Genome-wide gene expression profiling of stress response in a spinal cord clip compression injury model.

BackgroundThe aneurysm clip impact-compression model of spinal cord injury (SCI) is a standard injury model in animals that closely mimics the primary mechanism of most human injuries: acute impact and persisting compression. Its histo-pathological and behavioural outcomes are extensively similar to human SCI. To understand the distinct molecular events underlying this injury model we analyzed global mRNA abundance changes during the acute, subacute and chronic stages of a moderate to severe injury to the rat spinal cord.ResultsTime-series expression analyses resulted in clustering of the majority of deregulated transcripts into eight statistically significant expression profiles. Systematic application of Gene Ontology (GO) enrichment pathway analysis allowed inference of biological processes participating in SCI pathology. Temporal analysis identified events specific to and common between acute, subacute and chronic time-points. Processes common to all phases of injury include blood coagulation, cellular extravasation, leukocyte cell-cell adhesion, the integrin-mediated signaling pathway, cytokine production and secretion, neutrophil chemotaxis, phagocytosis, response to hypoxia and reactive oxygen species, angiogenesis, apoptosis, inflammatory processes and ossification. Importantly, various elements of adaptive and induced innate immune responses span, not only the acute and subacute phases, but also persist throughout the chronic phase of SCI. Induced innate responses, such as Toll-like receptor signaling, are more active during the acute phase but persist throughout the chronic phase. However, adaptive immune response processes such as B and T cell activation, proliferation, and migration, T cell differentiation, B and T cell receptor-mediated signaling, and B cell- and immunoglobulin-mediated immune response become more significant during the chronic phase.ConclusionsThis analysis showed that, surprisingly, the diverse series of molecular events that occur in the acute and subacute stages persist into the chronic stage of SCI. The strong agreement between our results and previous findings suggest that our analytical approach will be useful in revealing other biological processes and genes contributing to SCI pathology

The genetics and genomics of Trypanosoma cruzi

Trypanosoma cruzi is a kinetoplastid parasite that causes Chagas disease. Trypanosomes are unusual organisms in many aspects of its genetics and molecular and cellular biology and considered a paradigm of the exception of the rule in the eukaryotic kingdom. The complete genome sequence of T. cruzi was published in 2005, thus, providing a major tool to the understanding of several of his unusual aspects. However, with so many different mechanisms between the parasite and its mammalian host there is still a lack of availability of effective antiparasitic drugs or disease treatments, specially in the chronic phase. This review highlights the fundamentals of the fasci- nating genetics and genomics of T. cruzi with emphasis in the differential mechanisms that could provide interesting therapeutic targets.Fil: Vazquez, Martin Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Investigaciones en Ingeniería Genética y Biología Molecular "Dr. Héctor N. Torres"; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentin

Current challenges in software solutions for mass spectrometry-based quantitative proteomics

This work was in part supported by the PRIME-XS project, grant agreement number 262067, funded by the European Union seventh Framework Programme; The Netherlands Proteomics Centre, embedded in The Netherlands Genomics Initiative; The Netherlands Bioinformatics Centre; and the Centre for Biomedical Genetics (to S.C., B.B. and A.J.R.H); by NIH grants NCRR RR001614 and RR019934 (to the UCSF Mass Spectrometry Facility, director: A.L. Burlingame, P.B.); and by grants from the MRC, CR-UK, BBSRC and Barts and the London Charity (to P.C.

The physiology of movement

Movement, from foraging to migration, is known to be under the influence of the environment. The translation of environmental cues to individual movement decision making is determined by an individual's internal state and anticipated to balance costs and benefits. General body condition, metabolic and hormonal physiology mechanistically underpin this internal state. These physiological determinants are tightly, and often genetically linked with each other and hence central to a mechanistic understanding of movement. We here synthesise the available evidence of the physiological drivers and signatures of movement and review (1) how physiological state as measured in its most coarse way by body condition correlates with movement decisions during foraging, migration and dispersal, (2) how hormonal changes underlie changes in these movement strategies and (3) how these can be linked to molecular pathways. We reveale that a high body condition facilitates the efficiency of routine foraging, dispersal and migration. Dispersal decision making is, however, in some cases stimulated by a decreased individual condition. Many of the biotic and abiotic stressors that induce movement initiate a physiological cascade in vertebrates through the production of stress hormones. Movement is therefore associated with hormone levels in vertebrates but also insects, often in interaction with factors related to body or social condition. The underlying molecular and physiological mechanisms are currently studied in few model species, and show -in congruence with our insights on the role of body condition- a central role of energy metabolism during glycolysis, and the coupling with timing processes during migration. Molecular insights into the physiological basis of movement remain, however, highly refractory. We finalise this review with a critical reflection on the importance of these physiological feedbacks for a better mechanistic understanding of movement and its effects on ecological dynamics at all levels of biological organization