Aerobic nonylphenol degradation and nitro-nonylphenol formation by microbial cultures from sediments

Nonylphenol (NP) is an estrogenic pollutant which is widely present in the aquatic environment. Biodegradation of NP can reduce the toxicological risk. In this study, aerobic biodegradation of NP in river sediment was investigated. The sediment used for the microcosm experiments was aged polluted with NP. The biodegradation of NP in the sediment occurred within 8 days with a lag phase of 2 days at 30°C. During the biodegradation, nitro-nonylphenol metabolites were formed, which were further degraded to unknown compounds. The attached nitro-group originated from the ammonium in the medium. Five subsequent transfers were performed from original sediment and yielded a final stable population. In this NP-degrading culture, the microorganisms possibly involved in the biotransformation of NP to nitro-nonylphenol were related to ammonium-oxidizing bacteria. Besides the degradation of NP via nitro-nonylphenol, bacteria related to phenol-degrading species, which degrade phenol via ring cleavage, are abundantly present

Ifosfamide/etoposide alternating with high-dose methotrexate: evaluation of a chemotherapy regimen for poor-risk osteosarcoma

Fifteen patients with relapsed osteosarcoma were treated with an intensive combination chemotherapy schedule. Ifosfamide 2.5 g m−2 daily and etoposide 150 mg m−2 daily coincidentally for 3 days and high-dose methotrexate 8 g m−2 (with folinic acid rescue) on days 10–14 in a planned 21-day cycle. Feasibility, toxicity and response to this alternative combination for the treatment of relapsed osteosarcoma was assessed. There were 98 evaluable cycles for toxicity and tolerability. The majority of cycles were well tolerated. Haematological toxicity of grade 3/4 (common toxicity criteria) was seen in all courses. Renal tubular loss of electrolytes, particularly magnesium, occurred in 71% of cycles. Thirteen per cent of cycles were repeated within 21 days and 61% within 28 days. In the thirteen patients evaluable for response, a partial response rate of 31% was seen after two cycles. However, patients with stable disease continued on therapy, and an overall consequent response rate of 62% was observed. Four patients were alive with no evidence of disease at 8–74 months. Three are alive with disease (at 8–19 months). There were six deaths, all disease related. This regimen exhibits an encouraging response rate in a group of children with poor prognosis disease, with a tolerable toxicity profile. © 1999 Cancer Research Campaig

Nestin-GFP Transgene Reveals Neural Precursor Cells in Adult Skeletal Muscle

Background: Therapy for neural lesions or degenerative diseases relies mainly on finding transplantable active precursor cells. Identifying them in peripheral tissues accessible for biopsy, outside the central nervous system, would circumvent the serious immunological and ethical concerns impeding cell therapy. Methodology/Principal Findings: In this study, we isolated neural progenitor cells in cultured adult skeletal muscle from transgenic mice in which nestin regulatory elements control GFP expression. These cells also expressed the early neural marker Tuj1 and light and heavy neurofilament but not S100b, indicating that they express typical neural but not Schwann cell markers. GFP+/Tuj1+ cells were also negative for the endothelial and pericyte markers CD31 and a-smooth muscle actin, respectively. We established their a) functional response to glutamate in patch-clamp recordings; b) interstitial mesenchymal origin; c) replicative capacity; and d) the environment necessary for their survival after fluorescenceactivated cell sorting. Conclusions/Significance: We propose that the decline in nestin-GFP expression in muscle progenitor cells and its persistence in neural precursor cells in muscle cultures provide an invaluable tool for isolating a population of predifferentiated neural cells with therapeutic potential

Spatial Modulation of Primate Inferotemporal Responses by Eye Position

Background: A key aspect of representations for object recognition and scene analysis in the ventral visual stream is the spatial frame of reference, be it a viewer-centered, object-centered, or scene-based coordinate system. Coordinate transforms from retinocentric space to other reference frames involve combining neural visual responses with extraretinal postural information. Methodology/Principal Findings: We examined whether such spatial information is available to anterior inferotemporal (AIT) neurons in the macaque monkey by measuring the effect of eye position on responses to a set of simple 2D shapes. We report, for the first time, a significant eye position effect in over 40 % of recorded neurons with small gaze angle shifts from central fixation. Although eye position modulates responses, it does not change shape selectivity. Conclusions/Significance: These data demonstrate that spatial information is available in AIT for the representation of objects and scenes within a non-retinocentric frame of reference. More generally, the availability of spatial information in AIT calls into questions the classic dichotomy in visual processing that associates object shape processing with ventra

Highly Pathogenic H5N1 Influenza Viruses Carry Virulence Determinants beyond the Polybasic Hemagglutinin Cleavage Site

Highly pathogenic avian influenza viruses (HPAIV) originate from avirulent precursors but differ from all other influenza viruses by the presence of a polybasic cleavage site in their hemagglutinins (HA) of subtype H5 or H7. In this study, we investigated the ability of a low-pathogenic avian H5N1 strain to transform into an HPAIV. Using reverse genetics, we replaced the monobasic HA cleavage site of the low-pathogenic strain A/Teal/Germany/Wv632/2005 (H5N1) (TG05) by a polybasic motif from an HPAIV (TG05poly). To elucidate the virulence potential of all viral genes of HPAIV, we generated two reassortants carrying the HA from the HPAIV A/Swan/Germany/R65/06 (H5N1) (R65) plus the remaining genes from TG05 (TG05-HAR65) or in reversed composition the mutated TG05 HA plus the R65 genes (R65-HATG05poly). In vitro, TG05poly and both reassortants were able to replicate without the addition of trypsin, which is characteristic for HPAIV. Moreover, in contrast to avirulent TG05, the variants TG05poly, TG05-HAR65, and R65-HATG05poly are pathogenic in chicken to an increasing degree. Whereas the HA cleavage site mutant TG05poly led to temporary non-lethal disease in all animals, the reassortant TG05-HAR65 caused death in 3 of 10 animals. Furthermore, the reassortant R65-HATG05poly displayed the highest lethality as 8 of 10 chickens died, resembling “natural” HPAIV strains. Taken together, acquisition of a polybasic HA cleavage site is only one necessary step for evolution of low-pathogenic H5N1 strains into HPAIV. However, these low-pathogenic strains may already have cryptic virulence potential. Moreover, besides the polybasic cleavage site, the additional virulence determinants of H5N1 HPAIV are located within the HA itself and in other viral proteins