Single Collateral Reconstructions Reveal Distinct Phases of Corticospinal Remodeling after Spinal Cord Injury

Injuries to the spinal cord often result in severe functional deficits that, in case of incomplete injuries, can be partially compensated by axonal remodeling. The corticospinal tract (CST), for example, responds to a thoracic transection with the formation of an intraspinal detour circuit. The key step for the formation of the detour circuit is the sprouting of new CST collaterals in the cervical spinal cord that contact local interneurons. How individual collaterals are formed and refined over time is incompletely understood

Resistance of Asian Cryptococcus neoformans Serotype A Is Confined to Few Microsatellite Genotypes

Contains fulltext : 109375.pdf (publisher's version ) (Open Access)BACKGROUND: Cryptococcus neoformans is a pathogenic yeast that causes cryptococcosis, a life threatening disease. The prevalence of cryptococcosis in Asia has been rising after the onset of the AIDS epidemic and estimates indicate more than 120 cases per 1,000 HIV-infected individuals per year. Almost all cryptococcal disease cases in both immunocompromised and immunocompetent patients in Asia are caused by C. neoformans var. grubii. Epidemiological studies on C. neoformans in pan-Asia have not been reported. The present work studies the genetic diversity of the fungus by microsatellite typing and susceptibility analysis of approximately 500 isolates from seven Asian countries. METHODOLOGY/PRINCIPAL FINDINGS: Genetic diversity of Asian isolates of C. neoformans was determined using microsatellite analysis with nine microsatellite markers. The analysis revealed eight microsatellite complexes (MCs) which showed different distributions among geographically defined populations. A correlation between MCs and HIV-status was observed. Microsatellite complex 2 was mainly associated with isolates from HIV-negative patients, whereas MC8 was associated with those from HIV-positive patients. Most isolates were susceptible to amphotericin B, itraconazole, voriconazole, posaconazole, and isavuconazole, but 17 (3.4%) and 10 (2%) were found to be resistant to 5-flucytosine and fluconazole, respectively. Importantly, five Indonesian isolates (approximately 12.5% from all Indonesian isolates investigated and 1% from the total studied isolates) were resistant to both antifungals. The majority of 5-flucytosine resistant isolates belonged to MC17. CONCLUSIONS: The findings showed a different distribution of genotypes of C. neoformans var. grubii isolates from various countries in Asia, as well as a correlation of the microsatellite genotypes with the original source of the strains and resistance to 5-flucytosine

Macrophage secretory phospholipase A2 group X enhances anti-inflammatory responses, promotes lipid accumulation, and contributes to aberrant lung pathology.

Secreted phospholipase A2 group X (sPLA(2)-X) is one of the most potent enzymes of the phospholipase A(2) lipolytic enzyme superfamily. Its high catalytic activity toward phosphatidylcholine (PC), the major phospholipid of cell membranes and low-density lipoproteins (LDL), has implicated sPLA(2)-X in chronic inflammatory conditions such as atherogenesis. We studied the role of sPLA(2)-X enzyme activity in vitro and in vivo, by generating sPLA(2)-X-overexpressing macrophages and transgenic macrophage-specific sPLA(2)-X mice. Our results show that sPLA(2)-X expression inhibits macrophage activation and inflammatory responses upon stimulation, characterized by reduced cell adhesion and nitric oxide production, a decrease in tumor necrosis factor (TNF), and an increase in interleukin (IL)-10. These effects were mediated by an increase in IL-6, and enhanced production of prostaglandin E(2) (PGE(2)) and 15-deoxy-Delta12,14-prostaglandin J(2) (PGJ(2)). Moreover, we found that overexpression of active sPLA(2)-X in macrophages strongly increases foam cell formation upon incubation with native LDL but also oxidized LDL (oxLDL), which is mediated by enhanced expression of scavenger receptor CD36. Transgenic sPLA(2)-X mice died neonatally because of severe lung pathology characterized by interstitial pneumonia with massive granulocyte and surfactant-laden macrophage infiltration. We conclude that overexpression of the active sPLA(2)-X enzyme results in enhanced foam cell formation but reduced activation and inflammatory responses in macrophages in vitro. Interestingly, enhanced sPLA(2)-X activity in macrophages in vivo leads to fatal pulmonary defects, suggesting a crucial role for sPLA(2)-X in inflammatory lung disease

Myeloid I kappa B alpha Deficiency Promotes Atherogenesis by Enhancing Leukocyte Recruitment to the Plaques

Activation of the transcription factor NF-kappa B appears to be involved in different stages of atherogenesis. In this paper we investigate the role of NF-kappa B inhibitor I kappa B alpha in atherosclerosis. Myeloid-specific deletion of I kappa B alpha results in larger and more advanced lesions in LDL-R-deficient mice without affecting the compositional phenotype of the plaques or systemic inflammatory markers in the plasma. We show that I kappa B alpha-deleted macrophages display enhanced adhesion to an in vitro endothelial cell layer, coinciding with an increased expression of the chemokine CCL5. Also, in vivo we found that I kappa B alpha(del) mice had more leukocytes adhering to the luminal side of the endothelial cell layers that cover the atherosclerotic plaques. Moreover, we introduce ER-MP58 in this paper as a new immunohistochemical tool for quantifying newly recruited myeloid cells in the atherosclerotic lesion. This staining confirms that in I kappa B alpha(del) mice more leukocytes are attracted to the plaques. In conclusion, we show that I kappa B alpha deletion in myeloid cells promotes atherogenesis, probably through an induced leukocyte recruitment to plaques

Assessment of the Oral Bioavailability of Organic Contaminants in Humans

Bioavailability estimates the actual internal uptake or absorption of contaminants that enter the body (internal dose) and helps in providing a more accurate estimation of the human risks than the usage of total concentration. This is important for exposure assessment for children in relation to their hand-to-mouth activities. For example significant reductions of the bioavailability of long-term contaminated soils have been demonstrated using various animal models. The measurement for bioavailability involves various uncertainties for organic contaminants. It is crucial to determine the parameters that influence the results of bioavailability. This chapter provides a summary of the current state of knowledge for the determination of bioavailability for a range of organic contaminants. The information provided will be useful in facilitating further research efforts for the investigation of bioavailability of contaminants in conducting exposure assessments