Congenital Viral Infections of the Brain: Lessons Learned from Lymphocytic Choriomeningitis Virus in the Neonatal Rat

The fetal brain is highly vulnerable to teratogens, including many infectious agents. As a consequence of prenatal infection, many children suffer severe and permanent brain injury and dysfunction. Because most animal models of congenital brain infection do not strongly mirror human disease, the models are highly limited in their abilities to shed light on the pathogenesis of these diseases. The animal model for congenital lymphocytic choriomeningitis virus (LCMV) infection, however, does not suffer from this limitation. LCMV is a well-known human pathogen. When the infection occurs during pregnancy, the virus can infect the fetus, and the developing brain is particularly vulnerable. Children with congenital LCMV infection often have substantial neurological deficits. The neonatal rat inoculated with LCMV is a superb model system of human congenital LCMV infection. Virtually all of the neuropathologic changes observed in humans congenitally infected with LCMV, including microencephaly, encephalomalacia, chorioretinitis, porencephalic cysts, neuronal migration disturbances, periventricular infection, and cerebellar hypoplasia, are reproduced in the rat model. Within the developing rat brain, LCMV selectively targets mitotically active neuronal precursors. Thus, the targets of infection and sites of pathology depend on host age at the time of infection. The rat model has further shown that the pathogenic changes induced by LCMV infection are both virus-mediated and immune-mediated. Furthermore, different brain regions simultaneously infected with LCMV can undergo widely different pathologic changes, reflecting different brain region–virus–immune system interactions. Because the neonatal rat inoculated with LCMV so faithfully reproduces the diverse neuropathology observed in the human counterpart, the rat model system is a highly valuable tool for the study of congenital LCMV infection and of all prenatal brain infections In addition, because LCMV induces delayed-onset neuronal loss after the virus has been cleared, the neonatal rat infected with LCMV may be an excellent model system to study neurodegenerative or psychiatric diseases whose etiologies are hypothesized to be virus-induced, such as autism, schizophrenia, and temporal lobe epilepsy

Pattern languages in HCI: A critical review

This article presents a critical review of patterns and pattern languages in human-computer interaction (HCI). In recent years, patterns and pattern languages have received considerable attention in HCI for their potential as a means for developing and communicating information and knowledge to support good design. This review examines the background to patterns and pattern languages in HCI, and seeks to locate pattern languages in relation to other approaches to interaction design. The review explores four key issues: What is a pattern? What is a pattern language? How are patterns and pattern languages used? and How are values reflected in the pattern-based approach to design? Following on from the review, a future research agenda is proposed for patterns and pattern languages in HCI

Identification of possible source markers in marine dissolved organic matter using ultrahigh resolution mass spectrometry

Author Posting. © Elsevier B.V., 2009. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Geochimica et Cosmochimica Acta 73 (2009): 4384-4399, doi:10.1016/j.gca.2009.04.033.Marine dissolved organic matter (DOM) is one of the most heterogeneous and largest pools of reactive carbon on earth, rivaling in mass the carbon in atmospheric carbon dioxide. Nevertheless, the molecular-level composition of marine DOM has eluded detailed description, impeding inquiry into the specific mechanisms that add or remove compounds from the DOM pool. Here we describe the molecular-level composition of C18-extracted DOM along an east-west transect of the North Atlantic Ocean. We examine the changes in DOM composition along this transect with ultrahigh resolution mass spectrometry and multivariate statistics. We use indicator species analysis (ISA) to identify possible source markers for photochemical degradation and heterotrophic bacterial metabolism. The inclusion of ISA in statistical evaluation of DOM mass spectral data allows investigators to determine the m/z values associated with significant changes in DOM composition. With this technique, we observe indicator m/z values in estuarine water that may represent components of terrestrially-derived chromophoric DOM subject to photo-chemical degradation. We also observe a unique set of m/z values in surface seawater and show that many of these are present in pure cultures of the marine α-proteobacterium Candidatus Pelagibacter ubique when grown in natural seawater. These findings indicate that a complex balance of abiotic and biotic processes controls the molecular composition of marine DOM to produce signatures that are characteristic of different environments.The authors gratefully acknowledge the funding sources for this work: the National Science Foundation (OCE-0443217 (EBK, NVB, RDV), CAREER-OCE- 0529101(EBK)), the Gordon and Betty Moore Foundation Marine Microbiology Initiative (SJG) and WHOI startup funds (EBK)

Predicting total reaction cross sections for nucleon-nucleus scattering

Nucleon total reaction and neutron total cross sections to 300 MeV for 12C and 208Pb, and for 65 MeV spanning the mass range, are predicted using coordinate space optical potentials formed by full folding of effective nucleon-nucleon interactions with realistic nuclear ground state densities. Good to excellent agreement is found with existing data.Comment: 10 pages, 4 figure

Cross-feeding between intestinal pathobionts promotes their overgrowth during undernutrition

Child undernutrition is a global health issue associated with a high burden of infectious disease. Undernourished children display an overabundance of intestinal pathogens and pathobionts, and these bacteria induce enteric dysfunction in undernourished mice; however, the cause of their overgrowth remains poorly defined. Here, we show that disease-inducing human isolates of Enterobacteriaceae and Bacteroidales spp. are capable of multi-species symbiotic cross-feeding, resulting in synergistic growth of a mixed community in vitro. Growth synergy occurs uniquely under malnourished conditions limited in protein and iron: in this context, Bacteroidales spp. liberate diet- and mucin-derived sugars and Enterobacteriaceae spp. enhance the bioavailability of iron. Analysis of human microbiota datasets reveals that Bacteroidaceae and Enterobacteriaceae are strongly correlated in undernourished children, but not in adequately nourished children, consistent with a diet-dependent growth synergy in the human gut. Together these data suggest that dietary cross-feeding fuels the overgrowth of pathobionts in undernutrition

High-Precision Measurement of the 19Ne Half-Life and Implications for Right-Handed Weak Currents

We report a precise determination of the 19Ne half-life to be $T_{1/2} = 17.262 \pm 0.007$ s. This result disagrees with the most recent precision measurements and is important for placing bounds on predicted right-handed interactions that are absent in the current Standard Model. We are able to identify and disentangle two competing systematic effects that influence the accuracy of such measurements. Our findings prompt a reassessment of results from previous high-precision lifetime measurements that used similar equipment and methods.Comment: 5 pages and 5 figures. Paper accepted for publication in Phys. Rev. Let

Comparison of Transfer-to-Continuum and Eikonal Models of Projectile Fragmentation Reactions

Spectroscopic properties of nuclei are accessible with projectile fragmentation reactions, but approximations made in the reaction theory can limit the accuracy of the determinations. We examine here two models that have rather different approximations for the nucleon wave function, the target interaction, and the treatment of the finite duration of the reaction. The nucleon-target interaction is treated differently in the eikonal and the transfer-to-continuum model, but the differences are more significant for light targets. We propose a new parameterization with that in mind. We also propose a new formula to calculate the amplitude that combines the better treatment of the wave function in the eikonal model with the better treatment of the target interaction in the transfer-to-continuum model.Comment: 21 pages, latex file including 3 tables. 5 figures. Submitted to Phys. Rev.

Avoiding a dystopian future for children's play

Describes the conflict between children's freedom to play and the quest for safety and makes recommendations for the future