Xenobiotic metabolism: a view through the metabolometer

The combination of advanced ultraperformance liquid chromatography coupled with mass spectrometry, chemometrics, and genetically modified mice provide an attractive raft of technologies with which to examine the metabolism of xenobiotics. Here, a reexamination of the metabolism of the food mutagen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine), the suspect carcinogen areca alkaloids (arecoline, arecaidine, and arecoline 1-oxide), the hormone supplement melatonin, and the metabolism of the experimental cancer therapeutic agent aminoflavone is presented. In all cases, the metabolic maps of the xenobiotics were considerably enlarged, providing new insights into their toxicology. The inclusion of transgenic mice permitted unequivocal attribution of individual and often novel metabolic pathways to particular enzymes. Last, a future perspective for xenobiotic metabolomics is discussed and its impact on the metabolome is described. The studies reviewed here are not specific to the mouse and can be adapted to study xenobiotic metabolism in any animal species, including humans. The view through the metabolometer is unique and visualizes a metabolic space that contains both established and unknown metabolites of a xenobiotic, thereby enhancing knowledge of their modes of toxic action.

[Musculoskeletal puncture, injection and infiltration: swiss rheumatologists' point of view]

Arthrocentesis, injection and infiltration of joints and soft tissues belong to the basic procedures in rheumatology. The indications and the practical performance are based on experience and tradition. Nowadays, a crucial reappraisal and adaption of indications and technical aspects appear important in the light of new evidence and technical developments. The main indications for puncture remain the search of an infectious arthritis and reduction of intra-articular pressure due to effusion. Good indications for the injection of glucocorticoids are inflammation in sterile joints and activated osteoarthritis. The local infiltration with corticosteroids in mechanically induced enthesopathies at the lateral epicondyle of the humerus or at the plantar fascia have to be questioned in the light of recent publications which show that this common practice is associated with a poorer outcome than without injection.

A global ”imaging” view on systems approaches in immunology

The immune system exhibits an enormous complexity. High throughput methods such as the "-omic'' technologies generate vast amounts of data that facilitate dissection of immunological processes at ever finer resolution. Using high-resolution data-driven systems analysis, causal relationships between complex molecular processes and particular immunological phenotypes can be constructed. However, processes in tissues, organs, and the organism itself (so-called higher level processes) also control and regulate the molecular (lower level) processes. Reverse systems engineering approaches, which focus on the examination of the structure, dynamics and control of the immune system, can help to understand the construction principles of the immune system. Such integrative mechanistic models can properly describe, explain, and predict the behavior of the immune system in health and disease by combining both higher and lower level processes. Moving from molecular and cellular levels to a multiscale systems understanding requires the development of methodologies that integrate data from different biological levels into multiscale mechanistic models. In particular, 3D imaging techniques and 4D modeling of the spatiotemporal dynamics of immune processes within lymphoid tissues are central for such integrative approaches. Both dynamic and global organ imaging technologies will be instrumental in facilitating comprehensive multiscale systems immunology analyses as discussed in this review.

Xenomelia: a social neuroscience view of altered bodily self-consciousness

Xenomelia, the "foreign limb syndrome," is characterized by the non-acceptance of one or more of one's own extremities and the resulting desire for elective limb amputation or paralysis. Formerly labeled "body integrity identity disorder" (BIID), the condition was originally considered a psychological or psychiatric disorder, but a brain-centered Zeitgeist and a rapidly growing interest in the neural underpinnings of bodily self-consciousness has shifted the focus toward dysfunctional central nervous system circuits. The present article outlays both mind-based and brain-based views highlighting their shortcomings. We propose that full insight into what should be conceived a "xenomelia spectrum disorder" will require interpretation of individual symptomatology in a social context. A proper social neuroscience of xenomelia respects the functional neuroanatomy of corporeal awareness, but also acknowledges the brain's plasticity in response to an individual's history, which is lived against a cultural background. This integrated view of xenomelia will promote the subfield of consciousness research concerned with the unity of body and self.

Hardystonite From the Desert View Mine, California

The fluorescent mineral hardystonite is confirmed in a specimen from the Desert View Mine, California. Hardystonite had been known only from Franklin, New Jersey for over 100 years.

Applied Developmental Psychology as an Implementation of the Life-Span View of Human Development

Application of knowledge about psychological development should, ideally, be theory based. As such, these applications represent “natural ontogenetic experiments”; the results of the evaluation of such interventions feed back to the theory, helping to support, falsify, or refine the ideas from the theory which led to the particular application. Such applied developmental intervention research is central within a currently popular perspective of life-span human development. Thus, applied developmental intervention research provides critical tests of such key concepts within this life-span perspective as: plasticity; multidirectionality; the synthesis of continuous and discontinuous processes across ontogeny; contextual embeddedness; and the role of individuals as agents in their own development. This paper elucidates some of the major features of the dynamic linkage between applied developmental psychology and this view of life-span human development. Key elements of this life-span perspective and the facts of developmental intervention, as seen from this perspective, are specified. Finally, the doctoral training program at the authors' institution is presented as one example of how this link may be institutionalized in the form of graduate education.