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At least 1,279 records · Page 71Linked to original sources
PubMed2005

Wax constituents on the inflorescence stems of double eceriferum mutants in Arabidopsis reveal complex gene interactions.

To shed new light on gene involvement in plant cuticular-wax production, 11 eceriferum (cer) mutants of Arabidopsis having dramatic alterations in wax composition of inflorescence stems were used to create 14 double cer mutants each with two homozygous recessive cer loci. A comprehensive analysis of stem waxes on these double mutants revealed unexpected CER gene interactions and new ideas about individual CER gene functions. Five of the 14 double cer mutants produced significantly more total wax than one of their respective cer parents, indicating from a genetic standpoint a partial bypassing (or complementation) of one cer mutation by the other. Eight of the 14 double cer mutants had alkane amounts lower than both respective cer parents, suggesting that most of these CER gene products play a major additive role in alkane synthesis. Other results suggested that some CER genes function in more than one step of the wax pathway, including those associated with sequential steps in acyl-CoA elongation. Surprisingly, complete epistasis was not observed for any of the cer gene combinations tested. Significant overlap or redundancy of genetic operations thus appears to be a central feature of wax metabolism. Future studies of CER gene product function, as well as the utilization of CER genes for crop improvement, must now account for the complex gene interactions described here.

Arabidopsis↗
PubMed2006

Quantitative profiling of polar glycerolipid species from organs of wild-type Arabidopsis and a phospholipase Dalpha1 knockout mutant.

Lipid profiling is a targeted metabolomics platform that provides a comprehensive analysis of lipid species with high sensitivity. Profiling based on electrospray ionization tandem mass spectrometry (ESI-MS/MS) provides quantitative data and is adaptable to high throughput analyses. Here we report the profiling of 140 apparent molecular species of polar glycerolipids in Arabidopsis leaves, flower stalks, flowers, siliques, roots, and seeds. Considerable differences in lipid species occur among these organs, providing insights into the different lipid metabolic activities in a specific organ. In addition, comparative profiling between wild-type and a knockout mutant pldalpha1 (locus ID: AT3G15730) provides insight into the metabolic function of phospholipase D (PLD) in different organs. PLDalpha1 contributes significantly to phosphatidic acid (PA) levels in roots, seeds, flowers, and flower stalks, but little to basal PA levels in siliques and leaves. In seeds of the pldalpha1 mutant plants, levels of PA, lysophosphatidylcholine, and lysophosphatidylethanolamine were significantly lower than those of wild-type seeds, suggesting a role for PLDalpha1 in membrane lipid degradation in seeds.

Arabidopsis↗
PubMed2005

Identification of tobacco ESTs with a hypersensitive response (HR)-specific pattern of expression and likely involved in the induction of the HR and/or localized acquired resistance (LAR).

Plant defense responses against pathogens often involve the restriction of the pathogen to its site of penetration. Restriction is achieved through the combined effects of the hypersensitive response (HR) and its tightly connected localized acquired resistance (LAR). As LAR is induced by unknown signals released by the cells undergoing the HR, LAR inducing/regulating genes must show a HR-specific pattern of expression. Here, we describe a differential display reverse-transcript polymerase chain reaction (DDRT-PCR) strategy to isolate tobacco expressed sequence tags (ESTs) characterized by such an expression profile, which also characterizes genes involved in the induction/execution of the HR. We compared the DDRT-PCR profile of tobacco cell suspensions treated with beta-megaspermin inducing the HR with that of untreated cells and cells treated with alpha-megaspermin inducing a Defense No Death (DND) phenotype. The expression profile of the selected ESTs was analyzed in tobacco plants expressing a beta-megaspermin-induced HR or a DND phenotype, including LAR, induced by three different elicitors. This comprehensive analysis allowed to identify 24 HR-specific ESTs, half of them shows no or non-significant homology with ESTs and genes in the databases. The other half exhibits homology with genes encoding a receptor-like kinase protein, proteins involved in the regulation of plasma membrane structure, proteins of the ubiquitin/26S proteasome proteolytic system, RNA binding proteins, and a protein hypothesized to be a true regulator of the HR.

Expressed Sequence Tags↗
PubMed2006

Treatment-refractory obsessive-compulsive disorder: methodological issues, operational definitions and therapeutic lines.

While controlled trials with SRIs have demonstrated a selective efficacy in obsessive-compulsive disorder (OCD), up to 40-60% of patients do not have a satisfactory outcome. Non-response to treatment in OCD is associated with serious social disability. There are a large number of non-responsive patients, and they are difficult to cluster due to ambiguities in diagnostic criteria, possibility of subtypes and a high rate of comorbidity. Moreover, the findings of current studies of "so-called" non-responsive cases are currently non-generalizable because of the lack of an operational definition of non-response. The result has been that a cumulative body of data on a reasonably homogeneous sample of non-responders has not been developed. The aims of the research in this area are to clarify some of the obstacles in defining stages of response and levels of non-response and, through a comprehensive analysis, to propose a systematic nosology for this rather common condition. Better characterization of which patients respond and do not respond to various treatments will enable more accurate clustering of patients, and help facilitate multisite data collection for future research trials. The authors reviewed also the more recent therapeutic pharmacological and psychological lines for the treatment of refractoriness in OCD.

Combined Modality Therapy↗
PubMed2005

Mangrove health in an arid environment encroached by urban development--a case study.

Urban development will soon encroach upon several protected and largely unspoiled arid climate mangroves ecosystems located along the lagoon called Ensenada de La Paz in Baja California Sur, Mexico. Many of these mangroves are located on a large sandbar that separates the lagoon on the south side from Bahía de La Paz to the north. A general evaluation of the current status of these mangroves was conducted to establish biological and physicochemical indicators of the health of these mangroves to serve as a natural or predevelopment baseline in future management. The following parameters were measured in the feeding channels of the mangroves and at the mouth of the channels: vegetation coverage, species and health, and levels of dissolved oxygen, pH, salinity, total nitrogen, ammonium, nitrates and nitrites, phosphorus ions, and organic matter in sediments and seawater. The microbiological elements that were studied included aerobic bacteria, N2-fixing bacteria, inorganic phosphate solubilizers, coliform, and phytoplankton diversity. Bird populations were counted, with special attention to migratory and resident birds and protected and endangered species. A comprehensive analysis of all the elements indicated that the health of the sandbar mangrove populations is good despite the proximity of a modest urban center. It also demonstrated that several biological and physicochemical parameters used in this study, including the birds, can serve as indicators of mangrove health and as a baseline for future management of mangroves in regions with arid climates.

Journal Article↗
PubMed2003

Divergence and complexities in DAG signaling: looking beyond PKC.

For many years protein kinase C (PKC) has been the subject of extensive studies as a molecular target for the treatment of cancer and other diseases. To better define the role of PKC isozymes in the control of cell proliferation, survival and transformation, the examination of PKC-mediated signal transduction pathways by isozyme-specific intervention has become essential. However, issues related to the selectivity of activators and inhibitors of PKC isozymes, in addition to convoluted cross-talks between phorbol ester-regulated pathways, have greatly complicated our understanding of PKC-mediated responses. An additional level of complexity is provided by the fact diacylglycerol (DAG) signals can be transduced by phorbol ester receptors other than PKC. These receptors include chimaerins, RasGRPs, MUNC13s, PKD (PKC mu) and DAG kinases beta and gamma. Thus, it is conceivable that some of the effects that were originally attributed to PKC isozymes in response to phorbol esters might be mediated by PKC-independent pathways. A key issue for the design of novel therapeutic strategies that target PKC isozymes is a comprehensive analysis of isozyme-specific signal transduction pathways in different cell types and the development of pharmacological and molecular tools that can distinguish between the various PKC and 'non-PKC' phorbol ester receptors.

Diglycerides↗
PubMed2006

Male killers and the origins of paternal genome elimination.

The haploidizing male killer hypothesis suggests an evolutionary origin for paternal genome elimination (PGE) that is consistent with the ecological correlates of ancestral haplodiploid insect clades. We make use of population genetics models to test the logic and assumptions of this hypothesis with particular emphasis on the co-evolution between bacteria and host. We derive simple invasion conditions for rare modifiers of bacteria transmission and rare modifiers of host survivorship after haploidization. We also study the evolutionary dynamics of both these modifiers. We conclude that PGE shows evolutionary genetic stability and present a comprehensive analysis of the probability that such genetic system evolves due to the action of cytoplasmic genes.

Animals↗
PubMed2006

Reassortment between human A(H3N2) viruses is an important evolutionary mechanism.

Phylogenetic relationships of whole genomes of H3N2 viruses circulating in Germany during a 6-year period from 1998 to 2005 revealed the co-circulation of different lineages of viruses. Multiple reassortment events occurred during this time between viruses belonging to different lineages or different subgroups. Strains isolated during 1998-1999 were characterised by a surprisingly high heterogeneity and multiple reassortment events. Seventy percent of the examined 1998-1999 viruses had completely different genome compositions. To our knowledge, such an exceptional high proportion of different reassortant strains, encompassing all eight genome segments, have not been described before. In contrast, only one reassortant virus was prevalent during 1999-2000 even though two of the three 1998-1999 lineages were co-circulating. Reassortant viruses were isolated also in each of the other seasons. However, the proportion of H3N2 viruses with different genome compositions varied from season to season. Strains with a reassortant NA played an important role and were also detected during 2003-2004 and 2004-2005 accounting for 45% and 70% of the circulating H3N2 viruses, respectively. Moreover, different reassortment events occurring during these seasons included also the PB1, PB2 and NP genes. The results presented here emphasize that genetic reassortment is an important factor in the evolution of H3N2 viruses and highlight the need for a comprehensive analysis of influenza viruses, especially with regard to the annual vaccine composition.

Biological Evolution↗
PubMed2025

Structural diversity and evolutionary constraints of oxidative phosphorylation.

The oxidative phosphorylation (OxPhos) system is central to metabolism. The more than 90 structural subunits are encoded by different chromosome categories (autosomal, X, and mtDNA). The system is envisioned as an invariant structure between cells and individuals. However, a comprehensive analysis of the 1,000 Genomes Project data reveals unexpected genetic intra-individual variability resulting from the heterozygosity of diploid autosomal genes, while diversity at the population level is generated by variability in mtDNA. We characterized the different levels of structural constriction at evolutionary and population levels for all OxPhos protein residues. To support this analysis, we developed ConScore, a conservation-based predictor of variant impact within OxPhos proteins (area under the receiver operating characteristic curve [ROC-AUC] = 0.97; area under the precision-recall curve [PR-AUC] = 0.94). Notably, for the nuclear-encoded subunits, we found mechanisms limiting individual variability as allelic imbalance or homozygosity bias. Integrating structural, functional, and genetic data, we highlight the significance of each OxPhos protein position, expanding insights into its role in speciation and disease.

Oxidative Phosphorylation↗
PubMed2004

Expression profiles of 39 HOX genes in normal human adult organs and anaplastic thyroid cancer cell lines by quantitative real-time RT-PCR system.

HOX genes are well known as master control genes in embryonic morphogenesis. We hypothesized that HOX genes give cells spatial information to maintain tissue- or organ-specificity in adult body and that the deregulated expression of HOX genes results in tumor development. We established a comprehensive analysis system to quantify expression of 39 human HOX genes based on the real-time reverse transcription PCR (RT-PCR) method. Analysis of 39 HOX genes of 20 normal adult organs by this system revealed that 5' HOX genes were expressed in organs in the caudal parts of the body, and that the more caudal regions the more numbers of HOX genes were expressed. It was also found that the expression patterns of HOX genes were more similar in the adjacent genes on the same cluster rather than in those belonging to the same paralogs. Compared with normal thyroid tissues, thyroid cancer cell lines showed the altered expression of some HOX genes, especially Abd-B homeobox family genes. Our results showed that HOX genes were organ-specifically expressed in adult body and that the deregulated expressions of Abd-B family genes were implicated in thyroid tumor development.

Actins↗
PubMed2004

Mutation and expression of the TP53 gene in early stage epithelial ovarian carcinoma.

OBJECTIVE: The early natural history of epithelial ovarian carcinoma remains poorly understood. Mutation of the TP53 gene is common in advanced-stage (III-IV) ovarian cancers, but less well described in early stage (I-II) tumors. The purpose of this study was to perform a comprehensive analysis of TP53 mutation and p53 expression status in early stage ovarian carcinomas. METHODS: Seventy-three cases of various histologic types, including 46 stage I and 27 stage II tumors, were subjected to direct sequence analysis of the entire TP53 coding region and exon-intron junctions as well as immunohistochemical assessment of p53 expression. RESULTS: Overall, mutations were identified in 24 of 73 (34%) cases. However, a significant difference in the distribution of mutations among histologic types was observed; TP53 mutations were present in 14 of 21 (67%) serous cancers and 11 of 52 (21%) non-serous cancers (P = 0.0002). Mutations were equally common between stage I and stage II tumors of serous histology. With respect to the correlation between TP53 mutation and p53 immunopositivity, the sensitivity (58%), specificity (71%), positive predictive value (64%), and negative predictive value (83%) were not sufficiently robust to justify use of p53 expression as a surrogate or screen for mutation. CONCLUSIONS: These data indicate that TP53 mutation is common in early stage ovarian carcinomas of serous histology, with a mutation frequency comparable to that reported for advanced-stage tumors, and is therefore likely to occur early in the progression of the most common histologic variant of ovarian carcinoma.

Epithelial Cells↗
PubMed2006

Regulation of cardiomyocyte signaling by RGS proteins: differential selectivity towards G proteins and susceptibility to regulation.

Many signals that regulate cardiomyocyte growth, differentiation and function are mediated via heterotrimeric G proteins, which are under the control of RGS proteins (Regulators of G protein Signaling). Several RGS proteins are expressed in the heart, but so far little is known about their function and regulation. Using adenoviral gene transfer, we conducted the first comprehensive analysis of the capacity and selectivity of the major cardiac RGS proteins (RGS2-RGS5) to regulate central G protein-mediated signaling pathways in adult ventricular myocytes (AVM). All four RGS proteins potently inhibited Gq/11-mediated phospholipase C beta stimulation and cell growth (assessed in neonatal myocytes). Importantly, RGS2 selectively inhibited Gq/11 signaling, whereas RGS3, RGS4 and RGS5 had the capacity to regulate both Gq/11 and Gi/o signaling (carbachol-induced cAMP inhibition). Gs signaling was unaffected, and, contrary to reports in other cell lines, RGS2-RGS5 did not appear to regulate adenylate cyclase directly in AVM. Since RGS proteins can be highly regulated in their expression by many different stimuli, we also tested the hypothesis that RGS expression is subject to G protein-mediated regulation in AVM and determined the specificity with which enhanced G protein signaling alters endogenous RGS expression in AVM. RGS2 mRNA and protein were markedly but transiently up-regulated by enhanced Gq/11 signaling (alpha1-adrenergic stimulation or Galphaq* overexpression), possibly by a negative feedback mechanism. In contrast, the other negative regulators of Gq/11 signaling (RGS3-RGS5) were unchanged. Endogenous RGS2 (but not RGS3-RGS5) expression was also up-regulated in cells with enhanced AC signaling (beta-adrenergic or forskolin stimulation). Taken together, these findings suggest diverse roles of RGS proteins in regulating myocyte signaling. RGS2 emerged as the only selective and highly regulated inhibitor of Gq/11 signaling that could potentially become a promising target for ameliorating Gq/11-mediated signaling and growth.

Adenoviridae↗
PubMed2004

Microarrayed allergens for IgE profiling.

Diagnosis of type I allergy is based on anamnesis, provocation testing, and serological determination of total and specific IgE. Currently, in vivo and in vitro diagnostic tests employ allergen extracts prepared from various allergen sources (e.g., pollen, mites, animal dander, moulds, foods, venoms, etc.). The application of recombinant DNA technology to the field of allergen characterization has allowed to reveal the molecular nature of the most common allergens. To date a continuously increasing number of allergen sequences has become available and panels of recombinant allergens-assembling the epitope complexity of natural allergens sources-can be produced. The use of recombinant allergens instead of crude, natural extracts for allergy diagnosis allows us to determine the individual IgE reactivity profile of each patient. To enable a comprehensive analysis of the patient's IgE binding pattern to a large number of individual allergens, a new type of serological test is required. In this paper, we applied microarray technology to create a multi-allergen test system, based on microarrayed recombinant allergens.

Allergens↗
PubMed2005

Peptide mass fingerprinting.

Peptide mass fingerprinting by MALDI-MS and sequencing by tandem mass spectrometry have evolved into the major methods for identification of proteins following separation by two-dimensional gel electrophoresis, SDS-PAGE or liquid chromatography. One main technological goal of proteome analyses beside high sensitivity and automation was the comprehensive analysis of proteins. Therefore, the protein species level with the essential information on co- and post-translational modifications must be achieved. The power of peptide mass fingerprinting for protein identification was described here, as exemplified by the identification of protein species with high molecular masses (spectrin alpha and beta), low molecular masses (elongation factor EF-TU fragments), splice variants (alpha A crystallin), aggregates with disulfide bridges (alkylhydroperoxide reductase), and phosphorylated proteins (heat shock protein 27). Helpful tools for these analyses were the use of the minimal protein identifier concept and the software program MS-Screener to remove mass peaks assignable to contaminants and neighbor spots.

Alternative Splicing↗
PubMed1998

Early assessment and in-hospital management of patients with acute myocardial infarction at increased risk for adverse outcomes: a nationwide perspective of current clinical practice. The National Registry of Myocardial Infarction (NRMI-2) Participants.

BACKGROUND: Therapeutic decision making in critically ill patients requires both prompt and comprehensive analysis of available information. Data derived from randomized clinical trials provide a powerful tool for risk assessment in the setting of acute myocardial infarction (MI); however, timely and appropriate use of existing therapies and resources are the key determinants of outcome among high-risk patients. METHODS: Demographic, procedural, and outcome data from patients with MI were collected at 1073 U.S. hospitals collaborating in the National Registry of MI (NRMI 2). Patients were classified on hospital arrival as either "low risk" or "high risk" according to a modified Thrombolysis in Myocardial Infarction II Risk Scale based on predetermined demographic, electrocardiographic, and clinical features. RESULTS: Among the 170,143 patients enrolled, 115,222 (67.5%) were classified as low risk and 55,521 (32.5%) as high risk for in-hospital death, recurrent ischemia, recurrent MI, congestive heart failure, and stroke. Using a composite unsatisfactory outcome measure, in-hospital adverse events were had by a greater proportion of patients initially classified as high risk compared with those classified as low risk. By multivariate analysis, age >70 years, prior MI, Killip class >1, anterior site of infarction, and the combination of hypotension and tachycardia were independent predictions of poor outcome in patients with or without ST-segment elevation on the presenting electrocardiogram. High-risk patients with ST-segment elevation were treated with thrombolytics (47.5%) or alternative forms of reperfusion therapy (9.3%) within 62 minutes and 226 minutes of hospital arrival, respectively. High-risk patients offered reperfusion therapy were also more likely to receive aspirin, beta-blockers (intravenous, oral) and angiotensin-converting enzyme inhibitors within 24 hours of infarction (all p < 0.0001), survive their event (8.4% versus 21.4% p < 0.0001), and leave the hospital sooner than those not reperfused. CONCLUSIONS: This large registry experience included more than 150,000 nonselected patients with MI and suggests that high-risk patients can be identified on initial hospital presentation. The current use of reperfusion and adjunctive therapies among high-risk patients is suboptimal and may directly influence outcome. Randomized trials designed to test the impact of specific management strategies on outcome according to initial risk classification are warranted.

Angioplasty, Balloon, Coronary↗
PubMed1999

Angiographic methods to assess human coronary angiogenesis.

It is unclear how agents designed to promote angiogenesis in the human heart affect the arteriographic appearance of the collateral circulation. Possible changes in collateral vessels include new collateral vessels arising from epicardial arteries, new branches emanating from existing collateral vessels, wider or longer collateral vessels, and higher dye transit rates that result in improved recipient vessel filling. Given the multiple mechanisms by which these new agents may improve myocardial perfusion, a rigorous, systematic, and comprehensive analysis of coronary arteriograms is required to discern the true mechanism of benefit. The method of analysis must account for potential changes in collateral blood flow, number, branching pattern, and length as well as changes in recipient vessel filling. The ability to detect differences between intricate networks of vessels in an angiographic study is dependent on maintaining consistency in cinefilming as well as the core laboratory methods between time points. In this report, we describe the methodology our angiographic core laboratory has found to be most effective to evaluate these very complex angiograms and attempt to capture all the possible modalities of angiogenesis.

Collateral Circulation↗
PubMed2001

Restenosis after coronary placement of various stent types.

Coronary stent implantation is being performed in an increasing number of patients with a wide spectrum of clinical and lesion characteristics. A variety of stent designs are now available and continuous efforts are being made to improve the stent placement procedure. The objective of this study was to perform a comprehensive analysis of the relation between clinical, lesion, and procedural factors, and restenosis after intracoronary stenting in a large and unselected population of patients. A consecutive series of 4,510 patients with coronary stent placement was analyzed. Exclusion criteria were only a failed procedure and an adverse outcome within the first month after the intervention. Follow-up angiography was performed in 80% of patients at 6 months. Clinical, lesion, and procedural data from all 3,370 patients (4,229 stented lesions) with follow-up angiography were analyzed in a logistic regression model for restenosis (> or =50% diameter stenosis). Clinical factors contributed to the predictive power of the model much less than lesion and procedural factors. The strongest risk factor for restenosis was a small vessel size, with a 79% increase in the risk for a vessel of 2.7 mm versus a vessel of 3.4 mm in diameter. Stent design was the second strongest factor; the incidence of restenosis ranged from 20.0% to 50.3% depending on the stent type implanted. In conclusion, this study demonstrates the predominant role of lesion and procedural factors in determining the occurrence of restenosis after coronary stent placement. Among these factors, stent design appears to play a particularly important role in the hyperplastic response of the vessel wall.

Analysis of Variance↗
PubMed1994

Vagaries of the lavage white blood cell count in evaluating abdominal stab wounds.

BACKGROUND: The clinical value of an elevated white blood cell (WBC) count on a diagnostic peritoneal lavage (DPL) performed in an asymptomatic patient with a penetrating abdominal stab wound is controversial. METHODS: We performed a comprehensive analysis of asymptomatic patients (no signs of peritonitis) with stab wounds who underwent an exploratory laparotomy based solely on a WBC count > 500/mm3 in the effluent of an open DPL. RESULTS: Twenty-eight patients, 25 with injury to the gastrointestinal (GI) tract and 3 with injury to the liver, obtained true-positive results from DPL. Their mean WBC count in lavage effluent obtained at a mean of 7.6 hours after the stab wound was 3,380/mm3 and their mean serum WBC count, obtained at the same time, was 12,324/mm3. Fifteen patients had false-positive results from DPL. They were lavaged at a mean of 7.2 hours after the stab wound, and had a mean lavage WBC count of 1,228/mm3 and a mean serum WBC count of 9,084/mm3. CONCLUSIONS: Patients lavaged at a mean 6 to 7 hours after an abdominal stab wound will have a significant incidence of false-positive studies based on an elevated WBC count alone. Lavage WBC counts > 3,000/mm3, particularly when associated with a serum WBC count > 11,000, are likely to be true positives and to indicate injury to the GI tract.

Abdominal Injuries↗