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.     

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.     

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.     

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.     

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.     

Impact of UV-B radiation (290–320 nm) upon estuarine bacteria

Summary Effects of ultraviolet radiation on the development of metabolism of estuarine bacterial populations in laboratory microecosystems were studied. When compared with bacterial populations developing under an ultraviolet-deficient condition, the heterotrophic populations from microecosystems exposed to an ultraviolet-supplemented sprectrum displayed an overall decrease in total numbers, an increase in the proportion of pigmented cells, a decrease in the number of cellulolytic microorganisms and an increase in heterotrophic respiration. Ultraviolet radiation in the 290–320 nm waveband was the apparent stressful environmental parameter.     

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.     

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.     

Intestinal uptake of fatty acids, cholesterol and decanol in ileal resected rabbits: effect of Isocal and Portagen

Isocal, but not Portagen, is associated with increased villus surface area in control rabbits and in animals with an ileal resection. In control animals, Isocal feeding was associated with an increased in vitro jejunal uptake of short and medium-chain length fatty acids and cholesterol, whereas Portagen feeding was associated with a decline in the uptake of short-, medium- and long-chain fatty acids, but an increase in the uptake of cholesterol. In animals with an ileal resection both diets were associated with an increased uptake of long-chain fatty acids and cholesterol. These changes in lipid uptake are not explained by alterations in villus surface area or unstirred water layer resistance.     

Effects of Triiodothyronine (T3) Supplementation Upon Ozone-Induced Lung Injury

Ozone exposure results in an acute decrease in the serum levels of thyroid hormones; the physiologic sequelae of this are unclear. Whereas thyroid hormone supplementation appears to benefit pulmonary function in septic, oxyradical models of injury, thyroid hormone increases ozone toxicity. We demonstrated an increase in metabolic rate and pulmonary injury in lungs from ozone exposed, T₃ treated animals. This was evidenced by an increase in pulmonary weight gain, vascular perfusion pressure, and decrease in compliance in the supplemented animals. However, an increase in alkane generation, as an index of lipid peroxidation, was not seen in the ozone exposed, hormonally treated animals. This suggests that although thyroid hormone supplementation increases metabolic rate and ozone toxicity, an increased rate of lipid peroxidation plays a minimal role.     

Rights, indirect harms and the non-identity problem

The non‐identity problem is the problem of grounding moral wrongdoing in cases in which an action affects who will exist in the future. Consider a woman who intentionally conceives while on medication that is harmful for a fetus. If the resulting child is disabled as a result of the medication, what makes the woman's action morally wrong? I argue that an explanation in terms of harmful rights violations fails, and I focus on Peter Markie's recent rights‐based defense. Markie's analysis rests on the notion of an indirect harm, and I show that the calculation of an indirect harm relies on an improper baseline for the determination of whether or not an action adversely affects a patient's interests. I also defend an impersonal duty‐based analysis of the wrongdoing in non‐identity cases against an objection by Markie. I close by arguing that the rights‐based analysis is insensitive to context and that context is morally relevant in the determination of the moral valence of actions in cases of non‐identity. This failure provides a pro tanto reason to favor an impersonal duty‐based analysis of the wrongdoing in non‐identity cases.     

苜蓿丫纹夜蛾核型多角体病毒囊膜内核衣壳排列图式的电镜观察

核型多角体病毒有单核衣壳包埋型和多核衣壳包埋型之分,单核衣壳包埋型是在一个病毒囊膜内只包含一个核衣壳,而多核衣壳包埋型的特点是在一个病毒囊膜内包含有２个以上的核衣壳,由于多个核衣壳成束地被包装在同一个病毒囊膜内,又称病毒束［１,２］。Ｈｕｎｔｅｒ等表明在干果斑螟核型多角体病毒中,病毒囊膜内包含２～２３个核衣壳［３］。Ｆｒａｓｅｒ将苜蓿丫纹夜蛾核型多角体病毒接种于秋粘虫细胞系,超薄切片电镜观察,病毒囊膜内包含的核衣壳数变动于２～１７粒,但未研究其核衣壳在病毒囊膜内的排列结构［４］。本研究用苜蓿丫纹…     

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.     

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.     

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.     

Ionic and energetic changes at competence in the naturally transformable bacterium Streptococcus pneumoniae

Addition of competence factor extracts to trigger competence in a culture of Streptococcus pneumoniae induced an increase in the intracellular pH and the Na+ content of the bacteria without any change in the K+ pool or in the membrane potential. These ionic shifts were concomitant with a stimulation of glycolysis that resulted in an enhanced ATP pool. Thus, in transforming conditions, at extracellular pH 7.8, competent bacteria presented a particularly high energetic state resulting from an increase in delta pH and in the ATP pool, associated with an enhanced Na+ content. These features are discussed in the context of homeostasis regulation in response to an environmental stimulus.