Three-step pathway engineering results in more incidence rate and higher emission of nerolidol and improved attraction of Diadegma semiclausum

The concentration and ratio of terpenoids in the headspace volatile blend of plants have a fundamental role in the communication of plants and insects. The sesquiterpene (E)-nerolidol is one of the important volatiles with effect on beneficial carnivores for biologic pest management in the field. To optimize de novo biosynthesis and reliable and uniform emission of (E)-nerolidol, we engineered different steps of the (E)-nerolidol biosynthesis pathway in Arabidopsis thaliana. Introduction of a mitochondrial nerolidol synthase gene mediates de novo emission of (E)-nerolidol and linalool. Co-expression of the mitochondrial FPS1 and cytosolic HMGR1 increased the number of emitting transgenic plants (incidence rate) and the emission rate of both volatiles. No association between the emission rate of transgenic volatiles and their growth inhibitory effect could be established. (E)-Nerolidol was to a large extent metabolized to non-volatile conjugates

Quantitative determination of spring water quality parameters via electronic tongue

[EN] The use of a voltammetric electronic tongue for the quantitative analysis of quality parameters in spring water is proposed here. The electronic voltammetric tongue consisted of a set of four noble electrodes (iridium, rhodium, platinum, and gold) housed inside a stainless steel cylinder. These noble metals have a high durability and are not demanding for maintenance, features required for the development of future automated equipment. A pulse voltammetry study was conducted in 83 spring water samples to determine concentrations of nitrate (range: 6.9-115 mg/L), sulfate (32-472 mg/L), fluoride (0.08-0.26 mg/L), chloride (17-190 mg/L), and sodium (11-94 mg/L) as well as pH (7.3-7.8). These parameters were also determined by routine analytical methods in spring water samples. A partial least squares (PLS) analysis was run to obtain a model to predict these parameter. Orthogonal signal correction (OSC) was applied in the preprocessing step. Calibration (67%) and validation (33%) sets were selected randomly. The electronic tongue showed good predictive power to determine the concentrations of nitrate, sulfate, chloride, and sodium as well as pH and displayed a lower R-2 and slope in the validation set for fluoride. Nitrate and fluoride concentrations were estimated with errors lower than 15%, whereas chloride, sulfate, and sodium concentrations as well as pH were estimated with errors below 10%.The authors gratefully acknowledge the Ministerio de Economia y Competitividad and FEDER, providing funds amounting to (sic)664.525,75 for the project "Desarrollo de sistemas basados en lenguas electronicas para el control y monitorizacion del ciclo integral del agua" INNPACTO. IPT-2012-0069-310000. Moreover, the authors gratefully acknowledge the Ministerio de Economia y Competitividad and FEDER (projects MAT2015-64139-C4-1-R (MINECO/FEDER), MAT2015-64139-C4-3-R (MINECO/FEDER)), the Generalitat Valenciana (project PROMETEOII/2014/047), and CIBER-BBN (NANOPROBE project) for their financial support.Carbó-Mestre, N.; López-Carrero, J.; Garcia-Castillo, FJ.; Tormos, I.; Olivas, E.; Folch, E.; Alcañiz Fillol, M.... (2018). Quantitative determination of spring water quality parameters via electronic tongue. Sensors. 18(1):1-12. https://doi.org/10.3390/s18010040S112181Winquist, F., Olsson, J., & Eriksson, M. (2011). Multicomponent analysis of drinking water by a voltammetric electronic tongue. Analytica Chimica Acta, 683(2), 192-197. doi:10.1016/j.aca.2010.10.027Storey, M. V., van der Gaag, B., & Burns, B. P. (2011). Advances in on-line drinking water quality monitoring and early warning systems. Water Research, 45(2), 741-747. doi:10.1016/j.watres.2010.08.049Winquist, F. (2008). Voltammetric electronic tongues – basic principles and applications. Microchimica Acta, 163(1-2), 3-10. doi:10.1007/s00604-007-0929-2Garçon, L.-A., Genua, M., Hou, Y., Buhot, A., Calemczuk, R., Livache, T., … Hou, Y. (2017). A Versatile Electronic Tongue Based on Surface Plasmon Resonance Imaging and Cross-Reactive Sensor Arrays—A Mini-Review. Sensors, 17(5), 1046. doi:10.3390/s17051046Hou, Y., Genua, M., Tada Batista, D., Calemczuk, R., Buhot, A., Fornarelli, P., … Livache, T. (2012). Continuous Evolution Profiles for Electronic-Tongue-Based Analysis. Angewandte Chemie International Edition, 51(41), 10394-10398. doi:10.1002/anie.201205346Holmin, S., Spångeus, P., Krantz-Rülcker, C., & Winquist, F. (2001). Compression of electronic tongue data based on voltammetry — a comparative study. Sensors and Actuators B: Chemical, 76(1-3), 455-464. doi:10.1016/s0925-4005(01)00585-8Campos, I., Alcañiz, M., Aguado, D., Barat, R., Ferrer, J., Gil, L., … Vivancos, J.-L. (2012). A voltammetric electronic tongue as tool for water quality monitoring in wastewater treatment plants. Water Research, 46(8), 2605-2614. doi:10.1016/j.watres.2012.02.029Martı́nez-Máñez, R., Soto, J., Garcia-Breijo, E., Gil, L., Ibáñez, J., & Llobet, E. (2005). An «electronic tongue» design for the qualitative analysis of natural waters. Sensors and Actuators B: Chemical, 104(2), 302-307. doi:10.1016/j.snb.2004.05.022Garcia-Breijo, E., Atkinson, J., Gil-Sanchez, L., Masot, R., Ibañez, J., Garrigues, J., … Olguin, C. (2011). A comparison study of pattern recognition algorithms implemented on a microcontroller for use in an electronic tongue for monitoring drinking waters. Sensors and Actuators A: Physical, 172(2), 570-582. doi:10.1016/j.sna.2011.09.039Moreno, L., Merlos, A., Abramova, N., Jiménez, C., & Bratov, A. (2006). Multi-sensor array used as an «electronic tongue» for mineral water analysis. Sensors and Actuators B: Chemical, 116(1-2), 130-134. doi:10.1016/j.snb.2005.12.063Sipos, L., Kovács, Z., Sági-Kiss, V., Csiki, T., Kókai, Z., Fekete, A., & Héberger, K. (2012). Discrimination of mineral waters by electronic tongue, sensory evaluation and chemical analysis. Food Chemistry, 135(4), 2947-2953. doi:10.1016/j.foodchem.2012.06.021Braga, G. S., Paterno, L. G., & Fonseca, F. J. (2012). Performance of an electronic tongue during monitoring 2-methylisoborneol and geosmin in water samples. Sensors and Actuators B: Chemical, 171-172, 181-189. doi:10.1016/j.snb.2012.02.092Escobar, J. D., Alcaniz, M., Masot, R., Fuentes, A., Bataller, R., Soto, J., & Barat, J. M. (2013). Quantification of organic acids using voltammetric tongues. Food Chemistry, 138(2-3), 814-820. doi:10.1016/j.foodchem.2012.11.078Martínez-Bisbal, M. C., Loeff, E., Olivas, E., Carbó, N., García-Castillo, F. J., López-Carrero, J., … Soto, J. (2017). A Voltammetric Electronic Tongue for the Quantitative Analysis of Quality Parameters in Wastewater. Electroanalysis, 29(4), 1147-1153. doi:10.1002/elan.201600717Bonastre, A., Ors, R., Capella, J. V., Fabra, M. J., & Peris, M. (2005). In-line chemical analysis of wastewater: present and future trends. TrAC Trends in Analytical Chemistry, 24(2), 128-137. doi:10.1016/j.trac.2004.09.008Ivarsson, P., Johansson, M., Höjer, N.-E., Krantz-Rülcker, C., Winquist, F., & Lundström, I. (2005). Supervision of rinses in a washing machine by a voltammetric electronic tongue. Sensors and Actuators B: Chemical, 108(1-2), 851-857. doi:10.1016/j.snb.2004.12.088Garcia-Breijo, E., Peris, R. M., Pinatti, C. O., Fillol, M. A., Civera, J. I., & Prats, R. B. (2013). Low-Cost Electronic Tongue System and Its Application to Explosive Detection. IEEE Transactions on Instrumentation and Measurement, 62(2), 424-431. doi:10.1109/tim.2012.2215156Winquist, F., Wide, P., & Lundström, I. (1997). An electronic tongue based on voltammetry. Analytica Chimica Acta, 357(1-2), 21-31. doi:10.1016/s0003-2670(97)00498-4Campos, I., Sangrador, A., Bataller, R., Aguado, D., Barat, R., Soto, J., & Martínez-Máñez, R. (2014). Ammonium and Phosphate Quantification in Wastewater by Using a Voltammetric Electronic Tongue. Electroanalysis, 26(3), 588-595. doi:10.1002/elan.201300538Geladi, P., & Kowalski, B. R. (1986). Partial least-squares regression: a tutorial. Analytica Chimica Acta, 185, 1-17. doi:10.1016/0003-2670(86)80028-9Wold, S., Antti, H., Lindgren, F., & Öhman, J. (1998). Orthogonal signal correction of near-infrared spectra. Chemometrics and Intelligent Laboratory Systems, 44(1-2), 175-185. doi:10.1016/s0169-7439(98)00109-9Sjöblom, J., Svensson, O., Josefson, M., Kullberg, H., & Wold, S. (1998). An evaluation of orthogonal signal correction applied to calibration transfer of near infrared spectra. Chemometrics and Intelligent Laboratory Systems, 44(1-2), 229-244. doi:10.1016/s0169-7439(98)00112-9Rouhollahi, A., Rajabzadeh, R., & Ghasemi, J. (2006). Simultaneous determination of dopamine and ascorbic acid by linear sweep voltammetry along with chemometrics using a glassy carbon electrode. Microchimica Acta, 157(3-4), 139-147. doi:10.1007/s00604-006-0668-9Riahi, S., Ganjali, M., Moghaddam, A., Pourbasheer, E., & Norouzi, P. (2009). Development of a New Combined Chemometrics Method, Applied in the Simultaneous Voltammetric Determination of Cinnamic Acid and 3, 4-Dihydroxy Benzoic Acid. Current Analytical Chemistry, 5(1), 42-47. doi:10.2174/157341109787047925Palacios-Santander, J. M., Cubillana-Aguilera, L. M., Cocchi, M., Ulrici, A., Naranjo-Rodríguez, I., Seeber, R., & Hidalgo-Hidalgo de Cisneros, J. L. (2008). Multicomponent analysis in the wavelet domain of highly overlapped electrochemical signals: Resolution of quaternary mixtures of chlorophenols using a peg-modified Sonogel–Carbon electrode. Chemometrics and Intelligent Laboratory Systems, 91(2), 110-120. doi:10.1016/j.chemolab.2007.10.00

Quantitative expansion microscopy for the characterization of the spectrin periodic skeleton of axons using fluorescence microscopy

Fluorescent nanoscopy approaches have been used to characterize the periodic organization of actin,spectrin and associated proteins in neuronal axons and dendrites. This membrane-associated periodicskeleton (MPS) is conserved across animals, suggesting it is a fundamental component of neuronalextensions. The nanoscale architecture of the arrangement (190 nm) is below the resolution limitof conventional fluorescent microscopy. Fluorescent nanoscopy, on the other hand, requires costlyequipment and special analysis routines, which remain inaccessible to most research groups. Thisreport aims to resolve this issue by using protein-retention expansion microscopy (pro-ExM) to revealthe MPS of axons. ExM uses reagents and equipment that are readily accessible in most neurobiologylaboratories. We first explore means to accurately estimate the expansion factors of protein structureswithin cells. We then describe the protocol that produces an expanded specimen that can be examinedwith any fluorescent microscopy allowing quantitative nanoscale characterization of the MPS. Wevalidate ExM results by direct comparison to stimulated emission depletion (STED) nanoscopy. Weconclude that ExM facilitates three-dimensional, multicolor and quantitative characterization of theMPS using accessible reagents and conventional fluorescent microscopes.Fil: Martínez, Gaby F.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Gazal, Nahir Guadalupe. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Quassollo Infanzon, Gonzalo Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Szalai, Alan Marcelo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Del Cid Pellitero, Esther. No especifíca;Fil: Durcan, Thomas M.. No especifíca;Fil: Fon, Edward A.. No especifíca;Fil: Bisbal, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Stefani, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Unsain, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentin

Use of 1H and 31P HRMAS to evaluate the relationship between quantitative alterations in metabolite concentrations and tissue features in human brain tumour biopsies

[EN] Quantitative multinuclear high-resolution magic angle spinning (HRMAS) was performed in order to determine the tissue pH values of and the absolute metabolite concentrations in 33 samples of human brain tumour tissue. Metabolite concentrations were quantified by 1D 1 H and 31P HRMAS using the electronic reference to in vivo concentrations (ERETIC) synthetic signal. 1 H–1 H homonuclear and 1 H–31P heteronuclear correlation experiments enabled the direct assessment of the 1 H–31P spin systems for signals that suffered from overlapping in the 1D 1 H spectra, and linked the information present in the 1D 1 H and 31P spectra. Afterwards, the main histological features were determined, and high heterogeneity in the tumour content, necrotic content and nonaffected tissue content was observed. The metabolite profiles obtained by HRMAS showed characteristics typical of tumour tissues: rather low levels of energetic molecules and increased concentrations of protective metabolites. Nevertheless, these characteristics were more strongly correlated with the total amount of living tissue than with the tumour cell contents of the samples alone, which could indicate that the sampling conditions make a significant contribution aside from the effect of tumour development in vivo. The use of methylene diphosphonic acid as a chemical shift and concentration reference for the 31P HRMAS spectra of tissues presented important drawbacks due to its interaction with the tissue. Moreover, the pH data obtained from 31P HRMAS enabled us to establish a correlation between the pH and the distance between the N(CH3)3 signals of phosphocholine and choline in 1 H spectra of the tissue in these tumour samples.The authors acknowledge the SCSIE-University of Valencia Microscopy Service for the histological preparations. They also acknowledge Martial Piotto (Bruker BioSpin, France) for providing the ERETIC synthetic signal. Furthermore, they acknowledge financial support from the Spanish Government project SAF2007-6547, the Generalitat Valenciana project GVACOMP2009-303, and the E.U.'s VI Framework Programme via the project "Web accessible MR decision support system for brain tumor diagnosis and prognosis, incorporating in vivo and ex vivo genomic and metabolomic data" (FP6-2002-LSH 503094). CIBER-BBN is an initiative funded by the VI National R&D&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions, and financed by the Instituto de Salud Carlos III with assistance from the European Regional Development Fund.Esteve Moya, V.; Celda, B.; Martínez Bisbal, MC. (2012). Use of 1H and 31P HRMAS to evaluate the relationship between quantitative alterations in metabolite concentrations and tissue features in human brain tumour biopsies. 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Remodeling of the Actin/Spectrin Membrane-associated Periodic Skeleton, Growth Cone Collapse and F-Actin Decrease during Axonal Degeneration

Axonal degeneration occurs in the developing nervous system for the appropriate establishment of mature circuits, and is also a hallmark of diverse neurodegenerative diseases. Despite recent interest in the field, little is known about the changes (and possible role) of the cytoskeleton during axonal degeneration. We studied the actin cytoskeleton in an in vitro model of developmental pruning induced by trophic factor withdrawal (TFW). We found that F-actin decrease and growth cone collapse (GCC) occur early after TFW; however, treatments that prevent axonal fragmentation failed to prevent GCC, suggesting independent pathways. Using super-resolution (STED) microscopy we found that the axonal actin/spectrin membrane-associated periodic skeleton (MPS) abundance and organization drop shortly after deprivation, remaining low until fragmentation. Fragmented axons lack MPS (while maintaining microtubules) and acute pharmacological treatments that stabilize actin filaments prevent MPS loss and protect from axonal fragmentation, suggesting that MPS destruction is required for axon fragmentation to proceed.Fil: Unsain, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Bordenave, Martín Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Martinez, Gaby F.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Jalil, Sami. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Von Bilderling, Catalina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Barabas, Federico Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Masullo, Luciano Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Johnstone, Aaron D.. McGill University; CanadáFil: Barker, Philip A.. University of British Columbia; CanadáFil: Bisbal, Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; ArgentinaFil: Stefani, Fernando Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; ArgentinaFil: Caceres, Alfredo Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentin

Activation of mGluR5 Induces Rapid and Long-Lasting Protein Kinase D Phosphorylation in Hippocampal Neurons

Metabotropic glutamate receptors (mGluRs), including mGluR5, play a central role in regulating the strength and plasticity of synaptic connections in the brain. However, the signaling pathways that connect mGluRs to their downstream effectors are not yet fully understood. Here, we report that stimulation of mGluR5 in hippocampal cultures and slices results in phosphorylation of protein kinase D (PKD) at the autophosphorylation site Ser-916. This phosphorylation event occurs within 30 s of stimulation, persists for at least 24 h, and is dependent on activation of phospholipase C and protein kinase C. Our data suggest that activation of PKD may represent a novel signaling pathway linking mGluR5 to its downstream targets. These findings have important implications for the study of the molecular mechanisms underlying mGluR-dependent synaptic plasticity.Howard Hughes Medical InstituteFRAXA Research FoundationNational Institute of Mental Health (U.S.)Eunice Kennedy Shriver National Institute of Child Health and Human Development (U.S.

Performance of the ROX index to predict intubation in immunocompromised patients receiving high-flow nasal cannula for acute respiratory failure

Background Delayed intubation is associated with high mortality. There is a lack of objective criteria to decide the time of intubation. We assessed a recently described combined oxygenation index (ROX index) to predict intubation in immunocompromised patients. The study is a secondary analysis of randomized trials in immunocompromised patients, including all patients who received high-flow nasal cannula (HFNC). The first objective was to evaluate the accuracy of the ROX index to predict intubation for patients with acute respiratory failure. Results In the study, 302 patients received HFNC. Acute respiratory failure was mostly related to pneumonia (n = 150, 49.7%). Within 2 (1-3) days, 115 (38.1%) patients were intubated. The ICU mortality rate was 27.4% (n = 83). At 6 h, the ROX index was lower for patients who needed intubation compared with those who did not [4.79 (3.69-7.01) vs. 6.10 (4.48-8.68), p < 0.001]. The accuracy of the ROX index to predict intubation was poor [AUC = 0.623 (0.557-0.689)], with low performance using the threshold previously found (4.88). In multivariate analysis, a higher ROX index was still independently associated with a lower intubation rate (OR = 0.89 [0.82-0.96], p = 0.04). Conclusion A ROX index greater than 4.88 appears to have a poor ability to predict intubation in immunocompromised patients with acute respiratory failure, although it remains highly associated with the risk of intubation and may be useful to stratify such risk in future studies

Multiproject–multicenter evaluation of automatic brain tumor classification by magnetic resonance spectroscopy

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RNase L Mediated Protection from Virus Induced Demyelination

IFN-α/β plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-α/β dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-α/β pathway through RNA degradation intermediates. Infection of RNase L deficient (RL−/−) mice with a sub-lethal, demyelinating mouse hepatitis virus variant revealed that the majority of mice succumbed to infection by day 12 p.i. However, RNase L deficiency did not affect overall control of infectious virus, or diminish IFN-α/β expression in the CNS. Furthermore, increased morbidity and mortality could not be attributed to altered proinflammatory signals or composition of cells infiltrating the CNS. The unique phenotype of infected RL−/− mice was rather manifested in earlier onset and increased severity of demyelination and axonal damage in brain stem and spinal cord without evidence for enhanced neuronal infection. Increased tissue damage coincided with sustained brain stem infection, foci of microglia infection in grey matter, and increased apoptotic cells. These data demonstrate a novel protective role for RNase L in viral induced CNS encephalomyelitis, which is not reflected in overall viral control or propagation of IFN-α/β mediated signals. Protective function is rather associated with cell type specific and regional restriction of viral replication in grey matter and ameliorated neurodegeneration and demyelination