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Biomedical subjects

A R Price

Publications and source records attributed to A R Price.

At least 19 recordsLinked to original sources

The marine food chain in relation to biodiversity.

Biodiversity provides "raw materials" for the food chain and seafood production, and also influences the capacity of ecosystems to perform these and other services. Harvested marine seafood species now exceed 100 million t y(-1) and provide about 6% of all protein and 17% of animal protein consumed by humans. These resources include representatives from about nine biologically diverse groups of plants and animals. Fish account for most of the world"s marine catches, of which only 40 species are taken in abundance. Highest primary productivity and the richest fisheries are found within Exclusive Economic Zones (EEZ). This narrow strip (200 nautical mile/370 km wide) is not only the site of coastal "food factories" but also the area associated with heaviest perturbation to the marine environment. Structural redundancy is evident in marine ecosystems, in that many species are interchangeable in the way they characterise assemblage composition. While there is probably functional redundancy within groups, the effects of species loss on ecosystem performance cannot be easily predicted. In particular, the degree to which biodiversity per se is needed for ecosystem services, including seafood/fishery production, is poorly understood. Many human activities, including unsustainable fishing and mariculture, lead to erosion of marine biodiversity. This can undermine the biophysical cornerstones of fisheries and have other undesirable environmental side effects. Of direct concern are "species effects", in particular the removal of target and non-target fishery species, as well as conservationally important fauna. Equally disrupting but less immediate are "ecosystem effects", such as fishing down the food web, following a shift from harvested species of high to low trophic level. Physical and biological disturbances from trawl nets and dynamite fishing on coral reefs can also severely impact ecosystem structure and function. "Broadscale" biological and social effects brought about by fishing carry even more far-reaching consequences. For example, fishing itself can change the age at which sexual maturity is reached, thus affecting the reproductive status of the stock. Hence, fishing may be regarded as a mediator of evolution. Social impacts include conflicts over fish prices and policies arising from heavy fishing and inadequate institutional structures. Measures to increase the sustainability of catches and of biodiversity need to be much more tightly coupled. Promising approaches include use of bio-economic indicators and fully protected marine areas. High- and local-level governance options are also examined. Use of expert systems incorporating "fuzzy logic" are providing useful environmental insights in the ASEAN countries and other parts of the world, and have applications in fishery management and biodiversity conservation.

Animals↗

Chemorepellent signaling through the PACAP/lysozyme receptor is mediated through cAMP and PKC in Tetrahymena thermophila.

Pituitary adenylate cyclase-activating peptide and lysozyme are potent chemorepellents which act through the same receptor in Tetrahymena. Using in vivo behavioral studies, we have found that the pituitary adenylate cyclase-activating peptide/lysozyme receptor appears to signal through a G-protein pathway which is mediated through both adenosine 3'5'monophosphate and protein kinase C. Avoidance to pituitary adenylate cyclase-activating peptide and lysozyme is inhibited by the G-protein inhibitor, guanosine 5'-O-(2thiodiphosphate), the adenosine 3'5'monophate analog, Rp-adenosine-3', 5' cyclic monophosphorothioate, and the protein kinase C inhibitors, calphostin C and bisindolylmaleimide IV. A proposed model for signaling through the pituitary adenylate cyclase-activating peptide/lysozyme receptor is briefly outlined.

Animals↗

Anonymity and pseudonymity in whistleblowing to the U.S. Office of Research Integrity.

Given the concerns expressed by members of the academic and legal community about whether (and how) to handle anonymous and pseudonymous allegations of scientific misconduct, this paper summaries the experiences of the Office of Research Integrity and its predecessor from 1989 through 1997. Although the record shows that research institutions and the ORI have treated such allegations seriously, the fraction of complainants to the ORI who remain anonymous is small (8% of 986 allegations); few anonymous complaints are sufficiently substantive to be pursued (4% of the 357 formal cases opened in the ORI); and only 1 of these 13 cases resulted in an ORI finding of scientific misconduct.

Anonyms and Pseudonyms↗

A preliminary assessment of intra-oral lubricating systems for dry mouth patients.

OBJECTIVE: To provide extended intra-oral delivery of a saliva substitute. INTERVENTION: Three different types of prostheses containing saliva substitute were designed and assessed: a two-part device resembling a mandibular complete denture sealed by cobalt-samerium magnets, a one-part clear resin device for the edentate patients and a flexible mouth guard type of appliance containing a lubricant releasing bubble for the dentate patients. SETTING: A teaching hospital Oral Medicine and Rheumatology Clinic. SUBJECTS: 8 edentate and 3 dentate Sjogren Syndrome sufferers. OUTCOME MEASURES: Subjective dryness after a week of wearing the lubricating appliance. RESULTS: The majority of the subjects wore the appliances for 6-12 hours during each 24 hours. The initial dryness severity diminished after wearing the lubricating prosthesis. The patients preferred to wear the appliance at night. CONCLUSION: All criteria were fulfilled on designing a saliva substitute lubricating appliance and some of the subjects have worn this prosthesis successfully for up to 3 years. Particular benefit was obtained by night-time wear.

Aged↗

ORI defended.

Explore the source record for details and available documents.

Congresses as Topic↗

Problems in research integrity arising from misconceptions about the ownership of research.

Many allegations of scientific misconduct result from activities that are perceived by the complainants as the "theft" of ideas, experimental results, or other intellectual property. The authors' thesis is that many of these allegations originate in misconceptions about the ownership of publicly supported scientific research. Some universities and medical schools may have their own codes for authorship, and journals and professional societies have codes or guidelines. In the NIH intramural programs, research data are considered to be the property of the institutes, not the individual researchers. In contrast, the training and experience of most scientists lead them to consider research data as being theirs. The paper discusses the origins of this attitude toward data and the ways that the structures of university laboratories and training programs lead to confusion and misunderstandings of researchers' "rights" to data. Also, emotional and personality factors often complicate these issues and lead to confrontations. Other misconceptions widely held among researchers: the false concepts of "my grant" and the "co-principal" investigator, ideas about who is and is not qualified to be an author, and ideas about sharing data. The authors emphasize the importance of scientifically literate legal advisers and the necessity for graduate students, postdoctoral fellows, and professors to understand their institutions' and grantors' guidelines and their obligations as scientists. At the heart of these obligations at all levels of research is honesty.

Academic Medical Centers↗

Involvement of DNA repair in cancer and aging.

The theory of aging which proposes that DNA repair capacity declines with age and/or DNA damage accumulates with age, resulting in increasingly aberrant gene expression, is attractive but still unproven. Most results that do not support the theory are at least neutral. We propose that much of the ambiguity produced by work so far is due to (a) the difficulty of controlling all relevant variables, including particularly the proliferation state of the cells used and the location and nature of the damage being repaired, and (b) the existence of multiple and overlapping DNA repair pathways. A better knowledge of the critical, rate-limiting events in DNA repair in vivo, and the application of more sophisticated approaches for studying these events, may ultimately resolve the ambiguities. The causal relationship between DNA damage and cancer seems more secure. Declining DNA repair capacity with age would be expected to accelerate the increased incidence of cancer with age, but it is not known how important this is compared to other genetic and environmental variables. Results with genetic diseases generally support this view. Diseases characterized by DNA repair deficiencies are accompanied by phenomena that are also characteristic of normal aging, but a causal relationship has not been established. However, some of these diseases do constitute a strong risk factor for cancer. Even less convincing is a causal link between DNA repair deficiencies and aging in the so-called premature aging syndromes.

Aging↗

Septic erosion of the internal carotid artery. A case report.

A case of pseudo-aneurysm of the internal carotid artery with arterio-venous fistula formation, involvement of the vagus and sympathetic nerves and proptosis is described. The diagnostic features are stressed, namely: recurrent minor haemorrhages from the nose and throat, a Horner's Syndrome, a swelling resembling a quinsy and involvement of the last four cranial nerves. Early diagnosis and immediate ligation are essential in these cases.

Adult↗

Characterization of the Bacillus subtilis bacteriophage PBS2-induced DNA polymerase and its associated exonuclease activity.

The DNA polymerase induced by Bacillus subtilis bacteriophage PBS2 has a Stokes radius of 7.2 in buffers of high ioninc strength, suggesting a molecular weight in the range 145,000 to 195,000. The polypeptide bands observed on gel electrophoresis in dodecyl sulfate have apparent molecular weights of 78,000 and 69,000 (and possibly another 27,000) in equimolar amounts. In buffers of low ionic strength, the enzyme appears to form large aggregates and even precipitates, with about 90% loss of activity. A nuclease activity co-purifies with the PBS2 DNA polymerase and shows similar responses to changes in pH, MgCl2, N-ethylmaleimide, temperature, and dextran sulfate levels. The nuclease produces deoxyribonucleoside 5'monophosphates from denatured DNA containing thymine or uracil. No endonuclease activity is detectable on supercoiled DNA. The inhibition of nuclease activity by added deoxyribonucleoside triphosphates, the DNA-dependent turnover of triphosphates, to free monophosphates during DNA polymerization, the inhibition of nuclease activity by 3'-phosphates on the DNA template-primer, and the pattern of digestion of 5'-[32P]phosphate-labeled DNA all indicate that the PBS2 DNA polymerase-associated hydrolytic activity is a 3' leads to 5'-exonuclease.

Bacillus subtilis↗

Bacillus subtilis bacteriophage PBS2-induced DNA polymerase. Its purification and assay characteristics.

The DNA polymerase induced by Bacillus subtilis bacteriophage PBS2 (whose DNA contains uracil instead of thymine) has been purified and characterized for its specificity. The enzyme requires a high ionic strength for optimal stability and activity and is sensitive to various anions and to sulfhdryl reagents. Both dUTP and dTTP are incorporated efficiently as substrates and are competitive inhibitors at the same active site. The apparent Km and Ki values are about 6 micrometers for dTTP and 15 micrometers for dUTP, when denatured, uracil-containing B. subtilis or salmon sperm DNA (3.9 micrometers for dUTP and 2.6 micrometers for dTTP). The PBS2 enzyme works best on denatured DNA, on double-stranded DNA activated by DNase to produce gaps, or on primed homopolymeric DNA. Using denatured DNA preparations of average molecular weight 6.2 million, the apparent Km values are 270 micrograms/ml for B. subtilis DNA and 360 micrograms/ml for PBS2 DNA; the Vmax value for denatured PBS2 DNA containing uracil is 7-fold greater than that for denatured B. subtilis DNA containing thymine. However, lower molecular weight DNAs have 10-fold lower apparent Km values and show similar Vmax values for both B. subtilis and PBS2 DNAs. Thus, the PBS2 phage-induced DNA polymerase (which likely replicates only uracil-containing phage DNA using dUTP in vivo) has little selectivity for uracil- versus thymine-containing deoxyribonucleotides or DNA in vitro.

Bacillus subtilis↗

Two thymidylate synthetases in Bacillus subtilis.

Bacillus subtilis grown at temperatures below 37 degrees contains two thymidylate synthetases, TSaseA and TSaseB. Their presence is dependent on functional thyA and thyB genes, respectively. When cells are grown at 46 degrees they only contain TSaseA activity. This allous an easy positive selection for thyA and thyA, THYB mutants. The two TSases have been physically separated, and they show similar overall requirements for activity. However, they differ significantly in both their kinetic and their physicochemical properties.

Bacillus subtilis↗

Dextran sulfates as a contaminant of DNA extracted from concentrated viruses and as an inhibitor of DNA polymerases.

Dextran sulfate is commonly used with polyethylene glycol to concentrate viruses before extraction of their DNA. However, dextran slulfate then easily contaminated such DNA and acted as a potent inhibitor of DNA polymerases from Bacillus subtilis (III), phage PBS2, and phage T4. Dextran sulfate only weakly inhibited Micrococcus luteus and Escherichia coli DNA polymerase I preparations.

Bacteriophages↗

Relationship of Bacillus subtilis DNA polymerase III to bacteriophage PBS2-induced DNA polymerase and to the replication of uracil-containing DNA.

In vivo studies of PBS2 phage replication in a temperature-sensitive Bacillus subtilis DNA polymerase III (Pol III) mutant and a temperature-resistant revertant of this mutant have suggested the possible involvement of Pol III in PBS2 DNA synthesis. Previous results with 6-(p-hydroxyphenylazo)-uracil (HPUra), a specific inhibitor of Pol III and DNA replication in uninfected cells, suggest that Pol III is not involved in phage DNA replication, due to its resistance to this drug. Experiments were designed to examine possible explanations for this apparent contradiction. First, assays of the host Pol III and the phage-induced DNA polymerase activities in extracts indicated that a labile Pol III did not result in a labile phage-induced enzyme, suggesting that this new polymerase is not a modified HPUra-resistant form of Pol III. Indeed the purified phage-induced enzyme was resistant to the active, reduced form of HPUra under all assay conditions tested. Since in vitro Pol III was capable of replicating the uracil-containing DNA found in this phage, the sensitivity of the purified enzyme to reduced HPUra was examined using phage DNA as template-primer and dUTP as substrate; these new substrates did not affect the sensitivity of the host enzyme to the drug.

Bacillus cereus↗