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PubMed1978

Nutritional considerations in designing animal models of metal toxicity in man.

In recent years, exposure of man to increasing amounts of metals has occurred rather generally from industrial contamination and variably from intake of dietary mineral supplements. Adverse effects of individual metals can be markedly altered by dietary levels of other essential and nonessential inorganic elements, essential organic nutrients and other nonessential dietary components. Experimental diets for establishing baseline responses to excess elements should be formulated to meet the animal's requirements only. These reference diets can then be modified to mimic man's average dietary intake as well as meal patterns. Improved animal models should provide better data for assessing hazards of excess metal intake by man.

Aging↗

PubMed1998

An evolutionary conserved element is essential for somite and adjacent mesenchymal expression of the Hoxa1 gene.

The murine Hoxa1 gene is a member of the vertebrate Hox complex and plays a role in defining the body plan during development. At day 8.0-9.0 post coitus, Hoxa1 transcripts are detected extensively throughout the embryo in the neural tube, adjacent mesenchyme, paraxial mesoderm, somites and gut epithelium; expression extends from the most caudal region of the embryo to the rhombomere 3/4 border. This spatiotemporal expression of Hoxa1 mRNA is critical for normal embryonic development. We have previously identified a 10 bp element, called CE2, which is located approximately 3 kilobases 3' of the Hoxa1 coding region in the RAIDR5 enhancer, and which binds to an approximately 170 kd protein in retinoic acid treated P19 embryonal carcinoma cells. CE2 elements were also identified 3' of the murine Hoxb1 gene, the chicken Hoxb1 gene and the human Hoxa1 gene. To examine the role of this CE2 element in regulating Hoxa1 expression in vivo, transgenic mice were generated which express a Hoxa1 beta-galactosidase reporter gene that contains a mutation in the CE2 element. Relative to transgenic mice bearing a wild type CE2 element, the mutant CE2 construct recapitulated rhombomeric, neural, and gut epithelium expression but failed to show beta-galactosidase expression in somites and adjacent mesenchymal tissue. Gel shift analysis showed that binding activity similar to that detected in extracts prepared from retinoic acid treated P19 cells was present in nuclear extracts prepared from day 9.0 embryos. However, an additional binding complex not detected in P19 cells was also observed. These results indicate that in transgenic animals, the evolutionary conserved CE2 element is a somite and adjacent mesenchymal enhancer of Hoxa1 expression.

Animals↗

PubMed2005

Molecular and ionic mimicry and the transport of toxic metals.

Despite many scientific advances, human exposure to, and intoxication by, toxic metal species continues to occur. Surprisingly, little is understood about the mechanisms by which certain metals and metal-containing species gain entry into target cells. Since there do not appear to be transporters designed specifically for the entry of most toxic metal species into mammalian cells, it has been postulated that some of these metals gain entry into target cells, through the mechanisms of ionic and/or molecular mimicry, at the site of transporters of essential elements and/or molecules. The primary purpose of this review is to discuss the transport of selective toxic metals in target organs and provide evidence supporting a role of ionic and/or molecular mimicry. In the context of this review, molecular mimicry refers to the ability of a metal ion to bond to an endogenous organic molecule to form an organic metal species that acts as a functional or structural mimic of essential molecules at the sites of transporters of those molecules. Ionic mimicry refers to the ability of a cationic form of a toxic metal to mimic an essential element or cationic species of an element at the site of a transporter of that element. Molecular and ionic mimics can also be sub-classified as structural or functional mimics. This review will present the established and putative roles of molecular and ionic mimicry in the transport of mercury, cadmium, lead, arsenic, selenium, and selected oxyanions in target organs and tissues.

Animals↗

PubMed2003

Effect of bioaccumulation of cadmium on biomass productivity, essential trace elements, chlorophyll biosynthesis, and macromolecules of wheat seedlings.

Soil contamination with heavy metals has become a worldwide problem, leading to losses in agricultural yield and hazardous human health effects as they enter the food chain. The present investigation was undertaken to examine the influence of cadmium (Cd2+) on the wheat (Triticum aestivum L.) plant. Cd2+ accumulation and distribution in 3-wk-old seedlings grown in nutrient medium containing varying concentrations of Cd2+ (control, 0.25, 0.50, 1.0, 2.5, and 5.0 mg/L) was monitored. The effect of varying Cd2+ concentrations up to 21 d on biomass productivity, plant growth, photosynthetic pigments, protein, amino acids, starch, soluble sugars, and essential nutrients uptake was studied in detail to explore the level up to which the plant can withstand the stress of heavy metal. Plants treated with 0.5, 1.0, 2.5, and 5.0 mg/L Cd2+ showed symptoms of heavy-metal toxicity as observed by various morphological parameters which were recorded with the growth of plants. The root, shoot-leaf length and the root, shoot-leaf biomass progressively decreased with increasing Cd2+ concentration in the nutrient medium. Cd2+ uptake and accumulation was found to be maximum during the initial growth period. Cd2+ also interfered with the nutrients uptake, especially calcium (Ca2+), magnesium (Mg2+), potassium (K+), iron (Fe2+), zinc (Zn2+), and manganese (Mn2+) from the growth medium. Growth reduction and altered levels of major biochemical constituents such as chlorophyll, protein, free amino acids, starch, and soluble sugars that play a major role in plant metabolism were observed in response to varying concentrations of Cd2+ in the nutrient medium. In the present study, the effects of Cd2+ on growth, biomass productivity, mineral nutrients, chlorophyll biosynthesis, protein, free amino acid, starch, and soluble sugars in wheat plants was estimated to establish an overall picture of the Cd2+ toxicity at structural and functional levels.

Amino Acids↗

PubMed1996

9-Dihydroxy-2,3,7,11b-tetrahydro-1H-naph[1,2,3-de]isoquinoline: a potent full dopamine D1 agonist containing a rigid-beta-phenyldopamine pharmacophore.

The present work reports the synthesis and preliminary pharmacological characterization of 8,9-dihydroxy-2,3,7,11b-tetrahydro-1H-naph[1,2,3-de] isoquinoline (4, dinapsoline). This molecule was designed to conserve the essential elements contained in our D1 agonist pharmacophore model (i.e., position and orientation of the nitrogen, hydroxyls, and phenyl rings). It involved taking the backbone of dihydrexidine [3; (+/-)-trans-10, 11-dihydroxy-5,6,6a,7,8,12b-hexahydrobenzo[a] phenanthridine], the first high-affinity full D1 agonist, and tethering the two phenyl rings of dihydrexidine through a methylene bridge and removing the C(7)-C(8) ethano bridge. Preliminary molecular modeling studies demonstrated that these modifications conserved the essential elements of the hypothesized pharmacopore. Dinapsoline 4 had almost identical affinity (KI = 5.9 nM) to 3 at rat striatal D1 receptors and had a shallow competition curve (nH = 0.66) that suggested agonist properties. Consistent with this, in both rat striatum and C-6-mD1 cells, dinapsoline 4 was a full agonist with an EC50 of ca. 30 nM in stimulating synthesis of cAMP via D1 receptors. The design and synthesis of dinapsoline 4 provide a powerful test of the model of the D1 pharmacophore we have developed and provide another chemical series that can be useful probes for the study of D1 receptors. An interesting property of 3 is that it also has relatively high D2 affinity (K0.5 = 50 nM) despite having an accessory phenyl ring usually though to convey D1 selectivity. Dinapsoline 4 was found to have even higher affinity for the D2 receptor (K0.5 = 31 nM) than 3. Because of the high affinity of 4 for D2 receptors, it and its analogs can be powerful tools for exploring the mechanisms of "functional selectivity" (i.e., that 3 is an agonist at some D2 receptors, but an antagonist at others). Together, these data suggest that 4 and its derivatives may be powerful tools in the study of dopamine receptor function and also have potential clinical utility in Parkinson's disease and other conditions where perturbation of dopamine receptors is useful.

Adenylyl Cyclases↗

PubMed2003

Distribution of trace elements in the tissues of benthic and pelagic fish from the Kerguelen Islands.

New information on the concentrations of Cd, Cu, Hg and Zn in the liver, kidney and muscles of eight marine benthic and pelagic sub-Antarctic fish species are presented to determine the importance of these metals in the marine systems of the Kerguelen Islands. Compared to the reported metal concentrations in other Antarctic fish species, the present results are globally within the same range of concentrations, although Cd displayed a very high interspecific variability in liver and kidney. Indeed, the highest Cd concentrations in liver, ranging from 10.0 to 52.1 microg x g(-1) dry wt. but also the lowest Cd concentrations in muscles (<0.030 microg x g(-1) dry wt.) have been displayed by the pelagic Myctophidae Gymnoscopelus piabilis. Metal concentrations differences might be related to diet and feeding habits of benthic and pelagic fish species. However, Cd and Hg concentrations in the edible muscle are lower than the French limit values (<or=0.155 microg x Cd x g(-1) dry wt. and <or=1.51 microg x Hg x g(-1) dry wt.) for these toxic metals as well as for edible and non-commercially interesting fish species. Results for Cd in fish tissues are consistent with the hypothesis of Cd-enrichment in the polar food webs typically explained by essential elements depletion. In fact, Zn concentrations in fish from the Kerguelen Islands are comparable to those of other areas but low Cu concentrations in fish livers, ranging from 0.9 to 24.7 microg x g(-1) dry wt., might indicate low availability of this essential element in these sub-Antarctic waters.

Animals↗

PubMed2006

Lessons learned from pilot site implementation of an ambulatory electronic health record.

As ambulatory care practices face increasing pressure to implement electronic health records (EHRs), there is a growing need to determine the essential elements of a successful implementation strategy. HealthTexas Provider Network is in the process of implementing an EHR system comprising GE Centricity Physician Office-EMR 2005, Clinical Content Consultants (now part of GE), and Kryptiq Secure Messaging throughout all 88 practices in the Dallas-Fort Worth area and is hoping to extend the system to other practices affiliated with Baylor Health Care System as well. We describe the preimplementation clinical process redesign and quality improvement training that has been conducted networkwide in preparation for the introduction of the EHR, as well as the specific steps taken to prepare and train clinic staff for the integration of the EHR into daily workflows. The first pilot site, Family Medical Center at North Garland, implemented the system in May 2006. Based on both the positive aspects of this experience and the challenges we encountered, we identified 20 essential elements for successful implementation in the areas of site selection, implementation strategy, staff education and preparation, team project management, content, hardware and software, and workflow process. Broadly, we determined that 1) a pilot site's understanding of and willingness to work within the fluid nature of the implementation process during what is essentially a testing phase is a key ingredient in achieving success at the pilot site and in improving the process for later sites; 2) input from and representation of viewpoints of all types of EHR users during preimplementation decision making enables customization of the system and sufficient preplanning to ensure minimal workflow disruptions during and after implementation; and 3) a high level of technical and training support during the early days of implementation is invaluable.

Journal Article↗

PubMed1998

A steroidogenic factor-1 binding element is essential for basal human ACTH receptor gene transcription.

We have previously shown that the promoter of the human ACTH receptor (ACTH-R) contains, at -35 bp, a binding site for the steroidogenic factor 1 (SF-1), an orphan nuclear receptor which could be responsible for the transcriptional activity of this promoter. In the present study, electrophoretic mobility shift assays demonstrated that the sequence -43/-19 bound the SF-1 protein present in the nuclear extracts of adrenocortical cells. Mutation of the SF-1 binding site markedly reduced (40%) the basal transcription of the reporter gene in Y-1 cells transfected with the mutated p(-56/+22)GH construct compared to the wild-type construct. These results demonstrate that the SF-1 binding element present in this fragment is required for the basal promoter activity of the human ACTH-R gene. In addition, other binding elements located upstream from this characterized SF-1 binding site are involved in the full basal promoter activity of the human ACTH-R since transfection studies with a longer p(-1017/+22)GH construct resulted in a higher GH release than with the p(-56/+22)GH construct.

Animals↗

PubMed2006

Proximal cyclic AMP response element is essential for exendin-4 induction of rat EGR-1 gene.

Glucagon-like peptide-1 and its potent agonist exendin-4 induce several immediate early response genes (IEGs) that code for transcription factors implicated in cell proliferation, differentiation, and apoptosis. We recently observed that early growth response factor-1 (EGR-1), an IEG product, was required for transcriptional activation of Ccnd1 (cyclin D1) gene by exendin-4. Herein, the regulatory mechanism whereby exendin-4 activates the transcription of EGR-1 gene was investigated in the pancreatic beta-cell line INS-1. Deletion analysis of rat EGR-1 promoter identified a critical region between -73 and -46 for the activation of EGR-1 in response to exendin-4. Mutation of the proximal putative cAMP response element (CRE, 5'-GTACGTCA-3') located at -69 resulted in a significant decrease in the EGR-1 transcription, whereas the mutation of the distal putative CRE at -139 was without such an effect. In immune supershift assays using exendin-4-treated cells, binding of cAMP response element-binding protein (CREB) phosphorylated on Ser(133) to the proximal CRE was increased. Employment of a CREB mutant containing Ala substitution at Ser(133) or a dominant negative CREB mutant that inhibits the binding of endogenous CREB to DNA significantly decreased the exendin-4-induced EGR-1 transcription. In experiments using specific protein kinase inhibitors, the effect of H-89 was more prominent than PD-98059, indicating the predominance of the PKA signaling over the MEK/ERK in induction of EGR-1. Therefore, it appears that the proximal CRE site is critical and the binding with CREB phosphorylated on Ser(133) is necessary for induction of the EGR-1 transcription by exendin-4.

Animals↗

PubMed1993

Essential trace elements in humans. Serum arsenic concentrations in hemodialysis patients in comparison to healthy controls.

Serum arsenic concentrations of persons suffering from renal failure and undergoing hemodialysis treatment (n = 85) and of healthy controls (n = 25) were determined by hydride-generation AAS technique after microwave digestion. The results were evaluated by comparing the values of both groups, considering physiological factors and individual data, as well as comorbid conditions of the hemodialysis (HD) patients. Serum arsenic levels were diminished in the patient group compared with controls (mean values 8.5 +/- 1.8 ng/mL vs 10.6 +/- 1.3 ng/mL). Furthermore, additional diseases within the hemodialysis group, particularly injuries of the central nervous system (CNS), vascular diseases, and cancer, were correlated to occasionally markedly decreased serum arsenic concentrations. It was concluded that arsenic homeostasis is disturbed by HD treatment and certain additional diseases. Desirable arsenic concentrations in the body seem to be reasonable. This consideration results in the conclusion that arsenic could play an essential role in human health. Thus, reference arsenic concentrations in different human tissues and body fluids should be established in order to recognize not only arsenic intoxication, but also arsenic deficiency. Perhaps arsenic deficiency contributes to the increased death risk of HD patients, and therefore, arsenic supplementations for patients with extremely low serum arsenic concentrations should be taken into account.

Arsenic↗

PubMed1996

Core promoter elements are essential as selective determinants for function of the yeast transcription factor GAL11.

The GAL11 gene product, which copurifies with RNA polymerase II holoenzyme, is necessary for full expression of many, but not all, genes in yeast. Here we shows that the GAL11 dependence of a gene for expression is determined by the core promoter structure. In the GAL80 gene, a gal11 null mutation caused reduction of TATA-dependent transcription, but exerted no effect on initiator-mediated transcription. GAL11 stimulated TATA-dependent transcription, but did not affect the TATA-independent transcription in HIS4. GAL11 was also required for transcription mediated by a canonical TATA sequence but not by a nonconsensus TATA sequence of HIS3. These results suggest that GAL11 is specifically involved in the transcription machinery formed on the TATA element.

Fungal Proteins↗

PubMed1997

Partial characterization of the MPM-2 phosphoepitope.

The MPM-2 monoclonal antibody recognizes a distinctive group of proteins that are associated with structural components of the mitotic apparatus. These proteins become phosphorylated and MPM-2 reactive during M-phase and appear to be required for both the onset and completion of M-phase. Based upon the analysis of reported MPM-2 reactive sequences, we have developed a model for the essential elements that comprise the MPM-2 epitope. This model was tested by employing a series of synthetic phosphopeptides. We show here that a 14 amino acid synthetic phosphopeptide, derived from a potential MPM-2 site on human DNA topoisomerase II, is recognized by the MPM-2 antibody. This phosphopeptide was sufficient to compete for MPM-2 antibody recognition of (1) an isolated native mitotic MPM-2 antigen on dot blots, (2) proteins on immunoblots of mitotic cell lysates, and (3) specific immunostaining of mitotic cells. These results indicated that the topoisomerase peptide contained all of the essential elements of the MPM-2 epitope. By substituting selected amino acids with alanine, we were able to examine the contribution of different amino acids to the binding between the MPM-2 antibody and the epitope. Changing the amino acid that was adjacent to the phosphorylated threonine residue on the C-terminal side (the +1 position) had no effect on MPM-2 antibody binding. However, substitution of aromatic amino acids at either the -2 or +2 positions reduced antibody recognition. The aromatic amino acid at the -2 position appeared to be the most critical residue of those tested that influenced antibody binding. These results provide information required for the molecular definition of the MPM-2 epitope and should aid in the identification of potential MPM-2 reactive sites on other mitotic phosphoproteins.

Amino Acid Sequence↗

PubMed1997

A GT box element is essential for basal and cyclic adenosine 3',5'-monophosphate regulation of the human surfactant protein A2 gene in alveolar type II cells: evidence for the binding of lung nuclear factors distinct from Sp1.

The gene encoding surfactant protein-A (SP-A) is developmentally regulated in type II cells of the fetal lung. In humans there are two SP-A genes, SP-A1 and SP-A2. The SP-A2 gene is more highly regulated by cAMP and during fetal development than SP-A1. In earlier studies we determined that 296 bp of sequence flanking the 5'-end of the SP-A2 gene is sufficient to mediate high basal and cAMP-inducible reporter gene expression in primary cultures of transfected type II cells, suggesting that this region contains important cis-acting elements involved in tissue-specific and hormonal regulation of SP-A2 promoter activity. We also observed that mutagenesis of a cAMP response element (CRE)-like sequence at -242 bp (CRE(SP-A2)) greatly reduced basal and cAMP-stimulated expression in transfected type II cells. In the present study, we identified a GT box (GGGGTGGGG) at -61 bp of SP-A2 5'-flanking sequence that is highly conserved among the SP-A genes of different species. In type II cell transfection studies, we found that mutagenesis of the GT box of SP-A2 markedly reduced basal and abolished cAMP-induced reporter gene expression. Thus, CRE(SP-A2) and the GT box cooperatively interact to mediate basal and cAMP induction of SP-A2 promoter activity in type II cells. By electrophoretic mobility shift assays (EMSA), it was observed that nuclear proteins isolated from primary cultures of type II cells bound the GT box as five specific complexes. By contrast, nuclear proteins isolated from lung fibroblasts displayed notably reduced binding activity. Competition and supershift EMSA indicate that the ubiquitously expressed transcription factor Sp1, a GC box-binding protein of approximately 100 kDa, is a component of the complex of proteins that bind the GT box of SP-A2. The finding that only two of the five GT box-binding complexes were supershifted by incubation with Sp1 antibody suggests that a factor(s) in type II cell nuclear extracts that is distinct from Sp1 also interacts with the GT box. By UV cross-linking and SDS-PAGE/EMSA analysis, we have identified a approximately 55-kDa GT box-binding factor in type II cell nuclear proteins that preferentially binds the GT box of SP-A2 over the consensus Sp1 GC box sequence. This 55-kDa factor was able to bind the GT box independently of Sp1.

Animals↗

PubMed1999

An A/T-rich cis-element is essential for rat angiotensin II type 1A receptor transcription in vascular smooth muscle cells.

Transcriptional mechanisms regulating the expression of the rat angiotensin II type 1A receptor (rAT1AR) gene were investigated in cultured rat vascular smooth muscle cells (VSMC). Transcriptional analyses of various 5'-deletion mutants of the rAT1AR promoter region, fused upstream from the firefly luciferase gene, demonstrated that a 71 base pair (bp) region (-557 to -486 bp, with respect to transcription initiation) was necessary for expression of this gene in VSMC. Electrophoretic mobility shift assays demonstrated that specific protein-DNA complexes were formed with the -516 to -486 bp region of the rAT1AR promoter when incubated with VSMC extract. Computer analysis of this region indicated the presence of an A/T-rich sequence (i.e., TTTAAAAATAAA) which is similar to a myocyte enhancer binding factor 2 (MEF2) cis-regulatory element (i.e., CTTAAAAATAAC). Site-directed mutagenesis of this A/T-rich sequence inhibited rAT1AR promoter activity in VSMC, suggesting that this region was necessary for expression of this gene in these cells. Immuno-gel shift experiments suggest that MEF2 heterodimers may interact with the A/T-rich sequence in the rAT1AR promoter. Additionally, it was demonstrated that a transcription factor non-homologous to MEF2 can also interact with this A/T-rich site in the rAT1AR promoter. Taken together, our results suggest that MEF2 heterodimers, and/or transcription factors non-homologous to MEF2, are required to regulate the expression of the rAT1AR gene in VSMC.

Animals↗

PubMed2005

Using the worldwide web to improve children's pain care.

AIM: This paper describes a three-year project, the aims of which were to disseminate information regarding the assessment and management of children's pain, to reach consensus on the essential elements of pain assessment for children and to track nurses' perceived changes in pain assessment and management practices in hospital settings over time. BACKGROUND: Despite the availability of research, guidelines and standards, paediatric nurses inconsistently practice evidence-based pain management. PROJECT METHODS: Nurses attending the 5th International Symposium on Paediatric Pain were invited to a workshop to discuss best practices and consider ways to share information regarding the assessment and management of children's pain. A website was designed and participants provided hospital guidelines, exchanged information via the Internet and completed periodic surveys. CONCLUSION: Web-based resources were positively received. Consensus regarding the essential elements of pain management was achieved, but nurses identified organizational and resource restraints as barriers to achieving best practices. Surveys identified perceived increases in some hospital and ward level resources and activities to improve children's pain care. Sharing of information related to children's pain management and benchmarking of practice should be encouraged. Consensus building and networking may facilitate change, but organizational commitment is also required for successful implementation of new practices.

Consensus↗

PubMedDate not supplied

Selecting and implementing support groups for bereaved adults.

PURPOSE: This paper offers a rationale for initiating bereavement support groups in sites providing cancer care and delineates models to implement them. Skills needed to lead a bereavement support group are identified, with emphasis on adding to staff members' competency that has already been developed by facilitating groups for oncology patients and their families. OVERVIEW: Bereavement support groups are essential elements in the provision of comprehensive oncology care, though they are seldom offered by staff in the traditional hospital setting. It is important that the bereaved feel that there is a place in which they have the time and understanding required to work through the normal grieving process. Special requirements for facilitators include self-awareness of the impact of loss in their own lives and ability to tolerate both the emotions expressed in the grieving process and the often extended time period required for members' personal healing. Several bereavement support models, including the time-limited, ongoing, monthly, and self-help groups, are documented. CLINICAL IMPLICATIONS: Bereavement support is an essential element in the provision of comprehensive oncology care. Predictive models to identify individuals who are at higher risk for psychological distress could be used in oncology clinics to facilitate early referral or greater psychological support for family members. Staff members wishing to introduce this service can build on skills already developed leading traditional oncology support groups, and can utilize cofacilitation with a mental health professional to ease the anxiety of assuming a new role and obtain mentoring. Recruitment for a group might be achieved by inviting family members of patients who have died within a specific time frame or by issuing press releases to local papers and church bulletins. Offering bereavement support in the oncology setting is especially helpful to family members who might otherwise be unaware of such a service and who now have the opportunity to attend.

Adult↗

PubMed1996

A novel cis-acting element is essential for cytokine-mediated transcriptional induction of the serum amyloid A gene in nonhepatic cells.

Serum amyloid A (SAA) is a plasma protein which has been associated with several diseases, including amyloidosis, arthritis, and atherosclerosis, and its abnormal expression, particularly in nonhepatic cells, is implicated in the pathogenesis of these diseases. Transfection and DNA-binding studies were performed to investigate the mechanism controlling cytokine-induced, nonhepatic expression of the SAA gene. We have identified a novel promoter, located between positions -280 and 224, that confers interleukin-6 (IL-6) inducibility to an SAA-chloramphenicol acetyltransferase reporter gene in both nonhepatic and hepatic cells. DNase I protection assays revealed, within this region, three homologous highly pyrimidine rich octanucleotide sequence motifs, termed SAA-activating sequences (SAS). Specific mutations within these three SAS motifs severely reduced IL-6-mediated induction of the reporter gene in transfected nonhepatic cells but not in liver cells. A nuclear factor activated by IL-6 in both hepatic and nonhepatic cells efficiently interacts with the SAS. The induction kinetics and cycloheximide sensitivity of this SAS-binding factor (SAF) suggested that de novo synthesis of this factor itself or an activator protein is essential. Loss of DNA-binding ability as a result of in vitro dephosphorylation, induction of SAA-chloramphenicol acetyltransferase reporter gene activity in the presence of genistein, a protein kinase inhibitor, further indicate that a phosphorylation step is necessary for the activation of SAF. Our results suggest that SAF is a key regulator of cytokine-mediated SAA gene expression in some nonhepatic cells.

Animals↗

PubMedDate not supplied

[Historical necessity and human action in Morte e vida severina].

Using the essential elements of tragic action described in Aristotles Poetics, the text compares João Cabral de Melo Neto's Morte e vida severina to Sophocles Oedipus rex with the purpose of bringing to light the tension that exists between human necessity and human action. It is an eminently epidemiological fact that draws a link between these two works. In Morte e vida severina, the causa efficiens behind Severino's decision to migrate is a famine; in Oedipus rex, a plague afflicting the inhabitants of Thebes is the event that hastens discovery of king Laiuss true assassin. It is a reflection on the finalis and formalis causes behind Severino's and Oedipus's movements and on the essential elements of tragic action that allows a transitory falsification or, better put, a rejection of the hypothesis that Morte e vida severina is a tragedy, at least not in Aristotelian terms.

Brazil↗