Stages of life: A new metaphysics of conceptionism

When a human being comes into existence is crucial in bioethics. Conceptionism is the view that a human being comes into existence at conception. The twinning argument is an influential objection to this view. All versions of the twinning argument rely on a metaphysics of material objects, namely, endurantism. Given this, a strategy for defending conceptionism against the twinning argument is to deny endurantism and adopt an alternative metaphysics of material objects. A version of this strategy which has been debated in this journal is to adopt perdurantism, or the ‘multiple occupancy view’, on which monozygotic twins share the zygote region as a temporal part. We present a novel version of this strategy: conceptionists can evade the twinning argument by adopting an exdurantist metaphysics of material objects. We suggest reasons for thinking that this is a plausible and, indeed, preferable way for conceptionists to avoid the twinning argument.     

Effect of Orientation of Fibers and Holes on the Radial Strain Amplification of Campaniform sensilla

##正## In this paper,a structural analysis is performed to gain insights on the synergistic mechanical amplification effect thatCampaniform sensilla have when combined in an array configuration.In order to simplify the analysis performed in this preliminaryinvestigation,an array of four holes in a single orthotropic lamina is considered.Firstly,a Finite Element Method(FEM) analysis is performed to discretely assess the influence that different geometrical parameters have on the mechanicalamplification properties of the array.Secondly,an artificial neural network is used to obtain an approximated multi-dimensionalcontinuous function,which models the relationship between the geometrical parameters and the amplification properties of thearray.Thirdly,an optimization is performed to identify the geometrical parameters yielding the maximum mechanical amplification.Finally,results are validated with an additional FEM simulation performed by varying geometrical parameters in theneighborhood of the identified optimal parameters.The method proposed in this paper can be fully automated and used to solvea wide range of optimization problems aimed at identifying optimal configurations of strain sensors inspired by Campaniformsensilla.     

Theoretical study of fluorescence of photosynthetic pigments at complex dependence of intensity of exciting light on time

Now the methods using the radiance with complex dependence of light intensity on time are applied to research of photosynthesis by means of fluorescence, exciting photosynthetic pigments. One of these methods is applied in PAM-fluorometers--the commercial devices currently widely used to investigate a state of photosynthesizing systems. However, if excitation is performed in this way, the question, what components of fluorescence are registered at an output of such devices, remains to be open-ended. In this work an attempt to analyse this task has been made.     

Inhibition of root elongation in microgravity by an applied electric field.

Roots grown in an applied electric field demonstrate a bidirectional curvature. To further understand the nature of this response and its implications for the regulation of differential growth, we applied an electric field to roots growing in microgravity. We found that growth rates of roots in microgravity were higher than growth rates of ground controls. Immediately upon application of the electric field, root elongation was inhibited. We interpret this result as an indication that, in the absence of a gravity stimulus, the sensitivity of the root to an applied electric stimulus is increased. Further space experiments are required to determine the extent to which this sensitivity is shifted. The implications of this result are discussed in relation to gravitropic signaling and the regulation of differential cell elongation in the root.     

The pathophysiology of brain edema in acute liver failure

Brain edema leading to intracranial hypertension is a cause of death in acute liver failure (ALF). The pathogenesis of this unique complication has been investigated in man, in experimental models and in isolated cell systems. From this experience, an integrated view has emerged, pointing at several mechanisms that contribute to cerebral swelling; an osmotic derangement in astrocytes, changes in cellular metabolism as well as alterations of cerebral blood flow. The ability of mild hypothermia to counteract each of these changes in experimental systems has supported the organization of a clinical trial of mild cooling in this disease. Such an advance can be viewed as the clinical translation of 20 years of research in this area.     

Inhibition of root elongation in microgravity by an applied electric field.

Roots grown in an applied electric field demonstrate a bidirectional curvature. To further understand the nature of this response and its implications for the regulation of differential growth, we applied an electric field to roots growing in microgravity. We found that growth rates of roots in microgravity were higher than growth rates of ground controls. Immediately upon application of the electric field, root elongation was inhibited. We interpret this result as an indication that, in the absence of a gravity stimulus, the sensitivity of the root to an applied electric stimulus is increased. Further space experiments are required to determine the extent to which this sensitivity is shifted. The implications of this result are discussed in relation to gravitropic signaling and the regulation of differential cell elongation in the root.     

The construction of the insect compound eye: the involvement of cell displacement and cell surface properties in the positioning of cells

The highly patterned arrangement of cells in the Ephestia compound eye arises in an orderly spatiotemporal sequence from a small population of cells organized into ommatidial precursors (“differentiation center”). The presumptive retina cells in the posterior region of this zone differentiate in an anterior to posterior order before differentiation proceeds in an anterior direction from the zone. The bidirectional growth of the compound eye from the differentiation center cannot be ascribed solely to an inductively transmitted “wave of differentiation”; the spreading of an epithelial sheet of cells bordering the center is, at least in part, involved in this process. This latter statement is based on the observation that when genetically marked tissues are transferred from the eye regions of donor pupae to the corresponding sites of host pupae, the grafts are displaced along the antero-posterior head axis, either in an anterior direction or a posterior direction depending upon their original positions relative to the differentiation center. The tissues derived from pupal grafts transposed or reoriented along this same axis often experience striking configurational changes and axial displacements. Findings of this nature support the hypothesis that cells of the prospective adult eye possess position-specific differences in cell adhesiveness.     

Genetic analysis of a Japanese family with normotriglyceridemic abetalipoproteinemia indicates a lack of linkage to the apolipoprotein B gene.

Normotriglyceridemic abetalipoproteinemia is a rare familial disorder characterized by an isolated deficiency of apoB-100. We have previously reported a patient with this disease, who had normal apoB-48 but no apoB-100. To elucidate the genetic abnormalities in this family, we studied the linkage of apoB gene using three genetic markers. The proband and her affected brother showed completely different apoB gene alleles, suggesting that the apoB gene itself is not related to this disorder in this family. By contrast, an American case had a point substitution in the apoB gene generating an in-frame stop codon. These results indicate that this disorder can be caused by defect(s) of either an apoB gene or other genes.     

The effect of collagen reinforcement in the behaviour of the temporomandibular joint disc

In this paper, the influence of collagen fibres in the behaviour of the temporomandibular joint disc is studied. A three-dimensional finite element model of the joint is developed from a set of medical images. The model comprises the mandible, part of the cranium and both temporomandibular joints. Joints have been considered to be composed of the articular discs and the temporomandibular ligaments. A fibre-reinforced porohyperelastic model was used to study the response under clenching of the fibrocartilage that composes the articular disc. This was divided in an intermediate zone, and two bands, an anterior and other posterior, in order to define the orientation of collagen fibres. The study demonstrates that the introduction of collagen fibres in the biphasic behaviour of the articular disc implies for a prescribed displacement not only an increase of the pressurization in the tissue, but also higher stresses in the anterior and posterior bands, as well as in the lateral zone of the disc. Thus, modelling the disc as an isotropic solid matrix leads in this case to an overestimation of the stresses in the intermediate zone, an underestimation of the pore pressure in this area, and an underestimation of the stresses in the rest of the disc.     

Molecular and biochemical characterisation of Mycobacterium smegmatis alcohol dehydrogenase C

The gene encoding of an alcohol dehydrogenase C (ADHC) from Mycobacterium smegmatis was cloned and sequenced. The protein encoded by this gene has 78% identity with Mycobacterium tuberculosis and Mycobacterium bovis BCG ADHC. The M. smegmatis ADHC was purified from M. smegmatis and the kinetic parameters of this enzyme showed that using NADPH as electron donor it has a strong preference for aliphatic and aromatic aldehyde substrates. Like the M. bovis BCG ADHC, this enzyme is more likely to act as an aldehyde reductase than as an alcohol dehydrogenase. The discovery of such an ADHC in a fast-growing, and easily engineered mycobacterial species opens the way to the utilisation of this M. smegmatis enzyme as a convenient model for the study of the physiological role of this alcohol dehydrogenase in mycobacteria.     

Function of a conserved residue in the amino terminal alpha-helix of four helical bundle cytokines

The Glu residue in the helix A is conserved among many cytokines. Mutation in this residue converts some cytokines to an antagonist. Such an artificial cytokine with an antagonist activity may be useful in a clinical area. In this study we generated a mutant granulocyte colony-stimulating factor (G-CSF) termed G-CSF.E20K in which this residue is substituted to Lys. It is known that G-CSF binds to a homodimeric receptor, while other cytokines which can be converted to antagonists bind to heterodimeric receptors. We showed that G-CSF.E20K does not bind to the receptor at all, and that it fails to stimulate proliferation. Thus, the mutant did not act as an antagonist. We propose that the nature of the receptor, namely whether it is a homodimer or heterodimer, determines the antagonist activity of the mutant.     

An insight into tumor dormancy equilibrium via the analysis of its domain of attraction

The trajectories of the dynamic system which regulates the competition between the populations of malignant cells and immune cells may tend to an asymptotically stable equilibrium in which the sizes of these populations do not vary, which is called tumor dormancy. Especially for lower steady-state sizes of the population of malignant cells, this equilibrium represents a desirable clinical condition since the tumor growth is blocked. In this context, it is of mandatory importance to analyze the robustness of this clinical favorable state of health in the face of perturbations. To this end, the paper presents an optimization technique to determine whether an assigned rectangular region, which surrounds an asymptotically stable equilibrium point of a quadratic systems, is included into the domain of attraction of the equilibrium itself. The biological relevance of the application of this technique to the analysis of tumor growth dynamics is shown on the basis of a recent quadratic model of the tumor–immune system competition dynamics. Indeed the application of the proposed methodology allows to ensure that a given safety region, determined on the basis of clinical considerations, belongs to the domain of attraction of the tumor blocked equilibrium; therefore for the set of perturbed initial conditions which belong to such region, the convergence to the healthy steady state is guaranteed. The proposed methodology can also provide an optimal strategy for cancer treatment.     

Improvement of Y-values of Hansenula polymorpha growth on methanol by simultaneous utilization of glucose

The simultaneous utilization of methanol and glucose by Hansenula polymorpha MH20 was investigated in chemostat (C-limited) cultivation. The mixed-substrate utilization results in biomass yields which are greater up to 20 to 25% as expected assuming an additive growth on both substrates. This is referred to as an auxiliary-substrate effect. Additionally, methanol can be utilized at higher growth rates in the presence of glucose compared to those obtained on this substrate alone. The extend of the auxiliary-substrate effect and the optimum ratio of substrates to reach this effect depend on dilution rate. The greatest stimulation in yield is obtained at D approximately 0.1 h-1, after raising the dilution rate this effect diminishes. At a rate of 0.1 h-1 the optimum mixed-substrate ratio of methanol: glucose is 7:1 (g). By increasing the growth rate the ratio changes toward glucose and reached a value of 1:1 (g) at D = 0.3 h-1. This change in the optimum ratio correlates with diminution in yield coefficient of methanol accompanying an increase in growth rate greater than 0.15 h-1. Energy balances of the utilization of the single substrates are used for interpretation of these results. From this it is evident that methanol does not play the role of an energy-rich substrate in the metabolism of yeast. Rather glucose is the energy-providing substrate in this combination.     

Implication of an unfavorable residue (Thr346) in intrinsic flexibility of firefly luciferase

In order to better understand the functional role of an unusual residue (Thr346) of firefly luciferase mutagenesis at this residue was performed. Firefly luciferase, catalyzes the bioluminescence reaction and is an excellent tool as a reporter in nano-system biology studies. Nonetheless, the enzyme rapidly loses its activity at temperatures above 30°C and this leads to reduced sensitivity and precision in analytical applications. Residue Thr346 in a connecting loop (341-348) of firefly luciferase is located in a disallowed region of Ramachandran plot. In this study, we have substituted this residue (T346) with anomalous dihedral angles with Val, Gly and Pro to clarify the role of this residue in structure and function of the enzyme using site-directed mutagenesis. Substitution of this unfavorable residue (T346) with atypical dihedral angles (ψ, φ) with other residues brought about an increase of thermostability and decrease of specific activity. Structural and functional properties of the mutants were analyzed using different spectroscopic methods. It seems that this residue is a critically conserved residue to support the functional flexibility for a fast kinetic bioluminescence reaction at the expense of lower stability.     

Pyridine nucleotide cycle of Salmonella typhimurium: in vitro demonstration of nicotinamide mononucleotide deamidase and characterization of pnuA mutants defective in nicotinamide mononucleotide transport.

The enzyme nicotinamide mononucleotide deamidase, an integral component of the proposed four-membered pyridine nucleotide cycle (PNC IV), has been demonstrated in extracts of Salmonella typhimurium LT2. The enzyme has an optimum pH of 8.7 and deamidates nicotinamide mononucleotide, forming nicotinic acid mononucleotide. Sigmoidal kinetic data suggest that this enzyme may be allosteric and therefore an important regulatory component of pyridine nucleotide cycle metabolism. Mutants previously designated pncC in anticipation of their lacking nicotinamide mononucleotide deamidase were examined and found to have normal levels of this enzyme. [14C]nicotinamide mononucleotide uptake studies, however, revealed a defect in the transport of this compound. Accordingly, the genetic designation for this locus was changed to pnuA to reflect its involvement in pyridine nucleotide uptake. Evidence is presented for the existence of two separate nicotinamide mononucleotide transport systems.     

Electrophoresis of isolated mitochondria

Isolated respiring mitochondria suspended in an isotonic medium migrate to the anode when they are exposed to an electric field. A simple method has been devised to visualize this electrical property of the organelles utilizing a modified zone electrophoresis technique. Uncouplers of oxidative phosphorylation inhibit this anaphoretic property of isolated mitochondria.     

The structure of the ostracode carapace

The carapace ultrastructure of three Recent [Heterocypris incongruens (Ramdohr), Cypridopsis uidua (Müller), and Conchoecia belgica Müller] and one Cretaceous ostracode species [Cypridea propunctata Sylvester-Bradley] has been studied by means of standard electron microscope techniques. The carapace is shown to be an organic structure divisible into an outer epicuticle, a median exocuticle and an inner endocuticle in the three cypridacean ostracodes examined. In Conchoecia belgica only an outer epicuticle and an inner endocuticle were observed, but this may be due to preservation. The chitin structure of the carapace of calcareous ostracodes is shown to be essentially an interlocking lattice, more coarsely developed in the exocuticle; layered (lamellar) chitin is only present in the selvage and in the connective tissue joining the valves at the hinge. The non-calcareous Conchoecia belgica possesses the layered chitin structure common to other crustaceans and to insects. The relationship of the carapace structure to that present in the decapod and insect exoskeleton is discussed. The technical problems met with during this study are considered in order to outline the difficulties associated with the study of organisms of this size.     

Ultimate Use of Two-Photon Fluorescence Microscopy to Map Orientational Behavior of Fluorophores

The orientational distribution of fluorophores is an important reporter of the structure and function of their molecular environment. Although this distribution affects the fluorescence signal under polarized-light excitation, its retrieval is limited to a small number of parameters. Because of this limitation, the need for a geometrical model (cone, Gaussian, etc.) to effect such retrieval is often invoked. In this work, using a symmetry decomposition of the distribution function of the fluorescent molecules, we show that polarized two-photon fluorescence based on tunable linear dichroism allows for the retrieval of this distribution with reasonable fidelity and without invoking either an a priori knowledge of the system to be investigated or a geometrical model. We establish the optimal level of detail to which any distribution can be retrieved using this technique. As applied to artificial lipid vesicles and cell membranes, the ability of this method to identify and quantify specific structural properties that complement the more traditional molecular-order information is demonstrated. In particular, we analyze situations that give access to the sharpness of the angular constraint, and to the evidence of an isotropic population of fluorophores within the focal volume encompassing the membrane. Moreover, this technique has the potential to address complex situations such as the distribution of a tethered membrane protein label in an ordered environment.