Modelling an outbreak of an emerging pathogen

To illustrate the usefulness of mathematical models to the microbiology and medical communities, we explain how to construct and apply a simple transmission model of an emerging pathogen. We chose to model, as a case study, a large (>8,000 reported cases) on-going outbreak of community-acquired meticillin-resistant Staphylococcus aureus (CA-MRSA) in the Los Angeles County Jail. A major risk factor for CA-MRSA infection is incarceration. Here, we show how to design a within-jail transmission model of CA-MRSA, parameterize the model and reconstruct the outbreak. The model is then used to assess the severity of the outbreak, predict the epidemiological consequences of a catastrophic outbreak and design effective interventions for outbreak control.     

Tauchbeobachtungen an Plankton und an Echostreuschichten

Zusammenfassung 1. Das Tauchen als Methode zur Untersuchung von Plankton und Echostreuschichten wird durch vier Beispiele erläutert: (a) Visuelle Beobachtungen an Wasserschichtungen und Grenzschichten durch Schwimmtaucher. (b) Untersuchung von Echostreuschichten durch Freitaucher, wobei sich ergab, daß angesammeltes biogenes Material in den untersuchten Sprung- beziehungsweise Streuschichten die Schallreflektion nicht beeinflußt. (c) Beobachtung von Großplankton und Feststellung von Planktonund Sestonkonzentrationen beim Tauchen mit dem Bathyscaph. (d) Untersuchung der Tiefenstreuschicht (deep scattering layer) durch Beobachtung der Vertikalwanderung bestimmter Arten des Großplanktons mit den Tauchbooten Bathyscaph und Soucoupe Plongeante. Physonectide Siphonophoren und Myctophiden standen in deutlicher Beziehung zur Tiefenstreuschicht und wurden als Echogeber erkannt.2. Die Möglichkeiten, von Tauchbooten aus quantitative und qualitative Proben von Plankton und auch vom Benthos zu nehmen, sind zur Zeit noch unzureichend. Die Entwicklung entsprechender Geräte für den wahlweisen und mehrfachen Einsatz bei demselben Tauchgang wird empfohlen.

---

Diving observations on plankton and on scattering layers

Diving techniques are employed as a research tool in plankton investigations carried out in shallow water of the western Baltic Sea. Observations and samplings were made by skin divers on scattering layers corresponding to the discontinuity layers. Biogene materials, sometimes concentrated at the thermocline, are not responsible for this special kind of scattering, but rather discontinuity of salinity and temperature (Lenz 1965). For observations in deep water the use of undersea vehicles is recommended. From the Bathyscaph and the diving saucer, single plankton organisms and plankton concentrations were observed (e. g.Bernard 1958); investigations on the deep scattering layer have shown physonectid siphonophores and myctophids to be scatterers (Barham 1966). The equipment for sampling plankton and benthos from undersea vehicles is poorly developed. We need urgently gear for quantitative and qualitative sampling and for manifold use during single dives, i. e., multiple sampling gear and magazins for storage of samples.

     

Inheritance of an oviposition behavior by an egg parasitoid

A quantitative genetic study revealed genetic and environmental sources of variance in percentage parasitism of European corn borer egg masses and secondary sex ratios by Trichogramma nubilale. Full and half-sib groups of T. nubilale were obtained from a nested mating design, which permitted the partitioning of the variance of T. nubilale parasitism of European corn borer egg masses into additive genetic variance, maternal/dominant variance and environmental variance. A mother-daughter regression of the percentage of an egg mass parasitized allowed a determination of the direction of a potential response to selection in the event of maternal effects. No or very little additive genetic effects were associated with the percentage of eggs within a mass parasitized and secondary sex ratios, but a significant amount of the variance for both traits had a maternal and/or dominant genetic source. The relationship between mothers and daughters in egg mass parasitism was positive, and 55.4% of the progeny of a given mother had behaviors that resemble their mother. Most of the variance had an environmental and/or unknown genetic source implying potentially high phenotypic plasticity associated with all these traits. The presence of maternal effects and phenotypic plasticity could have multiple and complex effects on progeny characters and potential responses to selection.     

Pandemic bounds for an epidemic on an infinite lattice

Exact results have previously been obtained concerning the spread of infection in continuous space contact models describing a class of multi-type epidemics. Pandemic lower and upper bounds were obtained for the spatial final size. Pandemic results have also been obtained for a discrete space model on the integer lattice using an infinite matrix formulation of the final size equations. However, the proof required restrictive constraints to be placed on the model parameters which do not hold in general and will not be valid when infection modifies behaviour. The purpose of this paper is to remove these constraints and give a general proof of the pandemic results for the multi-type epidemic on the lattice Z(N).     

Adaptation of an introduced host to an indigenous parasite

Introduction of striped bass to the west coast from the east coast of the U.S.A. provided the opportunity to study a recent host-parasite association in a marine system. An indigenous species of parasite was known to induce pathological changes in the introduced population. Because the west coast population has been in association with this pathogenic parasite more than 20 generations, we predicted that the host reaction of the west coast population would be less severe compared to that of the naive east coast stock of striped bass. This prediction was tested by conducting reciprocal infection experiments with east and west coast hosts and parasites. The group of west coast striped bass had a lower intensity of infection and exhibited less tissue damage compared to the group of east coast striped bass. We suggest that selection has acted only on the host and is driven by parasite-induced host mortality. This type of 1-sided selection is in contrast to present models of the evolution of host-parasite associations.     

An odorant derivative as an antagonist for an olfactory receptor

Different odorants are recognized by different combinations of G protein-coupled olfactory receptors, and thereby, odor identity is determined by a combinatorial receptor code for each odorant. We recently demonstrated that odorants appeared to compete for receptor sites to act as an agonist or an antagonist. Therefore, in natural circumstances where we always perceive a mixture of various odorants, olfactory receptor antagonism between odorants may result in a receptor code for the mixture that cannot be predicted from the codes for its individual components. Here we show that stored isoeugenol has an antagonistic effect on a mouse olfactory receptor, mOR-EG. However, freshly purified isoeugenol did not have an inhibitory effect. Instead, an isoeugenol derivative produced during storage turned out to be a potent competitive antagonist of mOR-EG. Structural analysis revealed that this derivative is an oxidatively dimerized isoeugenol that naturally occurs by oxidative reaction. The current study indicates that as odorants age, they decompose or react with other odorants, which in turn affects responsiveness of an olfactory receptor(s).     

Solvent-tolerance of fungi located on an interface between an agar plate and an organic solvent

While 6 by 20 of type culture fungi could grow on an interface between organic solvent (log P, 4.12) and agar plate, 13 by 20 of strains could form a large colony after the removal of more toxic solvent, such as styrene (log P, 2.95) and tert-butyl acetate (log P, 1.76) because of viability of spores on the interface.     

Multipole representation of an eccentric dipole and an eccentric double-layer

Recently a theorem for representing current generators in a volume conductor by the superposition of a central dipole, quadrupole, octopole, etc., has been established by G. C. K. Yeh, J. Martinek, and H. de Beaumont (Bull. Math. Biophysics,20, 203–16, 1958). This theorem makes possible the representation of any discrete or line, surface- or volume-distributed current source by a unique model which can be determined for each given case by surface potential measurements and closed form analysis. In this paper the multipole representations of an eccentric dipole and an eccentric double-layer are obtained in terms of the various parameters of the assumed singularities, and the contributions to surface potentials due to each of the multipoles are compared. Certain numerical results corresponding to those of E. Frank (Amer. Heart J.,46, 364–78, 1953) are carried out and compared. Furthermore, the multipole representation of a partially damaged double-layer is also determined and compared with that of an undamaged one. It is concluded that within the range of parameters corresponding to human subjects the higher-order multipoles can contribute significantly to the surface potentials compared with the dipole. This investigation was supported by the National Heart Institute under a research grant H-2263(c).     

Controlling tungiasis in an impoverished community: an intervention study

Background

In Brazil, tungiasis is endemic in some resource-poor communities where various domestic and sylvatic animals act as reservoirs for this zoonosis. To determine the effect of control measures on the prevalence and intensity of infestation of human and animal tungiasis, a repeated cross-sectional survey with intervention was carried out.

Methodology/Principal Findings

In a traditional fishing community in Northeast Brazil, humans and reservoir animals were treated, and premise-spraying using an insecticide was done, while a second fishing community served as a control. Both communities were followed up 10 times during a 12-month period. At baseline, prevalence of tungiasis was 43% (95% confidence interval [CI]: 35%–51%) and 37% (95% CI: 31%–43%) in control and intervention villages, respectively. During the study, prevalence of tungiasis dropped to 10% (95% CI: 8%–13%; p<0.001) in the intervention village, while the prevalence remained at a high level in the control village. However, after one year, at the end of the study, in both communities the prevalence of the infestation had reached pre-intervention levels. Whereas the intensity of infestation was significantly reduced in the intervention community (p<0.001), and remained low at the end of the study (p<0.001), it did not change in the control village.

Conclusion/Significance

Our study shows that a reduction of prevalence and intensity of infestation is possible, but in impoverished communities a long-lasting reduction of disease occurrence can only be achieved by the regular treatment of infested humans, the elimination of animal reservoirs, and, likely, through environmental changes.

Trial Registration

Controlled-Trials.com ISRCTN27670575     

Seprase: an overview of an important matrix serine protease

Seprase or Fibroblast Activation Protein (FAP) is an integral membrane serine peptidase, which has been shown to have gelatinase activity. Seprase has a dual function in tumour progression. The proteolytic activity of Seprase has been shown to promote cell invasiveness towards the ECM and also to support tumour growth and proliferation. Seprase appears to act as a proteolytically active 170-kDa dimer, consisting of two 97-kDa subunits. It is a member of the group type II integral serine proteases, which includes dipeptidyl peptidase IV (DPPIV/CD26) and related type II transmembrane prolyl serine peptidases, which exert their mechanisms of action on the cell surface. DPPIV and Seprase exhibit multiple functions due to their abilities to form complexes with each other and to interact with other membrane-associated molecules. Localisation of these protease complexes at cell surface protrusions, called invadopodia, may have a prominent role in processing soluble factors and in the degradation of extracellular matrix components that are essential to the cellular migration and matrix invasion that occur during tumour invasion, metastasis and angiogenesis.     

Oxygen consumption by mitochondria from an endotherm and an ectotherm

Comparisons of metabolic properties of mitochondria from an endothermic and an ectothermic vertebrate were performed. Oxygen (O2) consumption rates of liver mitochondria from laboratory mice and western fence lizard (Sceloporus occidentalis) were determined over a range of temperatures (10, 20, 30 and 37 degrees C) and in the presence of a variety of substrates. At 37 degrees C the O2 consumption rate of mouse mitochondria was 4-11 times higher than lizard mitochondria in the presence of five of eight substrates. This range of differences is similar to differences reported for O2 consumption of endothermic animals, tissues and cells over those of ectotherms. Thermal sensitivity of mitochondria was measured by calculation of Q10s for O2 consumption. Q10s were highest for mouse mitochondria overall. The range that showed the highest Q10s for the mouse mitochondria was 30-20 degrees C, whereas for the lizard mitochondria it was 20-10 degrees C. Thus, mitochondria from the ectotherm showed a lower degree of temperature sensitivity than did mitochondria from the endotherm. The preferred substrate for all mitochondria at all temperatures was succinate, but mouse mitochondria then showed some preference for alpha-ketoglutarate and citrate, whereas lizard mitochondria showed a preference for pyruvate and malate + pyruvate.     

Properties of an unusual DNA primase from an archaeal plasmid

Primases are specialized DNA-dependent RNA polymerases that synthesize a short oligoribonucleotide complementary to single-stranded template DNA. In the context of cellular DNA replication, primases are indispensable since DNA polymerases are not able to start DNA polymerization de novo.

The primase activity of the replication protein from the archaeal plasmid pRN1 synthesizes a rather unusual mixed primer consisting of a single ribonucleotide at the 5′ end followed by seven deoxynucleotides. Ribonucleotides and deoxynucleotides are strictly required at the respective positions within the primer. Furthermore, in contrast to other archaeo-eukaryotic primases, the primase activity is highly sequence-specific and requires the trinucleotide motif GTG in the template. Primer synthesis starts outside of the recognition motif, immediately 5′ to the recognition motif. The fidelity of the primase synthesis is high, as non-complementary bases are not incorporated into the primer.

     

Genetic consequences of an introduction-colonization process in an endangered butterfly species

From a theoretical point of view, the genetic consequences of foundation events are relatively well known but few field experimental data are available on this subject. At the beginning of the 1970s, a small number of Proclossiana eunomia females were released in a region where this glacial relict was absent. We report here the genetic aspects of the evolution of the populations generated by these translocations. Both enzyme electrophoresis and wing pattern morphometry disclosed a significant differentiation of the populations both with their mother population and within themselves. Field observations and enzyme data suggest a stepping-stone colonization process, but there is no significant isolation by distance at this stage of population establishment, as predicted by 32 model. Concerning phenotypic characters, there is a significant correlation between morphometric and geographical distances; this may be due to isolation by distance but the action of environmental gradients cannot be excluded. Our results show that this colonization, although induced with a low number of founders, was a success, despite a predicted loss of polymorphism.     

Allosteric control of an ionotropic glutamate receptor with an optical switch

The precise regulation of protein activity is fundamental to life. The allosteric control of an active site by a remote regulatory binding site is a mechanism of regulation found across protein classes, from enzymes to motors to signaling proteins. We describe a general approach for manipulating allosteric control using synthetic optical switches. Our strategy is exemplified by a ligand-gated ion channel of central importance in neuroscience, the ionotropic glutamate receptor (iGluR). Using structure-based design, we have modified its ubiquitous clamshell-type ligand-binding domain to develop a light-activated channel, which we call LiGluR. An agonist is covalently tethered to the protein through an azobenzene moiety, which functions as the optical switch. The agonist is reversibly presented to the binding site upon photoisomerization, initiating clamshell domain closure and concomitant channel gating. Photoswitching occurs on a millisecond timescale, with channel conductances that reflect the photostationary state of the azobenzene at a given wavelength. Our device has potential uses not only in biology but also in bioelectronics and nanotechnology.     

Application of an interferometric biosensor chip to biomonitoring an endocrine discruptor

RecombinantE. coli ACV 1003 (recA::lacZ) releasing β-galactosidase by a SOS regulon system, when exposed to DNA-damaging compounds, have been used to effectively monitor endocrine disruptors. Low enzyme activity of less than 10 units/mL, corresponding to a μg/L (ppb) range of an endocrine disruptor (tributyl tin, bisphenol A,etc.), can be rapidly determined, not by a conventional time-consuming and tedious enzyme assay, but by an alternative interferometric biosensor. Heavily boron-doped porous silicon for application as an interferometer, was fabricated by etching to form a Fabry-Perot fringe pattern, which caused a change in the refractive index of the medium including β-galactosidase. In order to enhance the immobilization of the porous silicon surface, a calyx crown derivative (ProLinker A) was applied, instead of a conventional biomolecular affinity method using biotin. This resulted in a denser linked formation. The change in the effective optical thickness versus β-galactosidase activity, showed a linear increase up to a concentration of 150 unit β-galactosidase/mL, unlike the sigmoidal increase pattern observed with the biotin.     

Fatal attack on an infant by an adult female tonkean macaque

We describe a fatal attack on a 10-month-old female infant by an adult female Tonkean macaque (Macaca tonkeana)in a semi-free-ranging group. During an intense conflict involving many group members, an adult female, the second most dominant in the group, attacked the infant of a lower-ranking female. The attacker remained near the victim for approximately 20 min, grabbing and biting it repeatedly, until the mother retrieved the infant. She died 2 days later. An autopsy revealed no lethal injury;the main cause of death was starvation or dehydration or both. We discuss social conditions under which a fatal attack by an adult female might occur.     

A case of an osteolytic lesion on an Italian Neanderthal jaw

This article describes an osteolytic odontogenetic lesion found on the mandible of a Neanderthal from the Middle Paleolithic site of Riparo Mezzena near the city of Verona (Italy). A pathology was revealed through X-ray and computerized-tomodensitometric examinations. This lesion was compared to present and sub-contemporary populations and indicates that it may have been of infectious origin, resulting from a bacterial invasion of the root canal of a coronal pulp exposure. The bacterial contamination may have resulted either from a traumatic fracture, a cavity, or extensive wear on the tooth.     

Mechanosensitivity as an integrative system in heart: an audit

This review examines a manifold of apparently loosely linked observations and mechanisms, from membrane to man, and assembles them to support the notion that mechanoelectric transduction is an integrative regulatory system in the heart. For this, the assemblage has to satisfy, at least to some extent, criteria that apply to other integrative regulatory systems such as the endocrine and nervous systems. The integrative effectors in the endocrine system are chemical linkages, circulating hormones: in the nervous system the linkage is a network of cables, nerve conduction and neurotransmitters. Mechanical integration is would be effected through mechanical machinery, cardiac contractile and hydraulic function with attendant stress and strain transmitted via "tensegrity". This can, through the cytoskeleton, begin with membrane integrins and transmit intracellularly for example via F actins to reach the rest of the membranous integrins. Further transmission to the organ is via cell-to-cell adhesion complexes and the extracellular matrix. This tensegrity facilitates integration of force and strain changes from area to area. In consequence, and analogous to the neurendocrine system, mechanoelectric transduction should, and does (1) operate at the molecular or membrane level--this would be via mechanotransducers affecting transmembrane ionic flow; (2) operate in the cell--to influence electrophysiology; (3) have a multicellular expression--e.g. mechanical distortion of one cell can raise intracellular calcium of an adjacent cell; (4) express in the intact organ--e.g. an increase in venous return hydraulically distends the sinoatrial node, steepening its pacemaker potential, thus increasing heart rate. It should also (5) demonstrate elements of a feedback system--"mechanoelectric feedback", and (6) interact with other systems--the cytoskeleton incorporates cell signalling complexes intersecting with other signal cascades. Finally, (7) it can malfunction to produce clinical abnormality--it contributes electrophysiologically to lethal cardiac arrhythmia. This anatomical and functional behaviour of mechanoelectric transduction could sanction the prospect of viewing it as analogous to the other integrative physiological systems.     

Reflectionless passage of an electromagnetic wave through an inhomogeneous plasma layer

An exactly solvable model is used as a basis to study the reflectionless passage of a transverse electromagnetic wave through an inhomogeneous plasma containing large-amplitude, small-scale (subwave-length) structures (in particular, opaque regions) that cannot be correctly described by approximate methods. It is shown that, during the reflectionless passage of an electromagnetic wave, strong wave field splashes can occur in certain plasma sublayers. The nonuniform spatial plasma density profile is characterized by a number of free parameters describing the modulation depth of the dielectric function, the characteristic sizes of the structures and their number, the thickness of the inhomogeneous plasma region, and so on. Such plasma density structures are shown to be very diverse when, e.g., a wave that is incident from vacuum propagates without reflection through a plasma layer (wave barrier transillumination). With the cubic nonlinearity taken into account, a one-dimensional problem of the nonlinear transillumination of an inhomogeneous plasma can be solved exactly.