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This review summarizes the level of epidemiologic evidence for relationships between prenatal and/or early life exposure to environmental chemical contaminants and fetal, child, and adult health. Discussion focuses on fetal loss, ...
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This review summarizes the level of epidemiologic evidence for relationships between prenatal and/or early life exposure to environmental chemical contaminants and fetal, child, and adult health. Discussion focuses on fetal loss, intrauterine growth restriction, preterm birth, birth defects, respiratory and other childhood diseases, neuropsychological deficits, premature or delayed sexual maturation, and certain adult cancers linked to fetal or childhood exposures. Environmental exposures considered here include chemical toxicants in air, water, soil/house dust and foods (including human breast milk), and consumer products. Reports reviewed here included original epidemiologic studies (with at least basic descriptions of methods and results), literature reviews, expert group reports, meta-analyses, and pooled analyses. Levels of evidence for causal relationships were categorized as sufficient, limited, or inadequate according to predefined criteria. There was sufficient epidemiological evidence for causal relationships between several adverse pregnancy or child health outcomes and prenatal or childhood exposure to environmental chemical contaminants. These included prenatal high-level methylmercury (CH(3)Hg) exposure (delayed developmental milestones and cognitive, motor, auditory, and visual deficits), high-level prenatal exposure to polychlorinated biphenyls (PCBs), polychlorinated dibenzofurans (PCDFs), and related toxicants (neonatal tooth abnormalities, cognitive and motor deficits), maternal active smoking (delayed conception, preterm birth, fetal growth deficit [FGD] and sudden infant death syndrome [SIDS]) and prenatal environmental tobacco smoke (ETS) exposure (preterm birth), low-level childhood lead exposure (cognitive deficits and renal tubular damage), high-level childhood CH(3)Hg exposure (visual deficits), high-level childhood exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (chloracne), childhood ETS exposure (SIDS, new-onset asthma, increas...
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Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related mortality worldwide and 80%–90% of HCC develops in patients that have underlying cirrhosis. Better methods of surveillance are needed to increase ea...
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Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related mortality worldwide and 80%–90% of HCC develops in patients that have underlying cirrhosis. Better methods of surveillance are needed to increase early detection of HCC and the proportion of patients that can be offered curative therapies. Recent work in novel mass spec-based methods for glycomic and glycopeptide analysis for discovery and confirmation of markers for early detection of HCC versus cirrhosis is reviewed in this chapter. Results from recent work in these fields by several groups and the progress made in developing markers of early HCC which can outperform the current serum-based markers are described and discussed. Also, recent developments in isoform analysis of glycans and glycopeptides and in various mass spec fragmentation methods will be described and discussed. ? 2023
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To examine brain patterns of metabolic and functional activity, the distribution of cytochrome oxidase, a mitochondrial enzyme marker for neuronal functional activity, was mapped throughout the rat brain. Mapping was done qualitat...
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To examine brain patterns of metabolic and functional activity, the distribution of cytochrome oxidase, a mitochondrial enzyme marker for neuronal functional activity, was mapped throughout the rat brain. Mapping was done qualitatively by enzyme histochemistry of brain sections cut in three planes (coronal, sagittal and horizontal), and quantitatively by optical densitometry of stained sections and by biochemical assays of brain tissue homogenates. Activity of the enzyme was distributed in characteristic patterns and amounts that differed among various neural pathways, brain nuclei, cerebral cortical areas and layers, and neuron types. Gray matter essentially always had higher enzyme activity than did white matter, by a factor of eight- to 12-fold. Among different neural pathways, cytochrome oxidase activity was relatively high in special sensory, somatosensory and motor systems, and was relatively low in associative, limbic, autonomic and visceral regulatory systems (though exceptional areas were present). Among 11 different neuron types, nearly a two-fold range of histochemical staining intensities was observed, with the darkest staining in neurons of the mesencephalic trigeminal nucleus. The observed patterns of cytochrome oxidase activity were mostly similar to the patterns of 2-deoxyglucose uptake seen previously [Schwartz W. J. and Sharp F. R. (1978) J. comp. Neurol. 177, 335-360; Sokoloff L. et al. (1977) J. Neurochem. 28, 897-916] in conscious, "resting" animals, though some differences were found. For example, whereas 2-deoxyglucose uptake was about three-fold higher in gray matter than in white matter [Sokoloff L. et al. (1977) J. Neurochem. 28, 897-916], cytochrome oxidase activity was about eight- to 12-fold higher. This and other discrepancies probably reflect basic technical differences between these two methods. Compared to 2-deoxyglucose, cytochrome oxidase is more specific for oxidative rather than glycolytic metabolism, and more reflective of overall neuronal functional activity occurring over longer time periods lasting hours to weeks, rather than minutes. The anatomical resolution of cytochrome oxidase histochemistry is also finer than that of 2-deoxyglucose autoradiography, extending to the electron microscopic level. The metabolic map of cytochrome oxidase activity reveals patterns of normal brain function, and may be useful as a baseline for comparison in studies of brain disease, development, ageing and plasticity.
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The molecular clock machinery in mammals consists of a number of clock genes (CGs) and their resultant proteins that form interlocking tran scription-translation feedback loops. These loops generate and maintain the 24 h mRNA and ...
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The molecular clock machinery in mammals consists of a number of clock genes (CGs) and their resultant proteins that form interlocking tran scription-translation feedback loops. These loops generate and maintain the 24 h mRNA and protein oscillations and consequential biological and physiological rhythms. To understand whether peripheral oscillators share similarly-timed clock machinery, the temporal expression patterns of the seven recognized key CGs (mPer1, mPer2, mCry1, mCry2, mRev-erb alpha, mClock, and raBmall) were examined simultaneously in six peripheral tissues in mice every 4 It for 24 h in synchronized light-dark conditions using real time PCR assays. Time series were analyzed for time-effect by ANOVA and for rhythm characteristics by the single cosinor fitting procedure. The expression levels of most CGs were comparable in liver, kidney, and spleen, but mBmall and mCry1 were more abundant in the thymus, and mPerl, mCry1, and mCry2 were more abundant in the testis. In addition, mCry2 was dramatically lower in the kidney, spleen, and thymus; mPer2 was significantly lower in the spleen, testis, and thymus; and all of the genes tested were strikingly less abundant in peripheral blood. A significant 24 h rhythmic component was found for each CG in the liver and kidney and for some CGs in other tissues. Of note, a 12 h ultradian rhythmic component was also found in mRNA expression for some CGs in several of the tissues and was the only significant oscillation observed for CGs in the testis. Ultradian oscillations were also observed for mPer1 in the testis (8 h) and thymus (12 h and 8 h) in a second study where mice were sampled every 2 h. The present results suggest that the functioning of the molecular circadian clock may be modified to some extent between peripheral tissues, as denoted by differences in amplitude and phasing, and operates differently or is less developed in tissues
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Exact solutions are derived for an n-dimensional radial wave equation with a general power nonlinearity. The method, which is applicable more generally to other nonlinear PDEs, involves an ansatz technique to solve a first-order P...
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Exact solutions are derived for an n-dimensional radial wave equation with a general power nonlinearity. The method, which is applicable more generally to other nonlinear PDEs, involves an ansatz technique to solve a first-order PDE system of group-invariant variables given by group foliations of the wave equation, using the one-dimensional admitted point symmetry groups. (These groups comprise scalings and time translations, admitted for any nonlinearity power, in addition to space-time inversions admitted for a particular conformal nonlinearity power.) This is shown to yield not only group-invariant solutions as derived by standard symmetry reduction, but also other exact solutions of a more general form. In particular, solutions with interesting analytical behavior connected with blow-ups as well as static monopoles are obtained. (C) 2004 Elsevier Inc. All rights reserved.
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The completion of the human genome project, the evolution of transcriptional profiling and the emergence of proteomics have focused attention on these areas in the pathophysiology and therapy of cancer. The role of lysophospholipi...
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The completion of the human genome project, the evolution of transcriptional profiling and the emergence of proteomics have focused attention on these areas in the pathophysiology and therapy of cancer. The role of lysophospholipids as potential mediators in cancer pathophysiology, screening and management has taken a major leap forward with the recent cloning of several enzymes involved in the metabolism of lysophospholipids. Lysophospholipids, although small molecules, contain a high "informational" content. Differences include the nature of the phosphate head group, the regiochemistry of the fatty acyl chain on the glyceryl backbone, the presence of ether versus ester linkages to the backbone, and the length and saturation of the fatty acyl or alkyl chain. This informational content is sufficient to result in a marked structure function activity relationship at their cognate receptors. Thus the emerging discipline of "functional lipidomics" is likely to prove as important as genomics and proteomics in terms of early diagnosis, prognosis, and therapy. Lysophospholipid levels are elevated in vivo in a number of pathophysiological states including ascitic fluid from ovarian cancer patients indicating a role in the pathophysiology of this devastating disease. Although controversial, levels of specific lysophospholipids may be altered in the blood of cancer patients providing a potential mechanism for early diagnosis. Several of the enzymes involved in the metabolism of lysophospholipids are aberrant in ovarian and other cancers. Further, the enzymes are active in the interstitial space, rendering them readily accessible to the effects of inhibitors including antibodies, proteins, and small molecules. In support of a role for lysophospholipids in the pathophysiology of cancer, expression of receptors for lysophospholipids is also aberrant in cancer cells from multiple different lineages. All of the cell surface receptors for lysophospholipids belong to the G protein coupled receptor family. As over 40% of all drugs in current use target this family of receptors, lysophospholipid receptors are highly "druggable." Indeed, a number of highly specific agonists and antagonists of lysophospholipid receptors have been identified. A number are in preclinical evaluation as therapeutics. We look forward to the next several years when the role of lysophospholipids in physiology and the pathophysiology and management of cancer and other diseases are fully elucidated.
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The propensity of the transition of fracture type in either brittle or ductile cracked solid under mixed-mode I and III loading conditions is investigated. A fracture criterion based on the competition of the maximum normal stress...
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The propensity of the transition of fracture type in either brittle or ductile cracked solid under mixed-mode I and III loading conditions is investigated. A fracture criterion based on the competition of the maximum normal stress and maximum shear stress is utilized. The prediction of the fracture type is determined by comparing tau(max)/sigma(max) at a critical distance from the crack tip to the material strength ratio tau(C)/sigma(C), i.e., (tau(max)/sigma(max)) < (tau(C)/sigma(C)) for tensile fracture and (tau(max)/sigma(max)) > (tau(C)/sigma(C)) for shear fracture, where sigma(C) (tau(C)) is the fracture strength of materials in tension (shear). Mixed mode I/III fracture tests were performed using circumferentially notched cylindrical bars made of PMMA and 7050 aluminum alloy. Fracture surface morphology of the specimens reveals that: (1) for the brittle material, PMMA, only tensile type of fracture occurs, and (2) for the ductile material, 7050 aluminum alloy, either tensile or shear type of fracture occurs depending on the mode mixity. The transition (in ductile material) or non-transition (in brittle material) of the fracture type and the fracture path observed in experiments were properly predicted by the theory. Additional test data from open literature are also included to validate the proposed theory. (C) 2004 Elsevier Ltd. All rights reserved.
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Traditional Chinese medicines (TCMs) are getting more and more popular nowadays in the whole world for improving health condition of human beings as well as preventing and healing diseases. TCM is a multi-component system with com...
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Traditional Chinese medicines (TCMs) are getting more and more popular nowadays in the whole world for improving health condition of human beings as well as preventing and healing diseases. TCM is a multi-component system with components mostly unknown, and only a few compounds are responsible for the pharmaceutical and/or toxic effects. The large numbers of other components in the TCM make the screening and analysis of the bioactive components extremely difficult. So, separation and analysis of the desired chemical components in TCM are very important subjects for modernization research of TCM. Thus, many novel separation techniques with significant advantages over conventional methods were introduced and applied to separation and analysis of the chemical constituents in TCM. This review presents just a brief outline of the applications of different separation methods for the isolation and analysis of TCM constituents.
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Receptor-based radiopharmaceuticals are of great current interest in molecular imaging and radiotherapy of cancers, and provide a unique tool for target-specific delivery of radionuclides to the diseased tissues. In general, a tar...
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Receptor-based radiopharmaceuticals are of great current interest in molecular imaging and radiotherapy of cancers, and provide a unique tool for target-specific delivery of radionuclides to the diseased tissues. In general, a target-specific radiopharmaceutical can be divided into four parts: targeting biomolecule (BM), pharmacokinetic modifying (PKM) linker, bifunctional coupling or chelating agent (BFC), and radionuclide. The targeting biomolecule serves as a carrier modify radiotracer excretion kinetics. BFC is needed for radiolabeling of biomolecules with a metallic radionuclide. Different radiometals have significant difference in their coordination chemistry, and require BFCs with different donor atoms and chelator frameworks. Since the radiometal chelate can have a significant impact on physical and biological properties of the target-specific radiopharmaceutical, its excretion kinetics can be altered by modifying the coordination environment with various chelators or coligand, if needed. This review will focus on the design of BFCs and their coordination chemistry with technetium, copper, gallium, indium, yttrium and lanthanide radiometals.
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Mature pollen from most plant species is metabolically quiescent; however, after pollination, it germinates quickly and gives rise to a pollen tube to transport sperms into the embryo sac. Because methods for collecting a large am...
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Mature pollen from most plant species is metabolically quiescent; however, after pollination, it germinates quickly and gives rise to a pollen tube to transport sperms into the embryo sac. Because methods for collecting a large amount of in vitro germinated pollen grains for transcriptomics and proteomics studies from model plants of Arabidopsis and rice are not available, molecular information about the germination developmental process is lacking. Here we describe a method for obtaining a large quantity of in vitro germinating rice pollen for proteomics study. Two-dimensional electrophoresis of approximately 2300 protein spots revealed 186 that were differentially expressed in mature and germinated pollen. Most showed a changed level of expression, and only 66 appeared to be specific to developmental stages. Furthermore 160 differentially expressed protein spots were identified on mass spectrometry to match 120 diverse protein species. These proteins involve different cellular and metabolic processeswith obvious functional skew toward wall metabolism, protein synthesis and degradation, cytoskeleton dynamics, and carbohydrate/energy metabolism. Wall metabolism-related proteins are prominently featured in the differentially expressed proteins and the pollen proteome as compared with rice sporophytic proteomes. Our study also revealed multiple isoforms and differential expression patterns between isoforms of a protein. These results provide novel insights into pollen function specialization.
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