group are available at http://phylogenomics.berkeley.edu

Algorithms↗
PubMed2005

The fragment assembly string graph.

We present a concept and formalism, the string graph, which represents all that is inferable about a DNA sequence from a collection of shotgun sequencing reads collected from it. We give time and space efficient algorithms for constructing a string graph given the collection of overlaps between the reads and, in particular, present a novel linear expected time algorithm for transitive reduction in this context. The result demonstrates that the decomposition of reads into kmers employed in the de Bruijn graph approach described earlier is not essential, and exposes its close connection to the unitig approach we developed at Celera. This paper is a preliminary piece giving the basic algorithm and results that demonstrate the efficiency and scalability of the method. These ideas are being used to build a next-generation whole genome assembler called BOA (Berkeley Open Assembler) that will easily scale to mammalian genomes.

Algorithms↗
PubMed2000

A developmental model applied to problems of deafness.

From the Editors: This article represents another in our series of "classics" that helped to shape the field of deaf studies and deaf education. The article first appeared as Chapter Two in Sound and Sign: Childhood Deafness and Mental Health, H. S. Schlesinger and K. P. Meadow (1972), Berkeley: University of California Press. The book reported pioneering research and clinical mental health services at the Langley Porter Neuropsychiatric Institute, University of California, San Francisco. For current readers, some of the language may seem out of date, and the Editors have made several minor modifications to ensure that readers fully recognize the original intention of the author. (Such modifications are indicated by square brackets or ellipses for contemporary purposes, but the intentions of the original all have been maintained, and Editors' notes are indicated as such to distinguish them from the Authors' notes.) Nevertheless, many of the ideas are fresh and important. Indeed, some passages serve as particular reminders of significant changes in opportunities for and attitudes about Deaf people over the past three decades. Many of these changes resulted directly from the work of Dr. Schlesinger and her colleagues.

Journal Article↗
PubMed2001

Mapping and identification of essential gene functions on the X chromosome of Drosophila.

The Drosophila melanogaster genome consists of four chromosomes that contain 165 Mb of DNA, 120 Mb of which are euchromatic. The two Drosophila Genome Projects, in collaboration with Celera Genomics Systems, have sequenced the genome, complementing the previously established physical and genetic maps. In addition, the Berkeley Drosophila Genome Project has undertaken large-scale functional analysis based on mutagenesis by transposable P element insertions into autosomes. Here, we present a large-scale P element insertion screen for vital gene functions and a BAC tiling map for the X chromosome. A collection of 501 X-chromosomal P element insertion lines was used to map essential genes cytogenetically and to establish short sequence tags (STSs) linking the insertion sites to the genome. The distribution of the P element integration sites, the identified genes and transcription units as well as the expression patterns of the P-element-tagged enhancers is described and discussed.

Animals↗
PubMed1994

Genetic variation of the repeated MAL loci in natural populations of Saccharomyces cerevisiae and Saccharomyces paradoxus.

In Saccharomyces cerevisiae, the gene functions required to ferment the disaccharide maltose are encoded by the MAL loci. Any one of five highly sequence homologous MAL loci identified in various S. cerevisiae strains (called MAL1, 2, 3, 4 and 6) is sufficient to ferment maltose. Each is a complex of three genes encoding maltose permease, maltase and a transcription activator. This family of loci maps to telomere-linked positions on different chromosomes and most natural strains contain more than one MAL locus. A number of naturally occurring, mutant alleles of MAL1 and MAL3 have been characterized which lack one or more of the gene functions encoded by the fully functional MAL loci. Loss of these gene functions appears to have resulted from mutation and/or rearrangement within the locus. Studies to date concentrated on the standard maltose fermenting strains of S. cerevisiae available from the Berkeley Yeast Stock Center collection. In this report we extend our genetic analysis of the MAL loci to a number of maltose fermenting and nonfermenting natural strains of S. cerevisiae and Saccharomyces paradoxus. No new MAL loci were discovered but several new mutant alleles of MAL1 were identified. The evolution of this gene family is discussed.

Alleles↗
PubMed1996

Zygotic lethal mutations with maternal effect phenotypes in Drosophila melanogaster. II. Loci on the second and third chromosomes identified by P-element-induced mutations.

Screens for zygotic lethal mutations that are associated with specific maternal effect lethal phenotypes have only been conducted for the X chromosome. To identify loci on the autosomes, which represent four-fifths of the Drosophila genome, we have used the autosomal "FLP-DFS" technique to screen a collection of 496 P element-induced mutations established by the Berkeley Drosophila Genome Project. We have identified 64 new loci whose gene products are required for proper egg formation or normal embryonic development.

Animals↗
PubMed2001

Ras1 interacts with multiple new signaling and cytoskeletal loci in Drosophila eggshell patterning and morphogenesis.

Little is known about the genes that interact with Ras signaling pathways to regulate morphogenesis. The synthesis of dorsal eggshell structures in Drosophila melanogaster requires multiple rounds of Ras signaling followed by dramatic epithelial sheet movements. We took advantage of this process to identify genes that link patterning and morphogenesis; we screened lethal mutations on the second chromosome for those that could enhance a weak Ras1 eggshell phenotype. Of 1618 lethal P-element mutations tested, 13 showed significant enhancement, resulting in forked and fused dorsal appendages. Our genetic and molecular analyses together with information from the Berkeley Drosophila Genome Project reveal that 11 of these lines carry mutations in previously characterized genes. Three mutations disrupt the known Ras1 cell signaling components Star, Egfr, and Blistered, while one mutation disrupts Sec61beta, implicated in ligand secretion. Seven lines represent cell signaling and cytoskeletal components that are new to the Ras1 pathway; these are Chickadee (Profilin), Tec29, Dreadlocks, POSH, Peanut, Smt3, and MESK2, a suppressor of dominant-negative Ksr. A twelfth insertion disrupts two genes, Nrk, a "neurospecific" receptor tyrosine kinase, and Tpp, which encodes a neuropeptidase. These results suggest that Ras1 signaling during oogenesis involves novel components that may be intimately associated with additional signaling processes and with the reorganization of the cytoskeleton. To determine whether these Ras1 Enhancers function upstream or downstream of the Egf receptor, four mutations were tested for their ability to suppress an activated Egfr construct (lambdatop) expressed in oogenesis exclusively in the follicle cells. Mutations in Star and l(2)43Bb had no significant effect upon the lambdatop eggshell defect whereas smt3 and dock alleles significantly suppressed the lambdatop phenotype.

Animals↗
PubMed1997

Wisdom and life satisfaction in old age.

According to previous research findings, objective life conditions such as physical health, socioeconomic status, financial situation, the physical environment, and social involvement cannot fully explain the well-being of older persons. Instead, personality characteristics and developmental influences appear to have a stronger impact. This study combines personality and individual development by introducing the ancient but neglected concept of wisdom as a predictor of life satisfaction. Using a sample of 120 elderly women and men from the 1968/69 Berkeley Guidance Study, structural equation models with latent variables show that wisdom (defined aa a composite of cognitive, reflective, and effective qualities) has a profoundly positive influence on life satisfaction independent of objective circumstances. The inclusion of wisdom as an additional predictor of subjective well-being increases the explanatory power of the model considerably. Gender differences in predictors of life satisfaction are discussed.

Affect↗
PubMed1982

Early adult antecedents of life satisfaction at age 70.

Association between Life Satisfaction Ratings at about age 70 and cognitive, personality, interpersonal, and family characteristics in early adulthood are examined using data from the Guidance Study at the University of California, Berkeley. When the parents of participants in that study were in their early 30s, the mothers were rated on 15 cognitive and personality characteristics and both parents were rated on personal, interpersonal, and family variables. Approximately 40 years later, the surviving parents were interviewed intensively and assigned Life Satisfaction Ratings, For both sexes, certain traits of their own at 30 are correlated with life satisfaction at 70. The predictive characteristics for women reflect a buoyant, responsive attitude toward life; those for men represent emotional and physical health. For a woman, the material relationship and some of her circumstances at 30 were also predictive, but her husband's traits were for the most part unrelated to her satisfaction with life at 70. For men, in contrast, characteristics of their wives indicative of emotional stability were even more highly predictive of their life satisfaction at 70 than were their own traits at 30.

Aged↗
PubMed1988

Continuity and change in social support between young-old and old-old or very-old age.

This longitudinal research examined continuity and change in social support in a sample of 74 old-old (74 to 84) or very-old (85 and over) members of the Berkeley Older Generation Study. Considerable continuity in extent of contact was found between 1969 and 1983 for the group as a whole, particularly with respect to family relationships. In beyond-family contacts, declines were observed for men but not women, and for the very-old but not the old-old. Important changes also were observed in involvement or subjective level of commitment: satisfaction with children increased, while involvement beyond the family declined.

Adult↗
PubMed1993

The influence of health on family contacts and family feelings in advanced old age: a longitudinal study.

This study provides a longitudinal analysis of the influences of health, age, gender, and socioeconomic status on family contacts and family feelings in a sample of 62 members of the Berkeley Older Generation Study. Stability in family contacts and in family feelings was observed over 14 years of advanced old age. Of the four predictor variables, health and socioeconomic status accounted for the largest proportion of observed variance. Contrary to our hypotheses, study participants in better health had greater amounts of contact with family than did those in poorer health. The former also had more feelings of closeness to family members, a finding that may reflect greater possibilities for reciprocity between elders in good health and their family members.

Activities of Daily Living↗
PubMed2005

Identification and partial characterization of the enzyme of omega: one of five putative DPP IV genes in Drosophila melanogaster.

The omega (ome) gene product is a modifier of larval cuticle protein 5 and its alleles (and duplicates) in the third instar of Drosophila melanogaster. Using deletion mapping the locus mapped to 70F-71A on the left arm of chromosome 3. A homozygote null mutant (ome 1) shows a pleiotropic phenotype that affected the size, developmental time of the flies, and the fertility (or perhaps the behavior) of homozygous mutant males. The omega gene was verified as producing a dipeptidyl peptidase IV (DPPIV) by genetic analysis, substrate specificity and pH optimum. The identity of the gene was confirmed as CG32145 (cytology 70F4) in the Celera Database (Berkeley Drosophila Genome Project), which is consistent with its deletion map position. The genomic structure of the gene is described and the decrease in DPPIV activity in the mutant ome1 is shown to be due to the gene CG32145 (omega). The D. melanogaster omega DPPIV enzyme was partially purified and characterized. The exons of the ome1 mutant were sequenced and a base substitution mutation in exon 4 was identified that would yield a truncated protein caused by a stop codon. A preliminary study of the compartmentalization of the omega DPPIV enzyme in several organs is also reported.

Amino Acid Sequence↗