Pericyte degeneration causes white matter dysfunction in the mouse central nervous system

Diffuse white-matter disease associated with small-vessel disease and dementia is prevalent in the elderly. The biological mechanisms, however, remain elusive. Using pericyte-deficient mice, magnetic resonance imaging, viral-based tract-tracing, and behavior and tissue analysis, we found that pericyte degeneration disrupted white-matter microcirculation, resulting in an accumulation of toxic blood-derived fibrin(ogen) deposits and blood-flow reductions, which triggered a loss of myelin, axons and oligodendrocytes. This disrupted brain circuits, leading to white-matter functional deficits before neuronal loss occurs. Fibrinogen and fibrin fibrils initiated autophagy-dependent cell death in oligodendrocyte and pericyte cultures, whereas pharmacological and genetic manipulations of systemic fibrinogen levels in pericyte-deficient, but not control mice, influenced the degree of white-matter fibrin(ogen) deposition, pericyte degeneration, vascular pathology and white-matter changes. Thus, our data indicate that pericytes control white-matter structure and function, which has implications for the pathogenesis and treatment of human white-matter disease associated with small-vessel disease

Inflammatory Gene Regulatory Networks in Amnion Cells Following Cytokine Stimulation: Translational Systems Approach to Modeling Human Parturition

A majority of the studies examining the molecular regulation of human labor have been conducted using single gene approaches. While the technology to produce multi-dimensional datasets is readily available, the means for facile analysis of such data are limited. The objective of this study was to develop a systems approach to infer regulatory mechanisms governing global gene expression in cytokine-challenged cells in vitro, and to apply these methods to predict gene regulatory networks (GRNs) in intrauterine tissues during term parturition. To this end, microarray analysis was applied to human amnion mesenchymal cells (AMCs) stimulated with interleukin-1β, and differentially expressed transcripts were subjected to hierarchical clustering, temporal expression profiling, and motif enrichment analysis, from which a GRN was constructed. These methods were then applied to fetal membrane specimens collected in the absence or presence of spontaneous term labor. Analysis of cytokine-responsive genes in AMCs revealed a sterile immune response signature, with promoters enriched in response elements for several inflammation-associated transcription factors. In comparison to the fetal membrane dataset, there were 34 genes commonly upregulated, many of which were part of an acute inflammation gene expression signature. Binding motifs for nuclear factor-κB were prominent in the gene interaction and regulatory networks for both datasets; however, we found little evidence to support the utilization of pathogen-associated molecular pattern (PAMP) signaling. The tissue specimens were also enriched for transcripts governed by hypoxia-inducible factor. The approach presented here provides an uncomplicated means to infer global relationships among gene clusters involved in cellular responses to labor-associated signals

Study on the digenetic trematode Schistosomatium douthitti.

http://deepblue.lib.umich.edu/bitstream/2027.42/52248/1/679.pdfDescription of 679.pdf : Access restricted to on-site users at the U-M Biological Station

Observations on cercaria of Schistosomatium douthitti.

http://deepblue.lib.umich.edu/bitstream/2027.42/52249/1/680.pdfDescription of 680.pdf : Access restricted to on-site users at the U-M Biological Station

Difficulties in organizing first indoor spray programme against malaria in Angola under the President's Malaria Initiative

PROBLEM: Successful attempts to control malaria require understanding of its complex transmission patterns. Unfortunately malaria transmission in Africa is often assessed using routine administrative reports from local health units, which are plagued by sporadic reporting failures. In addition, the lack of microscopic analyses of blood slides in these units introduces the effects of many confounding diseases. APPROACH: The danger of using administrative reports was illustrated in Angola, the first country in which malaria control was attempted under the President's Malaria Initiative, a development programme of the Government of the United States of America. LOCAL SETTING: Each local health unit submitted monthly reports indicating the number of suspected malaria cases to their municipality. The identification of the disease was based on clinical diagnoses, without microscopic examination of blood slides. The municipal and provincial reports were then passed on to the national headquarters, with sporadic reporting lapses at all levels. RELEVANT CHANGES: After the control effort was completed, the defective municipal reports were corrected by summarizing only the data from those health units which had submitted reports for every month during the evaluation period. LESSONS LEARNED: The corrected data, supplemented by additional observations on rainfall and mosquito habitats, indicated that there had probably been no malaria transmission before starting the control operations. Thus the expensive malaria control effort had been wasted. It is unfortunate that WHO is also trying to plan and evaluate its malaria control efforts based on these same kinds of inadequate administrative reports

Título en español.

Biological control methods for schistosomiasis in man and fascioliasis in cattle include the use of Marisa cornuarietis, a predatory snail. To insure that this snail does not transmit the trematode parasites, laboratory exposures were made under favorable conditions. It was found that Marisa cornuarietis, as well as other potential biological control snails, did not transmit either of the two parasites.Resumen en español