ISG15 Is Critical in the Control of Chikungunya Virus Infection Independent of UbE1L Mediated Conjugation

Chikungunya virus (CHIKV) is a re-emerging alphavirus that has caused significant disease in the Indian Ocean region since 2005. During this outbreak, in addition to fever, rash and arthritis, severe cases of CHIKV infection have been observed in infants. Challenging the notion that the innate immune response in infants is immature or defective, we demonstrate that both human infants and neonatal mice generate a robust type I interferon (IFN) response during CHIKV infection that contributes to, but is insufficient for, the complete control of infection. To characterize the mechanism by which type I IFNs control CHIKV infection, we evaluated the role of ISG15 and defined it as a central player in the host response, as neonatal mice lacking ISG15 were profoundly susceptible to CHIKV infection. Surprisingly, UbE1L−/− mice, which lack the ISG15 E1 enzyme and therefore are unable to form ISG15 conjugates, displayed no increase in lethality following CHIKV infection, thus pointing to a non-classical role for ISG15. No differences in viral loads were observed between wild-type (WT) and ISG15−/− mice, however, a dramatic increase in proinflammatory cytokines and chemokines was observed in ISG15−/− mice, suggesting that the innate immune response to CHIKV contributes to their lethality. This study provides new insight into the control of CHIKV infection, and establishes a new model for how ISG15 functions as an immunomodulatory molecule in the blunting of potentially pathologic levels of innate effector molecules during the host response to viral infection

Measuring Multi-Joint Stiffness during Single Movements: Numerical Validation of a Novel Time-Frequency Approach

This study presents and validates a Time-Frequency technique for measuring 2-dimensional multijoint arm stiffness throughout a single planar movement as well as during static posture. It is proposed as an alternative to current regressive methods which require numerous repetitions to obtain average stiffness on a small segment of the hand trajectory. The method is based on the analysis of the reassigned spectrogram of the arm's response to impulsive perturbations and can estimate arm stiffness on a trial-by-trial basis. Analytic and empirical methods are first derived and tested through modal analysis on synthetic data. The technique's accuracy and robustness are assessed by modeling the estimation of stiffness time profiles changing at different rates and affected by different noise levels. Our method obtains results comparable with two well-known regressive techniques. We also test how the technique can identify the viscoelastic component of non-linear and higher than second order systems with a non-parametrical approach. The technique proposed here is very impervious to noise and can be used easily for both postural and movement tasks. Estimations of stiffness profiles are possible with only one perturbation, making our method a useful tool for estimating limb stiffness during motor learning and adaptation tasks, and for understanding the modulation of stiffness in individuals with neurodegenerative diseases

Chronic Myeloid Leukemia Patients in Prolonged Remission following Interferon-alpha Monotherapy Have Distinct Cytokine and Oligoclonal Lymphocyte Profile

Peer reviewe

Biological therapy of cancer

Interferons and monoclonal antibodies are among the most promising biological approaches to cancer treatment which have so far been investigated. Both natural and recombinant interferon-alpha preparations have shown activity in a number of trials in hematologic malignancies, even in previously treated patients; activity in solid tumors, however, has been limited. Unconjugated monoclonal antibodies have been safely administered in several small trials and have had therapeutic value on occasion. In spite of a number of remaining problems and questions, monoclonal antibodies and their conjugates seem likely to find a number of distinct roles in cancer treatment; elimination of micrometastases and purging of bone marrow for grafting may be among these roles.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44207/1/10549_2005_Article_BF01886730.pd

Past, Present, and Future X-Ray and Gamma-Ray Missions

X- and -ray astronomy began in the early sixties of the last century with balloons flights, sounding rocket experiment and satellites. Long before space satellite detected X- and -rays emitted by cosmic sources, scientists had known that the Universe should be producing these photons. In this chapter we provided an overview of past and present missions that has made the X- and -ray astronomy an integral part of astronomical research, and prospects of future developments

Association of "Candidatus Phytoplasma australiense" with green petal and lethal yellows diseases in strawberry

The identity of phytoplasmas detected in strawberry plants with green petal (SGP) and lethal yellows (SLY) diseases was determined by RFLP analysis of the 16S rRNA gene and adjacent spacer region (SR). RFLP and sequence comparisons indicated that the phytoplasmas associated with SGP and SLY were indistinguishable and were most closely related to \u27Candidatus Phytoplasma australiense\u27, the phytoplasma associated with Australian grapevine yellows, papaya dieback and Phormium yellow leaf diseases. This taxon lies within the aster yellows strain cluster. Primers based on the phytoplasma tuf gene, which amplify only members of the AY strain cluster, amplified a DNA product from the SGP and SLY phytoplasmas. Primers deduced from the 16S rRNA/SR of P. australiense that amplify only members of this taxon amplified rDNA sequences from the SGP and SLY phytoplasmas. Primers that selectively amplify members of the faba bean phyllody (FBP) phytoplasma group, the most commonly occurring phytoplasma group in Australia, did not amplify rDNA from the SGP and SLY phytoplasmas