ALTERNATIVES TO THE USE OF ANTIBIOTICS AS GROWTH PROMOTERS FOR MONOGASTRIC ANIMALS

ABSTRACT

Recently, more and more is becoming known about the mode of action of antibiotics as growth promoters (AMGP), particularly in relation to the development of microbial resistance. Consequently, the use of these AMGP is already restricted or forbidden in many countries. Therefore, to compensate for the possible decrease in production, a lot of work is now being done to investigate possible alternatives. Suitable alternatives must be both proven and cost-effective, for the conditions and diets as used at the farm level.     

Testing alternative vicariance scenarios in Western Mediterranean discoglossid frogs

Dated molecular phylogenies are often used to interpret evolutionary history with respect to paleogeographic events. Where more than one interpretation is possible, it is desirable but difficult to assess the alternatives in an objective manner. The present work demonstrates a formalized method for testing molecular clock calibrations and biogeographic scenarios based on them. We assessed the plausibility of several previously published biogeographic hypotheses, using the frog genera Alytes, Discoglossus, and Bombina as model groups. Our data set comprised ca. 900bp of partial mitochondrial 16S and 12S rRNA gene sequences (both genes evolved in a clock-like manner across genera) from nearly all the species and subspecies in the three genera. We tested several calibrations of a molecular clock, which resulted in competing temporal settings for the evolution of taxa. Although only one scenario was in complete accordance with paleogeographic data, statistical testing did not reject the alternatives. Limitations encountered with the present approach may be overcome by more comprehensive analyses in future.     

Isochromosome not translocation in trisomy 21q21q

Summary After primary trisomy, de novo 21q21q trisomy is the most frequent chromosomal aberration responsible for Down syndrome. This rearrangement is more commonly referred to as a Robertsonian translocation or centric fusion product than as an isochromosome, e.g., t(21q;21q) instead of i(21q); however, in practice, it has not so far proved possible to distinguish between these alternatives. The aim of this work was to establish which of the two alternatives is acceptable.     

Nomenclature of precancerous lesions of the uterine cervix. A position paper

There is universal and almost unanimous belief that there is a need for a radical revision of the terminology relating to the epithelial abnormalities of the uterine cervix that precede invasive carcinoma. Although this belief has been held for some years, no generally accepted alternative system has, as yet, been devised. This position paper examines (1) the origin of the existing system of terminology, (2) the problems associated with this system and (3) the requirements of any new, alternative nomenclature. The various alternatives that have been suggested are considered with particular reference to their advantages and disadvantages. Only two such alternatives are considered to be acceptable, and it is suggested that neither is likely to gain universal acceptance at this time. However, it is possible that new diagnostic techniques, with their potential for a more accurate evaluation of cell abnormalities, may facilitate the development or application of an acceptable system of terminology.     

August Weismann's theory of the germ-plasm and the problem of unconceived alternatives

I have argued elsewhere that scientific realism is most significantly challenged neither by traditional arguments from underdetermination of theories by the evidence, nor by the traditional pessimistic induction, but by a rather different historical pattern: our repeated failure to conceive of alternatives to extant scientific theories, even when those alternatives were both (1) well-confirmed by the evidence available at the time and (2) sufficiently scientifically serious as to be later embraced by actual scientific communities. Here I use August Weismann's defense of his influential germ-plasm theory of inheritance to support my claim that this pattern characterizes the history of theoretical scientific investigation generally. Weismann believed that the germ-plasm must become disintegrated into its constituent elements over the course of development, I argue, only because he failed to conceive of any possible alternative mechanism of ontogenetic differentiation. This and other features of the germ-plasm theory, I suggest, reflect a still more fundamental failure to imagine that the germ-plasm might be a productive rather than expendable resource for the cell. Weismann's case provides impressive support for the problem of unconceived alternatives while rendering its challenge to scientific realism deeper and sharper in a number of important ways.     

A statistically valid alternative to the TDT

OBJECTIVE: To present an alternative linkage test to the transmission/disequilibrium test (TDT) which is conservative under the null hypothesis and generally more powerful under alternatives. METHODS: The exact distribution of the TDT is examined under both the null hypothesis and relevant alternatives. The TDT is rewritten in an alternate form based on the contributions from each of the three relevant parental mating types. This makes it possible to show that a particular term in the estimate is an exact tie and thus to rewrite the estimate without this term and to replace the multinomial 'variance estimate' of Spielman et al. [Am J Hum Genet 1993;52:506-516] by the binomial variance. RESULTS: The resulting test is shown to be a stratified McNemar test (SMN). The significance level attained by the SMN is shown to be conservative when compared to the asymptotic chi(2) distribution, while the TDT often exceeds the nominal level alpha. Under alternatives, the proposed test is shown to be typically more powerful than the TDT. CONCLUSION: The properties of the TDT as a statistical test have never been fully investigated. The proposed test replaces the heuristically motivated TDT by a formally derived test, which is also computationally simple.     

Making a robust biomolecular time scale for phylogenetic studies

The further evolution of informational molecular sequences should depend on the number of viable alternatives possible for the sequences as set by selection, the unrepaired mutation rate, and time. Most biomolecular clocks are based on Kimura's nearly neutral mutation random-drift hypothesis. This clock assumes that informational sequences are in equilibrium, i.e., the nucleotides mutate at a uniform rate and the number of nucleotides unconstrained by selection remains constant. Correcting for deviations from these assumptions should produce a more accurate clock. Informational molecules probably formed from polynucleotides having some other function such as nitrogen or nucleotide storage, thus being initially functionally unselected. At any time the rate of development of functionality in a protein may be expected to be proportional to the number of viable alternatives of sequence in its potentially interacting regions. Assuming the rate of unrepaired mutations is constant, these clocks should exponentially slow as they evolve, each with a different rate toward individual equilibria. Also if the degree of selection changes, its clock rate should change. For a more precise clock two approaches are suggested to estimate these time dependent changes in evolutionary rate. An improved clock could improve estimation of phylogeny and put a time scale on that phylogeny.     

Inverting the null-hypothesis of speciation: a marine snail perspective

Speciation is currently an intensely debated topic, much more so than 20–30 years ago when most biologists held the view that new species (at least of animals) were formed through the split of evolutionary lineages by the appearance of physical barriers to gene flow. Recent advances have, however, lent both theoretical and empirical support to speciation in the presence of gene flow. Nevertheless, the allopatric hypothesis of speciation is still the default model. The consequence of this is that to support sympatric and parapatric modes of speciation all allopatric alternatives must be rejected, while an allopatric explanation is usually accepted without rejecting possible non-allopatric alternatives. However, classical cases of allopatric speciation can be challenged by alternative non-allopatric explanations, and this begs for a more respectful view of how to deal with all models of speciation. An appealing approach is studying parallel evolution of reproductive barriers, which allows for comparative approaches to distinguish between allopatric and non-allopatric events, and explicit tests of a suitable null-hypothesis. Parallel evolution of reproductive isolation in a strongly polymorphic marine snail species serves as an illustrative example of such an approach. In conclusion, a more balanced debate on allopatric and non-allopatric speciation is needed and an urgent issue is to treat both allopatric and nonallopatric hypotheses critically, rather than using allopatry as the default model of speciation.     

Vaccines against gastrointestinal nematode parasites of ruminants

A consequence of intensive livestock production is an increase in the incidence and impact of gastrointestinal (GI) parasites. Farmers have sought to redress this shift in the natural host-parasite relationship by chemotherapy. However, with the widespread development of resistance to anthelmintics and the current impetus for sustainable agricultural practices, alternatives such as vaccines are being sought to maintain animal productivity. In this article, David Emery and Barry Wagland discuss recent advances in immunity to nematode infections of ruminants and the development of vaccines made possible by the dogged persistence and ingenuity of cadres of parasitologists who have done more than 'go through the motions'.     

Can science justify regulatory decisions about the cultivation of transgenic crops?

Results of scientific studies are sometimes claimed to provide scientific justification for regulatory decisions about the cultivation of certain transgenic crops. A decision may be scientifically justified if objective analysis shows that the decision is more likely than alternatives to lead to the achievement of specific policy objectives. If policy objectives are not defined operationally, as is often the case, scientific justification for decisions is not possible. The search for scientific justification for decisions leads to concentration on reducing scientific uncertainty about the behaviour of transgenic crops instead of reducing uncertainty about the objectives of policies that regulate their use. Focusing on reducing scientific uncertainty at the expense of clarifying policy objectives may have detrimental effects on scientists, science and society.     

Targeting tumors with peptides from natural sources

Peptide-based therapies offer the potential for non-genotoxic, genotype-specific alternatives, or adjuvants, to the current range of traditional cancer treatments. Such a patient-tailored cancer-cell-directed therapeutic approach should have fewer side effects and could well be more effective than the current drug- or combination-based regimens. Here, we review the potential of novel natural anticancer peptides such as necrotic peptides, apoptotic peptides, function-blocking peptides, antiangiogenic peptides and immunostimulatory peptides in the context of their ability to induce tumor regression. We focus on the therapeutic prospects of anticancer peptides and their possible application in tumor therapy.     

Is ACCTRAN better than DELTRAN?

When parsimony ancestral character reconstruction is ambiguous, it is often resolved in favour of the more complex character state. Hence, secondary loss (secondary “absence”) of a complex feature is favoured over parallel gains of that feature as this preserves the stronger hypothesis of homology. We believe that such asymmetry in character state complexity is important information for understanding character evolution in general. However, we here point out an inappropriate link that is commonly made between this approach and the accelerated transformation (ACCTRAN) algorithm. In ACCTRAN, changes are assigned along branches of a phylogenetic tree as close to the root as possible. This has been taken to imply that ACCTRAN will minimize hypotheses of parallel origins of complex traits and thus that ACCTRAN is philosophically better justified than the alternatives, such as delayed transformation (DELTRAN), where changes are assigned along branches as close to the tips as possible. We provide simple examples to show that such views are mistaken and that neither ACCTRAN nor DELTRAN consistently minimize parallel gain of complex traits. We therefore do not see theoretical grounds for favouring the popular ACCTRAN algorithm. © The Willi Hennig Society 2008.     

A quantitative investigation of the chemical space surrounding amino acid alphabet formation

To date, explanations for the origin and emergence of the alphabet of amino acids encoded by the standard genetic code have been largely qualitative and speculative. Here, with the help of computational chemistry, we present the first quantitative exploration of nature's “choices” set against various models for plausible alternatives. Specifically, we consider the chemical space defined by three fundamental biophysical properties (size, charge, and hydrophobicity) to ask whether the amino acids that entered the genetic code exhibit a higher diversity than random samples of similar size drawn from several different definitions of amino acid possibility space.We found that in terms of the properties studied, the full, standard set of 20 biologically encoded amino acids is indeed significantly more diverse than an equivalently sized group drawn at random from the set of plausible, prebiotic alternatives (using the Murchison meteorite as a model for pre-biotic plausibility). However, when the set of possible amino acids is enlarged to include those that are produced by standard biosynthetic pathways (reflecting the widespread idea that many members of the standard alphabet were recruited in this way), then the genetically encoded amino acids can no longer be distinguished as more diverse than a random sample. Finally, if we turn to consider the overlap between biologically encoded amino acids and those that are prebiotically plausible, then we find that the biologically encoded subset are no more diverse as a group than would be expected from a random sample, unless the definition of “random sample” is adjusted to reflect possible prebiotic abundance (again, using the contents of the Murchison meteorite as our estimator). This final result is contingent on the accuracy of our computational estimates for amino acid properties, and prebiotic abundances, and an exploration of the likely effect of errors in our estimation reveals that our results should be treated with caution. We thus present this work as a first step in quantifying and thus testing various origin-of-life hypotheses regarding the origin and evolution of life's amino acid alphabet, and advocate the progress that would add valuable information in the future.     

On classifying observations when one population is a mixture of normals

Some simple models for the mixture of distribution problems are considered. Two possible alternatives to the rather complex optimal discriminant function rule are mentioned. The performance of the BC method is never as satisfactory as the QDF method and in some cases it is far worse than the QDF method. The QDF can be used whenever sufficient numbers of observations are available to provide reasonably good estimates of means and covariances.     

Evidence that purifying selection acts on promoter sequences

We tested whether functionally important sites in bacterial, yeast, and animal promoters are more conserved than their neighbors. We found that substitutions are predominantly seen in less important sites and that those that occurred tended to have less impact on gene expression than possible alternatives. These results suggest that purifying selection operates on promoter sequences.     

Integrated Environmental and Economic Assessment of Products and Processes

The eco-efficiency analysis method developed and used by the Öko-Institut analyzes different alternatives that fulfill a defined consumer need, from an environmental as well as an economic perspective.
Like life-cycle assessment (LCA), eco-efficiency analysis makes possible the setting of priorities in purchasing decisions or can be used to show optimization potentials in product development processes.
Eco-efficiency analysis builds upon two methods: LCA, according to ISO 14040 ff. (to assess the environmental aspects of products and processes), and life-cycle costing. Life-cycle costing results in a single figure—the total costs of ownership to one or several actors. The environmental impacts can be evaluated and aggregated as a single score or the impact category indicator results can be kept separate. In either case two single scores can be compared: the total environmental burden or the impact category indicator results, and the total costs of ownership of the alternatives under consideration.
The results can then be plotted in two-dimensional graphs that show the effectiveness of certain measures in environmental and economic terms. The efficiency is expressed as a numerical ratio of environmental savings to difference in costs.
Together with furnishing more detailed results and a discussion of additional benefits or potential barriers, eco-efficiency analysis broadens the basis for decision-making processes.     

Detrimental impacts of radiotransmitters on juvenile Louisiana Waterthrushes

ABSTRACT.   The Louisiana Waterthrush (waterthrush; Seiurus motacilla ) is a forest-dwelling, Nearctic-Neotropical migratory passerine that nests along streams. We attached radiotransmitters (0.6–0.8 g) to 12 nestling waterthrushes using snug, elastic loops. At three nests, adult waterthrushes were videotaped removing radio-tagged young from the nest. In addition, we recovered nine radio-backpacks (with two still attached to the carcasses of nestlings) near nests within a few days after attaching transmitters. Only one of 12 radio-tagged young was relocated more than 24 h after attaching the transmitter. Thus, the method of transmitter attachment we used was not effective. Using snug, nonelastic loops (e.g., nylon) for the harness may reduce the loss of transmitters, but may injure the skin as fledglings grow. Other possible alternatives include (1) gluing the transmitter to skin on the back of nestlings, (2) capturing fledglings in mist nets and attaching transmitters a week or more after fledging by which time contour feathers have grown and the likelihood of a parent removing the transmitter may be reduced, or (3) attempting to monitor fledglings without attaching transmitters. The success of the latter two alternatives would likely be enhanced by attaching transmitters to adults and then tracking them to locate their still-dependent fledglings.     

THE ETHICS OF INTERCOUNTRY ADOPTION: WHY IT MATTERS TO HEALTHCARE PROVIDERS AND BIOETHICISTS

The goal of this paper is both modest and ambitious. The modest goal is to show that intercountry adoption should be considered by ethicists and healthcare providers. The more ambitious goal is to introduce the many ethical issues that intercountry adoption raises. Intercountry adoption is an alternative to medical, assisted reproduction option such as in vitro fertilization (IVF), intracytoplasmic sperm injection, third party egg and sperm donation and surrogacy. Health care providers working with assisted reproduction are in a unique position to introduce their clients to intercountry adoption; however, providers should only do so if intercountry adoption is ethically equal or superior to the alternatives. This paper first presents a brief history of intercountry adoption. The second section compares intercountry adoption with medical alternatives. The third section examines the unique ethical challenges that are not shared by other medical alternatives. The final section concludes that it is simplistic for a healthcare provider to promote intercountry adoption unconditionally; however, in situation where intercountry adoption is practiced conscientiously it poses no greater ethical concern than several medical alternatives. This conclusion is preliminary and is intended as a start for further discussion.     

A study of three IACUCs and their views of scientific merit and alternatives

Two ethical issues facing Institutional Animal Care and Use Committees [IACUCs] today are assessing scientific merit and the use of alternatives in research proposals. This study evaluated 3 IACUCs using a 19-question survey, with a 77.8% response rate. Although 76% of members answered that scientific merit should be more dili-gently assessed if more than slight pain is caused, 14% believed that assessing scien-tific merit is not the role of the IACUC. Nearly 86% agreed that the search for alterna-tives should be more diligent for protocols that incur more than slight pain to the animals involved. Some members believed that alternatives were not actively enough sought after, while others believed no viable alternatives existed. Additional guide-lines are needed to clarify these issues.     

Farnesyltransferase--new insights into the zinc-coordination sphere paradigm: evidence for a carboxylate-shift mechanism

Despite the enormous interest that has been devoted to the study of farnesyltransferase, many questions concerning its catalytic mechanism remain unanswered. In particular, several doubts exist on the structure of the active-site zinc coordination sphere, more precisely on the nature of the fourth ligand, which is displaced during the catalytic reaction by a peptide thiolate. From available crystallographic structures, and mainly from x-ray absorption fine structure data, two possible alternatives emerge: a tightly zinc-bound water molecule or an almost symmetrical bidentate aspartate residue (Asp-297beta). In this study, high-level theoretical calculations, with different-sized active site models, were used to elucidate this aspect. Our results demonstrate that both coordination alternatives lie in a notably close energetic proximity, even though the bidentate hypothesis has a somewhat lower energy. The Gibbs reaction and activation energies for the mono-bidentate conversion, as well as the structure for the corresponding transition state, were also determined. Globally, these results indicate that at room temperature the mono-bidentate conversion is reversible and very fast, and that probably both states exist in equilibrium, which suggests that a carboxylate-shift mechanism may have a key role in the farnesylation process by assisting the coordination/displacement of ligands to the zinc ion, thereby controlling the enzyme activity. Based on this equilibrium hypothesis, an explanation for the existing contradictions between the crystallographic and x-ray absorption fine structure results is proposed.