Sequelae of Occult Aggression Disqualifying Young, Socially Housed, Female New Zealand White Rabbits (Oryctolagus cuniculus) from Participation in Dermal Toxicology Studies.

International animal welfare organizations and federal, regional, and institutional oversight bodies encourage social housing of gregarious species, such as New Zealand white rabbits (Oryctolagus cuniculus), to promote animal wellbeing in research, teaching, testing and farming settings. At our institution, 2 groups of female New Zealand white rabbits (approximate age, 11 wk; mean weight, 2.35 kg), compatibly paired at the vendor for 5 wk, were paired in caging or group-housed in a floor pen. The rabbits appeared compatible, demonstrating primarily affiliative behaviors throughout 6 wk of daily observations. However, occult aggression that occurred between daily observations or nocturnally resulted in skin wounding. The skin injuries, first identified during prestudy clipping of fur from the back of each rabbit 6 wk after arrival, disqualified every animal from participation in skin toxicology and muscle implantation studies. Success meeting scientific research requirements while promoting animal welfare and health when socially housing New Zealand white rabbits requires examining the behavioral repertoire of their wild counterparts, European rabbits. Factors including age, sex, and housing density influence territoriality, dominance hierarchy, social ranking, and natural, agonistic, injurious, behavioral tendencies. IACUC and other relevant oversight bodies, researchers, and animal care staff should consider this case study and the species-specific natural history of New Zealand white rabbits when assessing the harm and benefit of social housing in regard to research utility and animal welfare.

Two homolog wheat Glycogen Synthase Kinase 3/SHAGGY--like kinases are involved in brassinosteroid signaling.

BACKGROUND: Glycogen Synthase Kinase 3/SHAGGY-like kinases (GSKs) are multifunctional non-receptor ser/thr kinases. Plant GSKs are involved in hormonal signaling networks and are required for growth, development, light as well as stress responses. So far, most studies have been carried out on Arabidopsis or on other eudicotyledon GSKs. Here, we evaluated the role of TaSK1 and TaSK2, two homolog wheat (Triticum aestivum) GSKs, in brassinosteroid signaling. We explored in addition the physiological effects of brassinosteroids on wheat growth and development. RESULTS: A bin2-1 like gain-of-function mutation has been inserted respectively in one of the homoeologous gene copies of TaSK1 (TaSK1-A.2-1) and in one of the homoeologous gene copies of TaSK2 (TaSK2-A.2-1). Arabidopsis plants were transformed with these mutated gene copies. Severe dwarf phenotypes were obtained closely resembling those of Arabidopsis bin2-1 lines and Arabidopsis BR-deficient or BR-signaling mutants. Expression of BR downstream genes, SAUR-AC1, CPD and BAS1 was deregulated in TaSK1.2-1 and TaSK2.2-1 transgenic lines. Severe dwarf lines were partially rescued by Bikinin beforehand shown to inhibit TaSK kinase activity. This rescue was accompanied with changes in BR downstream gene expression levels. Wheat embryos and seedlings were treated with compounds interfering with BR signaling or modifying BR levels to gain insight into the role of brassinosteroids in wheat development. Embryonic axis and scutellum differentiation were impaired, and seedling growth responses were affected when embryos were treated with Epibrassinolides, Propiconazole, and Bikinin. CONCLUSIONS: In view of our findings, TaSKs are proposed to be involved in BR signaling and to be orthologous of Arabidopsis Clade II GSK3/SHAGGY-like kinases. Observed effects of Epibrassinolide, Propiconazole and Bikinin treatments on wheat embryos and seedlings indicate a role for BR signaling in embryonic patterning and seedling growth.

Identification and characterization of two wheat Glycogen Synthase Kinase 3/ SHAGGY-like kinases.

BACKGROUND: Plant Glycogen Synthase Kinase 3/ SHAGGY-like kinases (GSKs) have been implicated in numerous biological processes ranging from embryonic, flower, stomata development to stress and wound responses. They are key regulators of brassinosteroid signaling and are also involved in the cross-talk between auxin and brassinosteroid pathways. In contrast to the human genome that contains two genes, plant GSKs are encoded by a multigene family. Little is known about Liliopsida resp. Poaceae in comparison to Brassicaceae GSKs. Here, we report the identification and structural characterization of two GSK homologs named TaSK1 and TaSK2 in the hexaploid wheat genome as well as a widespread phylogenetic analysis of land plant GSKs. RESULTS: Genomic and cDNA sequence alignments as well as chromosome localization using nullisomic-tetrasomic lines provided strong evidence for three expressed gene copies located on homoeolog chromosomes for TaSK1 as well as for TaSK2. Predicted proteins displayed a clear GSK signature. In vitro kinase assays showed that TaSK1 and TaSK2 possessed kinase activity. A phylogenetic analysis of land plant GSKs indicated that TaSK1 and TaSK2 belong to clade II of plant GSKs, the Arabidopsis members of which are all involved in Brassinosteroid signaling. Based on a single ancestral gene in the last common ancestor of all land plants, paralogs were acquired and retained through paleopolyploidization events, resulting in six to eight genes in angiosperms. More recent duplication events have increased the number up to ten in some lineages. CONCLUSIONS: To account for plant diversity in terms of functionality, morphology and development, attention has to be devoted to Liliopsida resp Poaceae GSKs in addition to Arabidopsis GSKs. In this study, molecular characterization, chromosome localization, kinase activity test and phylogenetic analysis (1) clarified the homologous/paralogous versus homoeologous status of TaSK sequences, (2) pointed out their affiliation to the GSK multigene family, (3) showed a functional kinase activity, (4) allowed a classification in clade II, members of which are involved in BR signaling and (5) allowed to gain information on acquisition and retention of GSK paralogs in angiosperms in the context of whole genome duplication events. Our results provide a framework to explore Liliopsida resp Poaceae GSKs functions in development.

Hemimandibulectomy after bisphosphonate treatment for complex regional pain syndrome: a case report and review on the prevention and treatment of bisphosphonate-related osteonecrosis of the jaw.

BACKGROUND: The increase in reported cases of osteonecrosis of the jaw has increased the clinical significance of bisphosphonate therapeutic agents in the dentistry field. METHODS: We present a rare and severe case of bisphosphonate-related osteonecrosis of the jaw caused by medicamentous treatment of complex regional pain syndrome. This article reviews the current international prevention and treatment guidelines with regard to bisphosphonate treatment. RESULTS: Even rare indications for bisphosphonate treatment may lead to devastating effects on the patient. CONCLUSIONS: Dentists and physicians who prescribe bisphosphonates should be familiar with the side effects of these drugs and the management of these side effects. To prevent negative outcomes, it is important that there be a close collaboration among the doctors involved and that a thorough medical history is obtained; this is especially true because the range of indications for bisphosphonate treatment increases every year.

In vitro activities of faropenem, ertapenem, imipenem and meropenem against Borrelia burgdorferi s.l.

Little is known about the in vitro activity of penems and carbapenems against the spirochete Borrelia burgdorferi. Here, faropenem, ertapenem, imipenem and meropenem as well as the third-generation cephalosporin ceftriaxone and tobramycin were tested in vitro against 11 isolates of the B. burgdorferi sensu lato complex. On a microg/mL basis, ertapenem was the most potent carbapenem (minimal inhibitory concentration (MIC) range: 0.015-0.125 microg/mL), with in vitro activity comparable with that of ceftriaxone against Borrelia. These findings are supported by the results of time-kill experiments in a Borrelia afzelii skin isolate, demonstrating a >3 log10 unit (99.9%) reduction of the inoculum after 96 h of exposure to either drug at a concentration of three log2 unit dilutions above the respective MIC.

Logical properties of foundational relations in bio-ontologies.

OBJECTIVE: We compare the advantages of specifying the semantics of foundational relations in bio-medical terminology systems using different types of formal deductive systems: first-order logic (FOL) and description logics (DLs). METHOD: As our focus example, we use a terminology whose basic terms are supposed to designate proper parthood relations, subdivision relations, and surrounded-by relations. Each type of relation captures an important and distinct aspect of the spatial organization of anatomical structures: the general part-whole structure (proper parthood), the division of salient anatomical objects into discrete, tree-like structures (subdivision-of), and the nesting of anatomical objects into containers (surrounded-by). We show that all three types of relations are strict partial orderings (i.e., asymmetric and transitive). Ontologies whose purpose is to specify the semantics of terms referring to these types of relations must include axioms strong enough to formally distinguish among them. We compare the extent to which axioms characterizing proper parthood, subdivision, and surrounded-by relations can be represented in first-order logic and various description logics. CONCLUSIONS: The development of bio-medical ontologies requires a rigorous formal analysis of foundational relations. Different kinds of formal tools may be used in this process. Ideally, an analysis in a highly expressive language, such as first-order logic, should be worked out in conjunction with analyses in less expressive but computationally tractable deductive systems such as description logics.

The qualitative and time-dependent character of spatial relations in biomedical ontologies.

MOTIVATION: The formal representation of mereological aspects of canonical anatomy (parthood relations) is relatively well understood. The formal representation of other aspects of canonical anatomy, such as connectedness and adjacency relations between anatomical parts, their shape and size as well as the spatial arrangement of anatomical parts within larger anatomical structures are, however, much less well understood and represented in existing computational anatomical and bio-medical ontologies only insufficiently. RESULTS: In this article, we provide a methodology of how to incorporate this kind of information into anatomical and bio-medical ontologies by applying techniques of representing qualitative spatial information from Artificial Intelligence. In particular, we focus on how to explicitly take into account the qualitative and time-dependent character of these relations. As a running example, we use the human temporomandibular joint (TMJ). AVAILABILITY: Using the presented methodology, a formal ontology was developed which is accessible on http://www.ifomis.org/bfo/fol. This ontology may help to improve the logical and ontological rigor of bio-medical ontologies such as the OBO relation ontology.

Granularity, scale and collectivity: when size does and does not matter.

Bridging levels of "granularity" and "scale" are frequently cited as key problems for biomedical informatics. However, detailed accounts of what is meant by these terms are sparse in the literature. We argue for distinguishing two notions: "size range," which deals with physical size, and "collectivity," which deals with aggregations of individuals into collections, which have emergent properties and effects. We further distinguish these notions from "specialisation," "degree of detail," "density," and "connectivity." We argue that the notion of "collectivity"--molecules in water, cells in tissues, people in crowds, stars in galaxies--has been neglected but is a key to representing biological notions, that it is a pervasive notion across size ranges--micro, macro, cosmological, etc.--and that it provides an account of a number of troublesome issues including the most important cases of when the biomedical notion of parthood is, or is not, best represented by a transitive relation. Although examples are taken from biomedicine, we believe these notions to have wider application.

Biomedical ontologies: what part-of is and isn't.

Mereological relations such as part-of and its inverse has-part are fundamental to the description of the structure of living organisms. Whereas classical mereology focuses on individual entities, mereological relations in biomedical ontologies are generally asserted between classes of individuals. In general, this practice leaves some basic issues unanswered: type constraints of mereological relations, e.g., concerning artifacts and biological entities, the relation between parthood and time, inferred parts and wholes as well as a delimitation of parthood against spatial inclusion. Furthermore, mereological relations can be asserted not only between physical objects but also between biological processes and medical procedures. We analyze these ambiguities and make suggestions for a standardization of mereological relations in biomedical ontologies.

A formal theory for spatial representation and reasoning in biomedical ontologies.

OBJECTIVE: The objective of this paper is to demonstrate how a formal spatial theory can be used as an important tool for disambiguating the spatial information embodied in biomedical ontologies and for enhancing their automatic reasoning capabilities. METHOD AND MATERIALS: This paper presents a formal theory of parthood and location relations among individuals, called Basic Inclusion Theory (BIT). Since biomedical ontologies are comprised of assertions about classes of individuals (rather than assertions about individuals), we define parthood and location relations among classes in the extended theory Basic Inclusion Theory for Classes (BIT+Cl). We then demonstrate the usefulness of this formal theory for making the logical structure of spatial information more precise in two ontologies concerned with human anatomy: the Foundational Model of Anatomy (FMA) and GALEN. RESULTS: We find that in both the FMA and GALEN, class-level spatial relations with different logical properties are not always explicitly distinguished. As a result, the spatial information included in these biomedical ontologies is often ambiguous and the possibilities for implementing consistent automatic reasoning within or across ontologies are limited. CONCLUSION: Precise formal characterizations of all spatial relations assumed by a biomedical ontology are necessary to ensure that the information embodied in the ontology can be fully and coherently utilized in a computational environment. This paper can be seen as an important beginning step toward achieving this goal, but much more work along these lines is required.

New real-time PCR-based method for in vitro susceptibility testing of Anaplasma phagocytophilum against antimicrobial agents.

Up to now, only a few isolates of Anaplasma phagocytophilum have been tested for their susceptibility against a small number of antimicrobial agents. In addition, as with other fastidious or intracellular bacteria, the test methods are laborious and neither minimal inhibitory concentration (MIC) definitions, nor the test conditions and the inocula are standardised to date. A new 16S-rDNA-based real-time PCR assay has been developed and used under standardised conditions to analyse the activity of seven antimicrobial agents against two A. phagocytophilum isolates. After 72 h incubation, MICs were determined by software-assisted calculation of bacterial growth in samples and controls from semi-quantitative PCR results. In our study, the rank order of potency on a mg/l basis for the antimicrobial agents with enhanced in vitro activity against A. phagocytophilum was moxifloxacin (MIC: < or = 0.03 mg/l) > doxycycline (MIC: < or = 0.125 mg/l) > ciprofloxacin (MIC: 0.125 mg/l). Gentamicin, ampicillin, azithromycin and cethromycin showed no activity against the isolates tested in this investigation. Our new 16S-rDNA-PCR-based microdilution test system was shown to be sensitive, reproducible and reliable. The assay is capable of testing larger numbers of isolates and antimicrobial agents under standardised and very precise test conditions and may therefore offer a competent technical solution of the difficulties known to be associated with in vitro testing of other bacterial pathogens that grow intracellularly, such as chlamydia or rickettsia.

Hermite acuity gratings and models of space-variant acuity.

A coherent mathematical framework for the psychophysics of contrast perception emerges when contrast sensitivity is posed as an eigenvalue problem. This more general mathematical theory is broad enough to encompass Fourier analysis as it is used in vision research. We present a model of space-variant contrast detection to illustrate the main features of the theory, and obtain a new contrast sensitivity function using acuity gratings based on the Hermite functions. The Hermite gratings have several advantages: they represent a complete orthogonal basis, are easy to manipulate, and are of finite extent. A theoretical Hermite csf results from posing contrast perception as an eigenvalue problem. Surprisingly, the theoretical Hermite csf is determined by a single empirical parameter.