Texas Lifestyle Limits Transmission of Dengue Virus

Urban dengue is common in most countries of the Americas, but has been rare in the United States for more than half a century. In 1999 we investigated an outbreak of the disease that affected Nuevo Laredo, Tamaulipas, Mexico, and Laredo, Texas, United States, contiguous cities that straddle the international border. The incidence of recent cases, indicated by immunoglobulin M antibody serosurvey, was higher in Nuevo Laredo, although the vector, Aedes aegypti, was more abundant in Laredo. Environmental factors that affect contact with mosquitoes, such as air-conditioning and human behavior, appear to account for this paradox. We conclude that the low prevalence of dengue in the United States is primarily due to economic, rather than climatic, factors

The U.S.-Mexico Border Infectious Disease Surveillance Project: Establishing Binational Border Surveillance

In 1997, the Centers for Disease Control and Prevention, the Mexican Secretariat of Health, and border health officials began the development of the Border Infectious Disease Surveillance (BIDS) project, a surveillance system for infectious diseases along the U.S.-Mexico border. During a 3-year period, a binational team implemented an active, sentinel surveillance system for hepatitis and febrile exanthems at 13 clinical sites. The network developed surveillance protocols, trained nine surveillance coordinators, established serologic testing at four Mexican border laboratories, and created agreements for data sharing and notification of selected diseases and outbreaks. BIDS facilitated investigations of dengue fever in Texas-Tamaulipas and measles in California–Baja California. BIDS demonstrates that a binational effort with local, state, and federal participation can create a regional surveillance system that crosses an international border. Reducing administrative, infrastructure, and political barriers to cross-border public health collaboration will enhance the effectiveness of disease prevention projects such as BIDS

Current European Labyrinthula zosterae Are Not Virulent and Modulate Seagrass (Zostera marina) Defense Gene Expression

Pro- and eukaryotic microbes associated with multi-cellular organisms are receiving increasing attention as a driving factor in ecosystems. Endophytes in plants can change host performance by altering nutrient uptake, secondary metabolite production or defense mechanisms. Recent studies detected widespread prevalence of Labyrinthula zosterae in European Zostera marina meadows, a protist that allegedly caused a massive amphi-Atlantic seagrass die-off event in the 1930's, while showing only limited virulence today. As a limiting factor for pathogenicity, we investigated genotype×genotype interactions of host and pathogen from different regions (10–100 km-scale) through reciprocal infection. Although the endophyte rapidly infected Z. marina, we found little evidence that Z. marina was negatively impacted by L. zosterae. Instead Z. marina showed enhanced leaf growth and kept endophyte abundance low. Moreover, we found almost no interaction of protist×eelgrass-origin on different parameters of L. zosterae virulence/Z. marina performance, and also no increase in mortality after experimental infection. In a target gene approach, we identified a significant down-regulation in the expression of 6/11 genes from the defense cascade of Z. marina after real-time quantitative PCR, revealing strong immune modulation of the host's defense by a potential parasite for the first time in a marine plant. Nevertheless, one gene involved in phenol synthesis was strongly up-regulated, indicating that Z. marina plants were probably able to control the level of infection. There was no change in expression in a general stress indicator gene (HSP70). Mean L. zosterae abundances decreased below 10% after 16 days of experimental runtime. We conclude that under non-stress conditions L. zosterae infection in the study region is not associated with substantial virulence

Tubulin Tyrosination Is Required for the Proper Organization and Pathfinding of the Growth Cone

International audienceBACKGROUND: During development, neuronal growth cones integrate diffusible and contact guidance cues that are conveyed to both actin and microtubule (MT) cytoskeletons and ensure axon outgrowth and pathfinding. Although several post-translational modifications of tubulin have been identified and despite their strong conservation among species, their physiological roles during development, especially in the nervous sytem, are still poorly understood. METHODOLOGY/FINDINGS: Here, we have dissected the role of a post-translational modification of the last amino acid of the alpha-tubulin on axonal growth by analyzing the phenotype of precerebellar neurons in Tubulin tyrosin ligase knock-out mice (TTL(-/-)) through in vivo, ex vivo and in vitro analyses. TTL(-/-) neurons are devoid of tyrosinated tubulin. Their pathway shows defects in vivo, ex vivo, in hindbrains open-book preparations or in vitro, in a collagen matrix. Their axons still orient toward tropic cues, but they emit supernumerary branches and their growth cones are enlarged and exhibit an emission of mis-oriented filopodia. Further analysis of the TTL(-/-) growth cone intracellular organization also reveals that the respective localization of actin and MT filaments is disturbed, with a decrease in the distal accumulation of Myosin IIB, as well as a concomitant Rac1 over-activation in the hindbrain. Pharmacological inhibition of Rac1 over-activation in TTL(-/-) neurons can rescue Myosin IIB localization. CONCLUSIONS/SIGNIFICANCE: In the growth cone, we propose that tubulin tyrosination takes part in the relative arrangement of actin and MT cytoskeletons, in the regulation of small GTPases activity, and consequently, in the proper morphogenesis, organization and pathfinding of the growth cone during development

Long-Term Programming of Antigen-Specific Immunity from Gene Expression Signatures in the PBMC of Rhesus Macaques Immunized with an SIV DNA Vaccine

While HIV-1-specific cellular immunity is thought to be critical for the suppression of viral replication, the correlates of protection have not yet been determined. Rhesus macaques (RM) are an important animal model for the study and development of vaccines against HIV/AIDS. Our laboratory has helped to develop and study DNA-based vaccines in which recent technological advances, including genetic optimization and in vivo electroporation (EP), have helped to dramatically boost their immunogenicity. In this study, RMs were immunized with a DNA vaccine including individual plasmids encoding SIV gag, env, and pol alone, or in combination with a molecular adjuvant, plasmid DNA expressing the chemokine ligand 5 (RANTES), followed by EP. Along with standard immunological assays, flow-based activation analysis without ex vivo restimulation and high-throughput gene expression analysis was performed. Strong cellular immunity was induced by vaccination which was supported by all assays including PBMC microarray analysis that identified the up-regulation of 563 gene sequences including those involved in interferon signaling. Furthermore, 699 gene sequences were differentially regulated in these groups at peak viremia following SIVmac251 challenge. We observed that the RANTES-adjuvanted animals were significantly better at suppressing viral replication during chronic infection and exhibited a distinct pattern of gene expression which included immune cell-trafficking and cell cycle genes. Furthermore, a greater percentage of vaccine-induced central memory CD8+ T-cells capable of an activated phenotype were detected in these animals as measured by activation analysis. Thus, co-immunization with the RANTES molecular adjuvant followed by EP led to the generation of cellular immunity that was transcriptionally distinct and had a greater protective efficacy than its DNA alone counterpart. Furthermore, activation analysis and high-throughput gene expression data may provide better insight into mechanisms of viral control than may be observed using standard immunological assays

Molecular Motor Proteins and Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor neurons in the brain, brainstem and spinal cord, which is characterized by motor dysfunction, muscle dystrophy and progressive paralysis. Both inherited and sporadic forms of ALS share common pathological features, however, the initial trigger of neurodegeneration remains unknown. Motor neurons are uniquely targeted by ubiquitously expressed proteins in ALS but the reason for this selectively vulnerability is unclear. However motor neurons have unique characteristics such as very long axons, large cell bodies and high energetic metabolism, therefore placing high demands on cellular transport processes. Defects in cellular trafficking are now widely reported in ALS, including dysfunction to the molecular motors dynein and kinesin. Abnormalities to dynein in particular are linked to ALS, and defects in dynein-mediated axonal transport processes have been reported as one of the earliest pathologies in transgenic SOD1 mice. Furthermore, dynein is very highly expressed in neurons and neurons are particularly sensitive to dynein dysfunction. Hence, unravelling cellular transport processes mediated by molecular motor proteins may help shed light on motor neuron loss in ALS

Observing pain management practice on a medical unit following changes arising from an action research study

Aim.  To describe pain assessment practice within a medical unit, to identify factors that may affect the assessment of pain and evaluate changes in practice. Background.  Pain is a problem for patients in all areas of a hospital, but its assessment and management on medical units had not been investigated. An initial assessment of practice found that pain was not consistently assessed and managed on the unit. A variety of activities have been employed during an action research study to change pain management practice. Method.  Naturalistic unstructured participant observation of nurses and structured patient interviews were conducted. Results.  The need to communicate with many people led to interruptions, multi-tasking and practical problems were observed which appeared to affect the provision of nursing care, in particular, the administration of medications. These factors also prevented a comprehensive assessment of pain, although the assessment of pain intensity appeared to have increased. Discussion.  The constant activity and interruptions observed may make it difficult for patients to discuss their experience of pain in detail. These accepted, every day and taken-for-granted aspects of nursing observed appeared to reduce opportunities for comprehensive pain assessment. Conclusion.  Pain assessment is one of a number of nursing activities, obtaining a pain score appears to have become routine practice. Nursing takes place in a complex environment, which may disrupt the provision of nursing care and impede communication. Relevance to practice.  To increase nurses awareness of the complexity of every day practice, the numerous tasks required, interruptions to the provision of care and the resultant effect on pain assessment and management. They need to then identify and reflect on these factors prior to attempting to change their practice