Evidence of silver eels contamination by microcystin‐LR at the onset of their seaward migration: what consequences for breeding potential?

Thirty migrating silver eels Anguilla anguilla were collected in a river system where algal blooms occurred yearly. Fifty per cent of eel livers were contaminated by microcystin-LR (mean ± s . d . toxin level: 28·1 ± 22·4 ng g⁻¹). Contaminated silver ( v. healthy) eels had lower fish condition. Consequences of this impact for the breeding potential of these migrating eels are discussed.     

Phosphoramidate protides of carbocyclic 2',3'-dideoxy-2',3'-didehydro-7-deazaadenosine with potent activity against HIV and HBV

Synthesis of phosphoramidate protides of carbocyclic D- and L-2',3'-dideoxy-2',3'-didehydro-7-deazaadenosine by treatment of the nucleoside with phosphorochloridates in the presence of pyridine and t-BuMgCl is described. Several of these protides showed significantly improved antiviral potency over the parent nucleosides against both HIV and HBV.     

Medfly (Diptera: Tephritidae) genetic sexing: large-scale field comparison of males-only and bisexual sterile fly releases in Guatemala

The effect of releases of bisexual (males and female) and unisexual (male only) sterilized medflies was compared in three large field evaluations over a 3-yr period (1995-1997) in southwestern Guatemala. The two strains tested were a genetic sexing strain, Vienna-4/Tol-94, carrying the temperature sensitive tsl gene to eliminate females in the egg stage, and the standard bisexual Petapa strain. Flies were mass-reared, sterilized by irradiation as pupae, shipped to a field center, and released by air as young adults over 2 km by 2 km core areas in the centers of separate 6 km by 6 km test plots. Strain performance was monitored weekly by trapping sterile and wild male adults in core and buffer areas and by collecting eggs from coffee berries to determine induced sterility. Results indicated a several-fold advantage for the males-only strain as measured by the level of induced sterility, especially at the very high release ratios of 100:1 recorded in 1997. During that final test year, sterile-fly release rates were increased to provide high sterile:wild (S:W) fly ratios in the field, and egg sterility reached levels in excess of 70% in plots were the male-only strain was used. However, in the plots where the bisexual strain was released, induced sterility only reached 12% despite S:W ratios above 1,000:1.     

IgG transcytosis and recycling by FcRn expressed in MDCK cells reveals ligand-induced redistribution

The neonatal Fc receptor (FcRn) transports IgG across epithelial cells and recycles serum IgG. FcRn binds IgG at the acidic pH of endosomes and releases IgG at the basic pH of blood. We expressed rat FcRn in polarized MDCK cells and demonstrated that it functions in transcytosis and recycling of IgG. In the absence of IgG, FcRn is distributed predominantly apically, but redistributes to basolateral locations upon IgG addition, indicating that ligand binding induces a signal that stimulates transcytosis. FcRn transcytoses IgG more efficiently in the apical to basolateral than the reverse direction when IgG is internalized by receptor-mediated endocytosis at acidic pH or by fluid phase endocytosis at basic pH. The PI 3-kinase inhibitor wortmannin disrupts basolateral recycling and transcytosis in both directions, but only minimally reduces apical recycling. Confocal imaging and quantitative IgG transport studies demonstrate that apically-internalized IgG recycles to the apical surface mainly from wortmannin-insensitive apical early endosomes, whereas FcRn-IgG complexes that transcytose to the basolateral surface pass through downstream Rab11-positive apical recycling endosomes and transferrin-positive common endosomal compartments.     

Using a logarithmic regression to identify the heart-rate threshold in cyclists

The purpose of this study was to establish an objective method for identifying the heart-rate threshold (HRT) in cyclists. Fifty-six male cyclists were tested on a cycle ergometer to volitional fatigue. Identification of the HRT used a heart-rate increase above a logarithmic regression line of best fit, coupled with the crossover of a linear regression line of best fit. The measures of Vco(2) and blood lactate for ventilatory threshold (VT) and lactate threshold (HLaT), respectively, were used as criterion measures to validate the HRT. Comparison of HRT with VT and HLaT showed significant associations (r = 0.98). Statistical variance between HRT, VT, and HLaT indicated no difference. From these findings, the logarithmic regression method provides an objective means to determine the HRT. Through this method, cyclists may obtain information for establishing accurate training levels and protocols.     

Gain of allelic gene expression for IGF-II occurs frequently in Barrett's esophagus

The IGF-II gene normally exhibits genomic imprinting, a DNA modification that allows the expression of only one of the two inherited alleles. With loss of imprinting, there is a gain of allelic gene expression (GOAGE) due to IGF-II being expressed by both alleles. GOAGE for IGF-II has been demonstrated in a number of malignancies and in normal epithelia surrounding malignancies, but not in epithelia without associated neoplasia. We hypothesized that nonneoplastic Barrett's epithelium might have GOAGE for IGF-II that could facilitate its progression to neoplasia. Endoscopic biopsies were obtained from metaplastic esophageal, normal gastric, and normal duodenal epithelia from 43 patients with Barrett's esophagus. Genomic DNA were analyzed using PCR followed by ApaI restriction enzyme digestion or allele-specific PCR to identify an ApaI polymorphism of IGF-II. cDNA from patients with the ApaI polymorphism were analyzed for IGF-II GOAGE using exon connection PCR, followed by a secondary nested PCR and ApaI restriction enzyme digestion. We found that 13 (30%) of 43 samples of Barrett's metaplasia contained the ApaI polymorphism and were thus informative for IGF-II, and sufficient material was available for GOAGE analysis in 9 of those 13 cases. GOAGE for IGF-II was demonstrated in five (56%) of those nine cases. All patients with GOAGE in Barrett's metaplasia also demonstrated GOAGE in the gastric and duodenal epithelia. In contrast, patients without GOAGE in Barrett's metaplasia also had no GOAGE in their gastric and duodenal epithelia. We conclude that in patients with Barrett's esophagus, GOAGE for IGF-II is found frequently in the metaplastic esophageal epithelium as well as in normal gastric and duodenal epithelia.     

Protein pathway activation mapping of brain metastasis from lung and breast cancers reveals organ type specific drug target activation

Brain metastases are the most common fatal complication of systemic cancer, especially of lung (40-50%) and breast (20-30%) cancers. In this era of personalized therapy, there is a critical need to uncover the signaling architecture of brain metastases; however, little is known about what signaling pathways are activated in the context of the brain microenvironment. Using a unique study set of 42 brain metastases from patients with breast or nonsmall cell lung cancer (NSCLC), the phosphorylation/activation states of 128 key signaling proteins involved in cancer signaling were measured in laser capture microdissected tumor epithelium using reverse phase protein microarray (RPMA) technology. Distinct pathway activation subgroups from both breast and lung metastases were underpinned by, among others, ERBB2, AKT, mTOR, EGFR, SMAD, and ERK-p38 signaling. Breast cancer metastases showed significantly (p < 0.05) higher activation of the c-ERBB2/IGFR-AKT pathway network compared to NSCLC metastases, whereas NSCLC metastases to the brain exhibited higher relative levels of many members of the EGFR-ERK signaling network. Protein pathway activation mapping using RPMA revealed both the heterogeneity of signaling networks in brain metastases that would require a prior stratification to targeted therapies as well as the requirement of direct analysis of the metastatic lesion.