Dynamics and bifurcation of a model for hormonal control of the menstrual cycle with inhibin delay

A system of 13 ordinary differential equations with 42 parameters is presented to model hormonal regulation of the menstrual cycle. For an excellent fit to clinical data, the model requires a 36 h time delay for the effect of inhibin on the synthesis of follicle stimulating hormone. Biological and mathematical reasons for this delay are discussed. Bifurcations with respect to changes in three important parameters are examined. One parameter represents the level of estradiol adequate for significant synthesis of luteinizing hormone. Bifurcation diagrams with respect to this parameter reveal an interval of parameter values for which a unique stable periodic solution exists and this solution represents a menstrual cycle during which ovulation occurs. The second parameter measures mass transfer between the first two stages of ovarian development and is indicative of healthy follicular growth. The third parameter is the time delay. Changes in the second parameter and the time delay affect the size of the uniqueness interval defined with respect to the first parameter. Saddle-node, transcritical and degenerate Hopf bifurcations are studied.     

Distal-to-proximal NO conversion in hemoproteins: the role of the proximal pocket

Hemoproteins play central roles in the formation and utilization of nitric oxide (NO) in cellular signaling, as well as in protection against nitrosative stress. Key to heme-nitrosyl function and reactivity is the Fe coordination number (5 or 6). For (five-coordinate) 5c-NO complexes, the potential for NO to bind on either heme face exists, as in the microbial cytochrome c′ from Alcaligenes xylosoxidans (AxCYTcp), which forms a stable proximal 5c-NO complex via a distal six-coordinate NO intermediate and a putative dinitrosyl species. Strong parallels between the NO-binding kinetics of AxCYTcp, the eukaryotic NO sensor soluble guanylate cyclase, and the ferrocytochrome c/cardiolipin complex have led to the suggestion that a distal-to-proximal NO switch could contribute to the selective ligand responses in gas-sensing hemoproteins. The proximal NO-binding site in AxCYTcp is close to a conserved basic (Arg124) residue that is postulated to modulate NO reactivity. We have replaced Arg124 by five different amino acids and have determined high-resolution (1.07-1.40 Å) crystallographic structures with and without NO. These, together with kinetic and resonance Raman data, provide new insights into the mechanism of distal-to-proximal heme-NO conversion, including the determinants of Fe-His bond scission. The Arg124Ala variant allowed us to determine the structure of an analog of the previously unobserved key 5c-NO distal intermediate species. The very high resolution structures combined with the extensive spectroscopic and kinetic data have allowed us to provide a fresh insight into heme reactivity towards NO, a reaction that is of wide importance in biology.     

Tip growth in xylogenic suspension cultures ofZinnia elegans L.: Implications for the relationship between cell shape and secondary-cell-wall pattern in tracheary elements

Summary The relationship between cell expansion, cortical microtubule orientation, and patterned secondary-cell-wall deposition was investigated in xylogenic cell suspension cultures ofZinnia elegans L. The direction of cell expansion in these cultures is pH dependent; cells elongate at pH 5.5–6.0, but expand isodiametrically at pH 6.5–7.0. Contrary to our expectations, indirect immunofluorescence revealed that cortical microtubules are oriented parallel to the long axis in elongating cells. Pulse labeling of the walls of isolated cells with the fluorochrome Tinopal LPW demonstrated that xylogenic Zinnia mesophyll cells elongate by tip growth in culture. These results confirm that cortical microtubules in developing tracheary elements reorient before bundling to form transverse cortical microtubule bands. This rearrangement may allow the secondary cell wall pattern to conform to cell shape, independent of the direction in which the cell was expanding prior to reorientation.Abbreviations CMT cortical microtubules - Mes 2-[N-morpholino]ethanesulfonic acid - TE tracheary element     

Does sexual experience affect the strength of male mate choice for high‐quality females in Drosophila melanogaster?

Although females are traditionally thought of as the choosy sex, there is increasing evidence in many species that males will preferentially court or mate with certain females over others when given a choice. In the fruit fly, Drosophila melanogaster, males discriminate between potential mating partners based on a number of female traits, including species, mating history, age, and condition. Interestingly, many of these male preferences are affected by the male''s previous sexual experiences, such that males increase courtship toward types of females that they have previously mated with and decrease courtship toward types of females that have previously rejected them. D. melanogaster males also show courtship and mating preferences for larger females over smaller females, likely because larger females have higher fecundity. It is unknown, however, whether this preference shows behavioral plasticity based on the male''s sexual history as we see for other male preferences. Here, we manipulate the sexual experience of D. melanogaster males and test whether this manipulation has any effect on the strength of male mate choice for large females. We find that sexually inexperienced males have a robust courtship preference for large females that is unaffected by previous experience mating with, or being rejected by, females of differing sizes. Given that female body size is one of the most common targets of male mate choice across insect species, our experiments with D. melanogaster may provide insight into how these preferences develop and evolve.     

The hows and whys of aerobic H2 metabolism

The bacterial [NiFe]-hydrogenases have been classified as either 'standard' or 'O2-tolerant' based on their ability to function in the presence of O2. Typically, these enzymes contain four redox-active metal centers: a Ni-Fe-CO-2CN- active site and three electron-transferring Fe-S clusters. Recent research suggests that, rather than differences at the catalytic active site, it is a novel Fe-S cluster electron transfer (ET) relay that controls how [NiFe]-hydrogenases recover from O2 attack. In light of recent structural data and mutagenic studies this article reviews the molecular mechanism of O2-tolerance in [NiFe]-hydrogenases and discusses the biosynthesis of the unique Fe-S relay.     

Calreticulin Induces Dilated Cardiomyopathy

Background

Calreticulin, a Ca²⁺-buffering chaperone of the endoplasmic reticulum, is highly expressed in the embryonic heart and is essential for cardiac development. After birth, the calreticulin gene is sharply down regulated in the heart, and thus, adult hearts have negligible levels of calreticulin. In this study we tested the role of calreticulin in the adult heart.

Methodology/Principal Findings

We generated an inducible transgenic mouse in which calreticulin is targeted to the cardiac tissue using a Cre/loxP system and can be up-regulated in adult hearts. Echocardiography analysis of hearts from transgenic mice expressing calreticulin revealed impaired left ventricular systolic and diastolic function and impaired mitral valve function. There was altered expression of Ca²⁺ signaling molecules and the gap junction proteins, Connexin 43 and 45. Sarcoplasmic reticulum associated Ca²⁺-handling proteins (including the cardiac ryanodine receptor, sarco/endoplasmic reticulum Ca²⁺-ATPase, and cardiac calsequestrin) were down-regulated in the transgenic hearts with increased expression of calreticulin.

Conclusions/Significance

We show that in adult heart, up-regulated expression of calreticulin induces cardiomyopathy in vivo leading to heart failure. This is due to an alternation in changes in a subset of Ca²⁺ handling genes, gap junction components and left ventricle remodeling.     

Survival and development of Pieris brassicae larvae upon application of sublethal doses of chlordimeform

Larvae of the large cabbage white butterfly, Pieris brassicae L. are important pests of cruciferous crops. Third and fifth instars were treated topically with sublethal doses of the formamidine pesticide chlordimeform. A number of excitable actions were induced but they did not persist beyond 24 hours. Following the initial period, however, subsequent development was delayed and mortality increased, particularly when third instars were treated. Dosing fifth-instar larvae caused few further deaths. A link is suggested between these results and the nutritional status of the insects, and they are discussed in terms of how they might contribute towards control.

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Résumé Les chenilles de troisième et cinquième stades de P. brassicae L. ont reçu une application superficielle de chlordiméforme, insecticide à la formamidine. Les doses inférieures à 335 g/g ont été sublétales, provoquant plusieurs formes d'excitation. Bien que leur comportement soit redevenu normal en 24 heures, les troisièmes stades traités ont eu leur développement retardé et une mortalité accrue. Le traitement des chenilles plus âgées a eu moins d'effets. Une relation est suggérée entre ces observations et le régime alimentaire de cet insecte; une réduction de l'alimentation, plus importante chez les chenilles de troisième que de cinquième stade de P. brassicae, accompagne le début des altérations du comportement provoquées par le chlordiméforme. La discussion porte sur le mécanisme de contrôle sublétal du chlordiméforme, impliquant des effects immédiats et retardés.

     

Observations on 6-mercaptopurine activity in Saccharomyces cerevisiae

Abstract Hydrogen fluoride treatment of [¹⁴C-glycerol]lipoteichoic acid synthesized by growing Streptococcus faecium ATCC9790 in the presence of 1,3[¹⁴C]glycerol produced five radioactive, water-soluble products which were identified by chromatographic and analytical techniques to be tetraglucosyl glycerol, triglucosyl glycerol, diglucosyl glycerol, monoglucosyl glycerol and unsubstituted glycerol. The percent composition of each varied modestly from culture to culture and ranged between 7 and 8% for the tetra-, 20.5 and 31.2% for the tri-, 11.3 to 23.5% for the di-, 20.9 to 26.8% for the mono-, and 23.1 to 34.8% for the unsubstituted glycerol. The same glucosylated glycerol compounds could be obtained in an in vitro reaction in which a 30 000 × g particulate enzyme catalyzed the incorporation of [³H]glucose from UDP [³H]glucose into lipoteichoic acid.