Biological properties of two models of calcitonin gene related peptide with idealized amphiphilic alpha-helices of different lengths

Previous studies on calcitonin gene related peptide (CGRP) have demonstrated that it has the characteristics of an amphiphilic peptide, and from an examination of the sequence, we have proposed that it contains an amphiphilic alpha-helix. We have synthesized two analogues of CGRP which have different lengths of idealized amphiphilic alpha-helical secondary structure. The first model, CGRM-1, has been substituted with residues generating an idealized amphiphilic alpha-helix in the region between residues 8 and 25, equivalent to approximately five turns of an alpha-helix. This peptide is not an agonist in any of our bioassays, but it does bind with low affinity to rCGRP receptors in crude liver membranes. Our second model, CGRM-2, has an idealized amphiphilic alpha-helix between residues 8 and 18, which is equivalent to approximately three turns of an alpha-helix. In an in vitro rat vas deferens assay, this peptide is an agonist with a potency one-fourth that of the native hormone. However, the potency of CGRM-2 in an adenylate cyclase assay is much lower, only 1/140th the potency of CGRP. Both model peptides display amphiphilic characteristics commensurate with their design. We conclude that there is an amphiphilic alpha-helix in rCGRP between residues 8 and 18 and that this helix terminates in the vicinity of residue 18.     

The competitive ability of stem cells from mice with Hertwig's anemia

Mice homozygous for the gene, an, have a macrocytic, normochromic anemia. In this report, attempts have been made to cure Hertwig's anemia (an/an) by injecting genetically normal (+/+) stem cells. The anemia of unirradiated an/an mice was alleviated but not completely cured by injection of as many as 3 X 10(7) +/+ bone marrow cells. Lethal irradiation of the an/an recipients was necessary before injections of 10(7) +/+ marrow cells were effective in normalizing the blood parameters. The inability to achieve normal blood values without first destroying the host's own stem cells suggested that the indigenous an/an cells compete effectively with injected +/+ cells. This hypothesis was tested by injecting varying numbers of stem cells from C57BL/6J-+/+ mice, together with stem cells from either WBB6F1-an/an or, as controls, from their WBB6F1-+/+ littermates, into lethally irradiated hosts. The C57BL/6J and WBB6F1 mice have electrophoretically distinguishable hemoglobins. The an/an cells are able to compete in the repopulation of the host hematopoietic tissue as shown by the presence of WBB6F1 hemoglobin in the recipients. The cells from mice with Hertwig's anemia, however, do not compete as effectively as do the same number of cells from the +/+ littermates. These results indicate that the pluripotent hematopoietic stem cells of an/an mice are reduced in number, seeding capacity, or proliferative potential.     

Gametic and pleiotropic defects in mouse fetuses with Hertwig''s macrocytic anemia

Pleiotropic effects on germ cell number, hematologic status, and body size are described in 12- to 15-day WBB6F1 normal (+/-) and defective (an/an) mouse fetuses, with special emphasis on gametogenesis. Differences between genotypes were apparent by Day 12. At 12 days, normal testes contained many germ cells and frequent normal mitoses, and the number of germ cells increased rapidly from Day 12 to Day 15. By contrast, 12-day an/an testes contained fewer germ cells, frequently degenerating, and many abnormal mitoses. Their number of germ cells decreased rapidly, so that almost none persisted to Day 15. Normal ovaries contained many germ cells, with much normal mitosis on Day 12 and 13, followed by meioses, but the smaller an/an ovaries contained few germ cells, with little mitosis, some meiosis, and very much degeneration. The erythrocyte counts of both normal and anemic fetuses increased approximately fourfold between 12 and 15 days, but at comparable ages, total counts were always lower in an/an fetuses than in normal littermates. At all ages, Hertwig's anemic (an/an) fetuses were somewhat smaller than their normal littermates. Although both W/Wv and Sl/Sld mice also show macrocytic anemia and germ cell failure, the great difference in etiology of their germ cell defects indicates that an/an gene action must be qualitatively different from that in either W/Wv or Sl/Sld mice.     

Effects of ornithine or arginine administration on serum amino acid levels

In healthy humans after overnight fasting, an oral administration of ornithine induced a new steady state: an accumulation of serum alanine and proline, a decrease in serum valine concentration, transient reductions in serum urea and urinary urea contents, and then an increased urea excretion. On the other hand, an oral administration of arginine resulted in an anabolic state: decreases in serum leucine and isoleucine concentrations, reductions in serum glucose and free fatty acid contents and a rapid increase in serum insulin level. It was assumed that the effect of ornithine administration may be exerted through an activation of hepatic System A transport and that of arginine is an insulin-mediated action.     

Opposite allosteric mechanisms in TetR and CAP

Regulation of the DNA binding affinity of an oligomeric protein can be considered to consist of an intrinsic component, in which the affinity of an individual DNA‐binding domain is modulated in response to effector binding, and an extrinsic component, in which the relative position of the protein's two DNA‐binding domains are altered so that they can or cannot contact both half‐site operators simultaneously. We demonstrated directly that the TetR repressor utilizes an extrinsic mechanism and CAP, the catabolite activator protein, utilizes an intrinsic mechanism.     

Evolutionary stability: States and strategies

Different aspects and modifications of the definition of an evolutionarily stable (ES) strategy that have been considered in the literature can be incorporated in a unifying concept which regards the population context. This concept of evolutionary stability will generally characterize population states in both pure- and mixed-strategist models. In particular, it includes ES strategies, represented as a phenotype unique in an ES population. For an important class of mixed-strategist models, no strict ESS can exist. This will be the case whenever the success of an individual strategy is considered to follow as an average from the successes of its behavioural components. Instead, ESS results may be obtained from what will be called a “degenerate” form of the model, which is simply an ESS model on the level of elementary actions. Then, however, the correct interpretation of an ESS is not an individual phenotype but rather a population mixture of elementary actions. If an ES state exists in a mixed-strategist model it may be determined by an equilibrium condition; if there is an ES strategy, a different approach—mainly maximum considerations—is needed for finding it. An equilibrium condition does not hold for the components of an ES strategy straightforwardly; but it can be derived in terms of an auxiliary ESS model that considers first-order effects of the components. Several examples illustrate the significance of these results. Particularly, two models on “Games between Relatives” are reconsidered in order to display both their formal interrelation and the different meaning of their results in the context of mixed-strategist models.     

Effects of neurochemicals upon a dinoflagellate photoresponse.

Photoresponsiveness by Gymnodinium splendens Lebour was monitored quantitatively by a microscope-television system. Exposure to the catecholamines DOPA and Dopamine caused a decrease in light sensitivity, while 0.01 mM norepinephine, or isoproterenol did not affect photoresponsiveness. Classical catecholamine blocking agents, dichloroisoproterenol, propranolol, and dibenzyline, and an inhibitor of DOPA synthesis, alpha-methyl-rho-tyrosine, caused an increase in sensitivity. In addition, acetylcholine and an inhibitor of acetylcholinesterase activity, eserine, caused an increase in sensitivity, while an inhibitor of acetylcholine action atropine, had the opposite effect. These experiments suggest that G. splendens may have an antagonistic catecholamine-cholinergic system which participates in regulating photosensitivity.     

An analysis of extended and exponentially-fed-batch cultures.

Under certain conditions it is shown that an extended culture is equivalent to an exponentially-fed-batch culture, that an exponentially-fed-batch culture (and an extended culture) can be maintained at a steady state and that an exponentially-fed-batch culture may be mimicked by a continuous-flow culture with a constant dilution rate. Operational conditions required to maintain steady states are specified.     

Enzymatic Synthesis of N-formyl-L-aspartyl-L-phenylalanine Methyl Ester (Aspartame Precursor) Utilizing an Extractive Reaction in Aqueous/Organic Biphasic Medium

N-Formyl-L-aspartyl-L-phenylalanine methyl ester (N-formyl aspartame, F-AspPheOMe) was synthesized enzymatically utilizing an extractive reaction in an aqueous/organic biphasic system. The N-formyl aspartame yield in a pure aqueous monophasic system was, in general, ca. 3% , however, it was over 80 % in a water/1-butanol biphasic system using a simultaneously extractive operation of an enzymatic reaction in an aqueous phase and a product separation from an aqueous to an organic phases.     

Sex-Specific Audience Effect in the Context of Mate Choice in Zebra Finches

Animals observing conspecifics during mate choice can gain additional information about potential mates. However, the presence of an observer, if detected by the observed individuals, can influence the nature of the behavior of the observed individuals, called audience effect. In zebra finches (Taeniopygia guttata castanotis), domesticated males show an audience effect during mate choice. However, whether male and female descendants of the wild form show an audience effect during mate choice is unknown. Therefore, we conducted an experiment where male and female focal birds could choose between two distinctive phenotypes of the opposite sex, an artificially adorned stimulus bird with a red feather on the forehead and an unadorned stimulus bird, two times consecutively, once without an audience and once with an audience bird (same sex as test bird). Males showed an audience effect when an audience male was present and spent more time with adorned and less time with unadorned females compared to when there was no audience present. The change in time spent with the respective stimulus females was positively correlated with the time that the audience male spent in front of its cage close to the focal male. Females showed no change in mate choice when an audience female was present, but their motivation to associate with both stimulus males decreased. In a control for mate-choice consistency there was no audience in either test. Here, both focal females and focal males chose consistently without a change in choosing motivation. Our results showed that there is an audience effect on mate choice in zebra finches and that the response to a same-sex audience was sex-specific.     

Hydra as a model organism for the study of morphogenesis

Pattern formation in hydra is controlled by two sets of morphogens: an activator and an inhibitor o f head and bud formation, and an activator and an inhibitor o f foot formation.     

Limiting Factors Impacting on Voluntary First Person Informed Consent in the Philippines

How well can institutional guidelines help ensure the dignity, rights, safety and well being of research participants in an underdeveloped country? In this paper I describe the limits of informed consent as an instrument for the protection of participants in the context of the Philippines. I bring to this paper my experiences as an advocate of rights, a member of an ethics review board, a researcher on the ethics of research and as an observer of the dynamics of clinical practice in an academic public teaching hospital of the University of the Philippines where I am professor.     

Evolutionary stable sets in mixed-strategist models

Evolutionary stable sets are used as an extension of the concept of an evolutionarily stable strategy (ESS). They have, as sets, essentially the same properties as ordinary ESSs. Here, ES sets are applied to the characterization of what will happen in an asexual population of mixed-strategists under frequency-dependent selection. Such a population will tend to establish some state, usually not a unique one, that belongs to an ES set. For an important class of widely used mixed-strategist models, ES sets are found to comprise just those population states that allow the possible behavioural acts to be equally successful, or, to put it more precisely, that establish an evolutionarily stable population strategy.     

Physical Attractiveness of an Animal Species as a Decision Factor for its Preservation

ABSTRACT

This experimental study examines how framing an animal species as endangered affects its perceived attractiveness and how an animal's perceived attractiveness affects support for its conservation. Undergraduate students were shown a flyer from a fictitious environmental organization pleading for the protection of either a bat or an ape. The flyer contained either no picture, a picture of an attractive member of its species, or a picture of an unattractive member of its species. For both species, an animal's attractiveness substantially increased support for its protection. There was also more support for saving the species that was larger in size and more resembled humans. In a second experiment, participants rated an unattractive animal as more attractive if it was framed as endangered. There was no such effect for an animal originally perceived as attractive. The implications of the results for environmental policy and conservation support are discussed.     

A serum facted by newborn calf serum.

An intraperitoneal injection of newborn calf serum (NBCS) into CRF Swiss mice causes an inflammatory reaction characterized by an increase in the number of macrophages in the peritoneal cavity and a concomitant monocytosis. The serum of such mice contains a monocytosis-inducing factor, as demonstrated by the intravenous injection of serum collected 18 (CalS18) and 24 hr (CalS24) after the intraperitoneal injection of NBCS. Serum from normal untreated mice, from mice given an intraperitoneal injection of sterile pyrogen-free saline, which does not cause an inflammatory reaction, or from mice 72 hr after an intraperitoneal injection of NBCS, when the inflammatory reaction has subsided, does not cause a monocytosis in test mice. Intravenous injection of CalS18 causes not only a monocytosis but also an increase in the number of promonocytes and bone marrow monocytes, suggesting an increased in the number of promonocytes and bone marrow monocytes, suggesting an increased production of monocytes. The effect of CalS18, CalS24 and CalS18 filtrate is specific for the mononuclear phagocytes, since only non-significant increases in the numbers of lymphocytes and granulocytes were observed. The active factor in CalS18 was shown to be different from the monocytosis-inducing factor present in NBCS. The monocytosis-inducing factor in CalS18 passes through an ultrafiltration membrane with an exclusion limit of 50,000 Daltons, so that the molecular weight must be below this value.     

The leaf-clipping display: A newly-discovered expressive gesture in wild chimpanzees

Chimpanzees of the Mahale Mountains, Tanzania were discovered to show an expressive gesture using leaves, termed as “leaf-clipping display”. This behavioural signal is directed by an adult male to an estrous female as a possessive behaviour, or by an adolescent male as a courtship display, or by an estrous female to an adolescent male also as a solicitation of copulation. The signal also is used toward human observers as a signal of food-demanding. This behaviour pattern might originate in a displacement tool-making behaviour in conflict situations. The leaf-clipping display has not been observed in any other chimpanzee populations studied, and may probably be one example of the tradition drift in wild chimpanzees.     

An Ecosystem Health Index for a large and variable river basin: Methodology,challenges and continuous improvement in Queensland’s Fitzroy Basin

Report cards are an increasingly popular method for summarising and communicating relative environmental performance and ecosystem health, including in aquatic environments. They are usually underpinned by an Ecosystem Health Index (EHI) that combines various individual indicators to produce an overall ecosystem health “score”. As a result of public water quality concerns, an integrated means of monitoring and reporting on aquatic ecosystem health was needed for the Fitzroy Basin in central Queensland, Australia. The Fitzroy Partnership for River Health was formed to address this need, and developed an EHI and report card for the Basin using existing monitoring data collected from various third parties including regulated companies operations and government. At 142,000 square kilometres, the Fitzroy Basin is the largest catchment draining to the World Heritage Listed Great Barrier Reef. The Fitzroy Basin provides an example of how to deliver an effective aquatic ecosystem health reporting system in a large and complex river basin. We describe the methodology used to develop an adaptive EHI for the Fitzroy Basin that addresses variability, complexity and scale issues associated with reporting across large areas. As well, we report how to manage the design and reporting stages given limitations in data collection and scientific understanding.