Toxoplasma gondii salvages sphingolipids from the host Golgi through the rerouting of selected Rab vesicles to the parasitophorous vacuole

The obligate intracellular protozoan Toxoplasma gondii actively invades mammalian cells and, upon entry, forms its own membrane-bound compartment, named the parasitophorous vacuole (PV). Within the PV, the parasite replicates and scavenges nutrients, including lipids, from host organelles. Although T. gondii can synthesize sphingolipids de novo, it also scavenges these lipids from the host Golgi. How the parasite obtains sphingolipids from the Golgi remains unclear, as the PV avoids fusion with host organelles. In this study, we explore the host Golgi–PV interaction and evaluate the importance of host-derived sphingolipids for parasite growth. We demonstrate that the PV preferentially localizes near the host Golgi early during infection and remains closely associated with this organelle throughout infection. The parasite subverts the structure of the host Golgi, resulting in its fragmentation into numerous ministacks, which surround the PV, and hijacks host Golgi–derived vesicles within the PV. These vesicles, marked with Rab14, Rab30, or Rab43, colocalize with host-derived sphingolipids in the vacuolar space. Scavenged sphingolipids contribute to parasite replication since alterations in host sphingolipid metabolism are detrimental for the parasite''s growth. Thus our results reveal that T. gondii relies on host-derived sphingolipids for its development and scavenges these lipids via Golgi-derived vesicles.     

Evaluation of new immunological targets in neuromyelitis optica

The detection of reactivity against autoantigens plays a crucial role in the diagnosis of autoimmune diseases. However, only a few autoantibodies are known in each disease, and their precise targets are often not precisely defined. In neuromyelitis optica (NMO), an autoimmune disease of the central nervous system, anti‐aquaporin 4 antibodies are currently the only available immunological markers, although they are not detected in 10–50% of patients. Using enzyme‐linked immunosorbent assays, we evaluated the reactivity against 19 structurally defined peptides in 26 NMO sera compared with 21 healthy subjects. We observed increased levels of IgG against myelin basic protein sequence MBP(156–175), pyruvate dehydrogenase sequence PDH(167–186) and CSF114(Glc), the last of these having a possible correlation with onset of inflammatory relapse. These preliminary results may suggest that the aquaporin 4 is not the unique target in NMO and that the study of reactivity against these peptides would be helpful for the diagnosis and follow‐up of the disease. Complementary studies are however warranted to confirm these results. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.     

Genomic alterations in human umbilical cord–derived mesenchymal stromal cells call for stringent quality control before any possible therapeutic approach

Background aimsThe umbilical cord (UC) is a promising source of mesenchymal stromal cells (MSCs). UC-MSCs display very similar in vitro characteristics to bone marrow–MSCs and could represent a valuable alternative for cell-based therapies. However, it is still unclear whether UC-MSCs are prone or not to the acquisition of genomic imbalances during in vitro expansion.MethodsWith the use of array-comparative genomic hybridization, we compared copy number variations of early (P2–P3) and late (>P5) passages of in vitro–expanded UC-MSCs.ResultsIn two of 11 long-term UC-MSCs cultures, we observed the appearance of clones carrying genomic imbalances, which generated genetic mosaicism at intermediate passages. Although still able to reach the senescence phase, the cells carrying the genomic imbalance acquired a proliferative advantage, as demonstrated by the increase in frequency during long-term culture.ConclusionsAltogether, our results suggest that UC-MSC–based clinical protocols should be designed with caution; their clinical use should be preceded by array-comparative genomic hybridization screening for the acquisition of genomic imbalances during in vitro expansion.     

Myofibroblast expression in airways and alveoli is affected by smoking and COPD

Background

Chronic obstructive pulmonary disease (COPD) is characterized by structural changes in alveoli and airways. Our aim was to analyse the numbers of alpha-smooth muscle actin (α-SMA) positive cells, as a marker of myofibroblasts, in different lung compartments in non-smokers and smokers with normal lung function or COPD.

Methods

α-SMA, tenascin-C (Tn-C) and EDA-fibronectin in alveolar level and airways were assayed by immunohistochemistry and quantified by image analysis. Immunohistochemical findings were correlated with clinical data. α-SMA protein was also analysed by Western blotting from fibroblastic cells cultured from peripheral lung of non-smokers, smokers without COPD and smokers with COPD.

Results

In many cases, the endings of the detached alveolar walls were widened, the structures of which were named as widened alveolar tips. Widened alveolar tips contained α-SMA positive cells, which were obviously myofibroblasts. There were less alveolar tips containing positive cells for α-SMA in alveoli and α-SMA positive cells in bronchioles in smokers and in COPD compared to non-smokers. The quantity of α-SMA positive cells was increased in bronchi in COPD. Tn-C was elevated in bronchi in COPD and smokers’ lung. The α-SMA protein level was 1.43-fold higher in stromal cells cultured from non-smokers than in those of smokers.

Conclusions

Myofibroblasts are localized variably in normal and diseased lung. This indicates that they have roles in both regeneration of lung and pathogenesis of COPD. The widened alveolar tips, these newly characterized histological structures, seemed to be the source of myofibroblasts at the alveolar level.     

Globalization of biotechnology: The agglomeration of dispersed knowledge and information and its implications for the political economy of technology in developing countries

This study examines a contradictory development in the era of globalization wherein country-specific economic and socio-political institutional environment limits the global flow of technological knowledge and information, particularly in the biotechnology sector. International collaborations for developing new biotechnologies has increased significantly in recent years, but these have virtually bypassed firms in developing countries. The international flow of technologies tends to agglomerate in developed economies particularly in the US, where an appropriate mix of economic choices, social regulation and state action fostered institutional environments that facilitated the development and commercialization of biotechnologies. Moreover, with the heightening competition in the global economy, state and firms of developed economies have evolved into a relationship of close partnership. This shows that, far from being irrelevant, the state remains a political entity that structures the innovation system in order to promote the well-being of its firms. This calls for a re-thinking of the role of the state in technological and economic development, particularly among the developing economies.     

Pioneer settlement of the cold-water coral Desmophyllum dianthus (Esper, 1794) on plastic

Coral Reefs - Larval settlement is a critical step for sessile benthic species such as corals, whose ability to thrive on diverse natural and anthropogenic substrates may lead to a competitive...     

Virulence Factors and Antifungal Susceptibility in Candida Species Isolated from Dermatomycosis Patients

Mycopathologia - Dermatomycoses caused by Candida spp. are increasingly common, however there are few reports in the literature regarding their epidemiology, pathogenesis and antifungal...     

Prenatal and pubertal exposure to 17α-ethinylestradiol cause morphological changes in the prostate of old gerbils

This study evaluated such as exposure to ethinylestradiol during the prenatal (18th–22nd day) and pubertal (42nd–49th day) periods acts on the male ventral prostate and female prostate of 12-month old gerbils. We performed the analysis to serum hormone levels for estradiol and testosterone. The prostates were submitted to morphometric and immunohistochemical analyses. Exposure to ethinylestradiol during these developmental periods decreased the testosterone serum levels in males and increased the estradiol serum levels in females. Morphologically, prostate intraepithelial neoplasia and disorders in the arrangement of the fibrous components were observed in the prostate glands of both sexes of gerbil exposed to ethinylestradiol during development periods. In the male prostate, the ethinylestradiol promoted decreased in the frequency of positive epithelial cell for androgen receptor (AR) and increased the frequency of positive stromal cell for estrogen receptor α. However, in the female prostate, this synthetic estrogen caused AR upregulation and increased cell proliferation. This study shows that the exposure to ethinylestradiol during development phases alters the morphology and the hormonal signaling in the male and female prostates of old gerbils, confirming the action of ethinylestradiol as endocrine disruptor.