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.     

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.     

Implementation of an AI-assisted fragment-generator in an open-source platform

We recently reported a deep learning model to facilitate fragment library design, which is critical for efficient hit identification. However, our model was implemented in Python. We have now created an implementation in the KNIME graphical pipelining environment which we hope will allow experimentation by users with limited programming knowledge.

We report a deep learning model to facilitate fragment library design, which is critical for efficient hit identification, and an implementation in the KNIME graphical workflow environment which should facilitate a more codeless use.     

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.     

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).     

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.     

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.

     

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.     

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.     

Synthesis of an alpha-aminophosphonate nucleoside as an inhibitor of S-adenosyl-L-homocysteine hydrolase

A phosphonic acid analogue of S-adenosyl-L-homocysteine was prepared by a novel method and the epimeric mixture separated. Preliminary studies indicate that each epimer causes time-dependent inactivation of S-adenosyl-L-homocysteine hydrolase, however each presented distinct kinetic characteristics.     

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.     

Apparent facilitation of an invasive mealybug by an invasive ant

Summary In the southeast United States, the invasive ant Solenopsis invicta is known to derive important carbohydrate (honeydew) resources from mealybugs utilizing grasses. Most important appears to be an invasive mealybug, Antonina graminis. We studied whether this mealybug and a similar native species also benefit from association with S. invicta. We found that mealybug occurrence increases significantly with increasing proximity to S. invicta mounds, suggesting that mealybugs benefit as well. Mutual benefits derived by S. invicta and A. graminis are consistent with a hypothesis proposing that associations among invasive species can be important in their success at introduced locations.     

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.     

Synthetic peptide model of an essential region of an aminoacyl-tRNA synthetase

A 40 amino acid sequence of the unsolved structure of Escherichia coli alanine-tRNA synthetase is essential for tRNA binding and encodes an immunological determinant that cross-reacts with antibodies raised against a eukaryote (insect Bombyx mori) alanine enzyme. The secondary structure of this sequence is predicted to be an amphiphilic alpha-helix that includes one aspartyl and eight glutamyl side chain carboxyl groups. The antibody reactivity and the conformation of a synthetic peptide model of this region (Glu346 to Ser385) were investigated. In addition, double Arg----Gln and Leu----Ala substitutions were separately placed in the enzyme on the hydrophilic and hydrophobic face, respectively, of the predicted helix. These mutations conserve the polar/nonpolar character of each face and retain the potential for helix formation. Circular dichroism spectra of the synthetic peptide model demonstrate the potential for amphiphilic helix formation for the segment from Glu346 to Ser385. The behavior of the mutations in the enzyme, together with earlier data and immunological assays presented here, suggests that one face of the putative helix is an antigenic region of the surface of the enzyme where it contributes to the interaction with alanine tRNA and that the specific sequence of the helix is an important determinant of enzyme stability.     

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.     

Rapid evolution of a novel song and an increase in repertoire size in an island population of an Australian songbird

Cultural innovations are commonly noted in animals, but times of development of novel traits are usually unknown. We report here a novel song type arising in a bird population on an offshore island of Western Australia where the time of colonization of the island by the Western Gerygone Gerygone fusca is known. On the mainland, a single song type is widespread. On Rottnest Island, many individuals sing a different type of song and a number possess a repertoire of two song types: the standard song shared with the mainland and the novel song type not found on the neighbouring mainland. The novel song type found on Rottnest is so different in its syntactical structure that one could easily mistake it for that of a new species. The characteristic song of mainland birds is irregular in the frequencies at which the notes within a song are delivered. The novel song on Rottnest has a highly structured syntax with notes delivered at a strict and repeated sequence of frequencies resulting in a rhythmic musical sound. The species is known to have colonized Rottnest in about 1955. The new song type apparently developed rapidly by cultural evolution in the last 50 years.     

Observation of an arsenic adduct in an acetyl esterase crystal structure

The crystal structures of an acetyl esterase, HerE, and its complex with an inhibitor dimethylarsinic acid have been determined at 1.30- and 1.45-A resolution, respectively. Although the natural substrate for the enzyme is unknown, HerE hydrolyzes the acetyl groups from heroin to yield morphine and from phenyl acetate to yield phenol. Recently, the activity of the enzyme toward heroin has been exploited to develop a heroin biosensor, which affords higher sensitivity than other currently available detection methods. The crystal structure reveals a single domain with the canonical alpha/beta hydrolase fold with an acyl binding pocket that snugly accommodates the acetyl substituent of the substrate and three backbone amides that form a tripartite oxyanion hole. In addition, a covalent adduct was observed between the active site serine and dimethylarsinic acid, which inhibits the enzyme. This crystal structure provides the first example of an As-containing compound in a serine esterase active site and the first example of covalent modification of serine by arsenic. Thus, the HerE complex reveals the structural basis for the broad scope inhibition of serine hydrolases by As(V)-containing organic compounds.     

Dynamics and metamorphosis of an identifiable peptidergic neuron in an insect

Eclosion hormone (EH) is a 7000 Da peptide that triggers ecdysis behavior in insects. In the moth, Manduca sexta, EH is found in two pairs of ventromedial (VM) cells in the brain which send their axons down the ventral nerve cord to a neurohemal site in the proctodeal nerve in the larva and pupa. During adult development, these cells send axon collaterals to the corpora cardiaca where they form a new release site used for adult eclosion. Studies of bioassayable peptide during the 5th larval instar and the larval-pupal transformation revealed that after depletion at ecdysis, the VM cells showed a transient increase in EH found in their cell bodies and axons. By contrast, their terminals in the proctodeal nerve showed a gradual accumulation of peptide followed by a release of over 90% of the stored material at pupal ecdysis. In situ hybridization analysis on whole mounts of the brains showed that the VM cells always contained EH mRNA with increased accumulation during the larval and pupal molting periods with a slight decline just before ecdysis. High levels of EH mRNA were found in brains of diapausing pupae. During the first two-thirds of adult development, mRNA accumulated to high levels, then slowly declined until ecdysis. EH mRNA levels up to 3 days after adult eclosion. At no time was EH mRNA found in the lateral neurosecretory cell cluster previously reported to produce EH for adult eclosion. 1994 John Wiley & Sons, Inc.