Absence of IFNγ expression induces neuronal degeneration in the spinal cord of adult mice

<p>Abstract</p> <p>Background</p> <p>Interferon gamma (IFNγ) is a pro-inflammatory cytokine, which may be up-regulated after trauma to the peripheral or central nervous system. Such changes include reactive gliosis and synaptic plasticity that are considered important responses to the proper regenerative response after injury. Also, IFNγ is involved in the upregulation of the major histocompatibility complex class I (MHC class I), which has recently been shown to play an important role in the synaptic plasticity process following axotomy. There is also evidence that IFNγ may interfere in the differentiation and survival of neuronal cells. However, little is known about the effects of IFNγ absence on spinal cord neurons after injury.</p> <p>Methods</p> <p>We performed a unilateral sciatic nerve transection injury in C57BL/6J (wild type) and IFNγ-KO (mutant) mice and studied motoneuron morphology using light and electron microscopy. One week after the lesion, mice from both strains were sacrificed and had their lumbar spinal cords processed for histochemistry (n = 5 each group) and transmission electron microscopy (TEM, n = 5 each group). Spinal cord sections from non-lesioned animals were also used to investigate neuronal survival and the presence of apoptosis with TUNEL and immunohistochemistry.</p> <p>Results</p> <p>We find that presumed motoneurons in the lower lumbar ventral horn exhibited a smaller soma size in the IFNγ-KO series, regardless of nerve lesion. In plastic embedded sections stained with toluidine blue, the IFNγ-KO mice demonstrated a greater proportion of degenerating neurons in the ventral horn when compared to the control series (p < 0.05). Apoptotic death is suggested based on TUNEL and caspase 3 immunostaining. A sciatic nerve axotomy did not further aggravate the neuronal loss. The cellular changes were supported by electron microscopy, which demonstrated ventral horn neurons exhibiting intracellular vacuoles as well as degenerating nuclei and cytoplasm in the IFNγ-KO mice. Adjacent glial cells showed features suggestive of phagocytosis. Additional ultrastructural studies showed a decreased number of pre-synaptic terminals apposing to motoneurons in mutant mice. Nevertheless, no statistical difference regarding the input covering could be detected among the studied strains.</p> <p>Conclusion</p> <p>Altogether, these results suggest that IFNγ may be neuroprotective and its absence results in neuronal death, which is not further increased by peripheral axotomy.</p

Functional renormalization group with a compactly supported smooth regulator function

The functional renormalization group equation with a compactly supported smooth (CSS) regulator function is considered. It is demonstrated that in an appropriate limit the CSS regulator recovers the optimized one and it has derivatives of all orders. The more generalized form of the CSS regulator is shown to reduce to all major type of regulator functions (exponential, power-law) in appropriate limits. The CSS regulator function is tested by studying the critical behavior of the bosonized two-dimensional quantum electrodynamics in the local potential approximation and the sine-Gordon scalar theory for d<2 dimensions beyond the local potential approximation. It is shown that a similar smoothing problem in nuclear physics has already been solved by introducing the so called Salamon-Vertse potential which can be related to the CSS regulator.Comment: JHEP style, 11 pages, 2 figures, proofs corrected, accepted for publication by JHE

A Minimal Model of Metabolism Based Chemotaxis

Since the pioneering work by Julius Adler in the 1960's, bacterial chemotaxis has been predominantly studied as metabolism-independent. All available simulation models of bacterial chemotaxis endorse this assumption. Recent studies have shown, however, that many metabolism-dependent chemotactic patterns occur in bacteria. We hereby present the simplest artificial protocell model capable of performing metabolism-based chemotaxis. The model serves as a proof of concept to show how even the simplest metabolism can sustain chemotactic patterns of varying sophistication. It also reproduces a set of phenomena that have recently attracted attention on bacterial chemotaxis and provides insights about alternative mechanisms that could instantiate them. We conclude that relaxing the metabolism-independent assumption provides important theoretical advances, forces us to rethink some established pre-conceptions and may help us better understand unexplored and poorly understood aspects of bacterial chemotaxis

Gene by environment QTL mapping through multiple trait analyses in blood pressure salt-sensitivity: identification of a novel QTL in rat chromosome 5

BACKGROUND: The genetic mechanisms underlying interindividual blood pressure variation reflect the complex interplay of both genetic and environmental variables. The current standard statistical methods for detecting genes involved in the regulation mechanisms of complex traits are based on univariate analysis. Few studies have focused on the search for and understanding of quantitative trait loci responsible for gene × environmental interactions or multiple trait analysis. Composite interval mapping has been extended to multiple traits and may be an interesting approach to such a problem. METHODS: We used multiple-trait analysis for quantitative trait locus mapping of loci having different effects on systolic blood pressure with NaCl exposure. Animals studied were 188 rats, the progenies of an F2 rat intercross between the hypertensive and normotensive strain, genotyped in 179 polymorphic markers across the rat genome. To accommodate the correlational structure from measurements taken in the same animals, we applied univariate and multivariate strategies for analyzing the data. RESULTS: We detected a new quantitative train locus on a region close to marker R589 in chromosome 5 of the rat genome, not previously identified through serial analysis of individual traits. In addition, we were able to justify analytically the parametric restrictions in terms of regression coefficients responsible for the gain in precision with the adopted analytical approach. CONCLUSION: Future work should focus on fine mapping and the identification of the causative variant responsible for this quantitative trait locus signal. The multivariable strategy might be valuable in the study of genetic determinants of interindividual variation of antihypertensive drug effectiveness

Expression Analysis of PAC1-R and PACAP Genes in Zebrafish Embryos

This study describes the expression of the pituitary adenylate cyclase-activating polypeptide (PACAP1 and PACAP2) and PAC1 receptor genes (PAC1a-R and PAC1b-R) in the brain of zebrafish (Danio rerio) during development. In situ hybridization of the 24- and 48-hpf embryos revealed that PACAP genes were expressed in the telencephalon, the diencephalon, the rhombencephalon, and the neurons in the dorsal part of the spinal cord. PACAP2 mRNA appears to be the most abundant form during brain development. The two PAC1-R subtypes showed a similar expression pattern: mRNAs were detected in the forebrain, the thalamus, and the rhombencephalon. However, in the tectum, only PAC1b-R gene was detected. These results suggest that, in fish, PACAP may play a role in brain development

Genetic control of Eucalyptus urophylla and E. grandis resistance to canker caused by Chrysoporthe cubensis

Chrysophorte cubensis induced canker occurs in nearly all tropical and subtropical regions where eucalypts are planted, causing losses in both wood quality and volume productivity, especially so in the warmer and more humid regions of Brazil. The wide inter and intra-specific genetic variability of resistance to canker among Eucalyptus species facilitates the selection of resistant plants. In this study, we evaluated resistance to this pathogen in five Eucalyptus grandis (G) and 15 E. urophylla (U) trees, as well as in 495 individuals from 27 progenies derived from crosses between the trees. In the field, six-months-old test seedlings were inoculated with C. cubensis. Lesion length in the xylem and bark was measured eight months later. The results demonstrated that xylem lesions could preferentially be used for the selection of resistant clones. Eight trees (7 U and 1 G) were susceptible, and the remainder (8 U and 4 G) resistant. Individual narrow and broad sense heritability estimates were 17 and 81%, respectively, thereby suggesting that canker resistance is quantitative and highly dependent on dominance and epistasis

Fifteen Year Outcome of the Ceraver Hermes Posterior-Stabilized Total Knee Arthroplasty: Safety of the Procedure with Experienced and Inexperienced Surgeons

We wished to determine whether total knee replacement (TKA) performed by young surgeons increased rates of mortality and complications compared with TKA performed by senior surgeons using the same model of arthroplasty. There were no significant pre-operative differences between the groups in terms of age, gender, height, weight, body mass index, diagnosis, comorbidity and duration of follow-up, which was a mean of 15 years in both groups. Hence, we assessed the 15 year survival of the first 150 Ceraver Posterior-Stabilized total knee arthroplasties undertaken by young surgeons (aged of less than 30 years) in formation in a single university hospital setting (Group B). We used survival curve analysis, with strict definitions regarding end-points, and evaluated a number of different endpoint criteria to assess the outcome and to compare the results with those obtained by the two seniors (aged of more than 40 years) with their 50 first implantations (Group A). The clinical results and survival rate of implants at intermediate to long-term follow-up were similar in both Groups. Kaplan-Meier survival analysis, with revision as the endpoint for failure, showed that the rate of survival at ten years was 96% (95% CI, 93 to 100) in both groups. At fifteen years the rate of survival was 91% (95% CI, 85 to 97) in group B, and 92% (95% CI, 90 to 94) in group A. The implant used in this series appears particularly safe since the usual complications observed with posterior stabilized arthroplasties were not observed even with young surgeons