Anchorless prion protein results in infectious amyloid disease without clinical scrapie

In prion and Alzheimer's diseases, the roles played by amyloid versus nonamyloid deposits in brain damage remain unresolved. In scrapie-infected transgenic mice expressing prion protein (PrP) lacking the glycosylphosphatidylinositol (GPI) membrane anchor, abnormal protease-resistant PrPres was deposited as amyloid plaques, rather than the usual nonamyloid form of PrPres. Although PrPres amyloid plaques induced brain damage reminiscent of Alzheimer's disease, clinical manifestations were minimal. In contrast, combined expression of anchorless and wild-type PrP produced accelerated clinical scrapie. Thus, the PrP GPI anchor may play a role in the pathogenesis of prion diseases.     

Direct observations of North Pacific ventilation: brine rejection in the Okhotsk Sea

Brine rejection that accompanies ice formation in coastal polynyas is responsible for ventilating several globally important water masses in the Arctic and Antarctic. However, most previous studies of this process have been indirect, based on heat budget analyses or on warm-season water column inventories. Here, we present direct measurements of brine rejection and formation of North Pacific Intermediate Water in the Okhotsk Sea from moored winter observations. A steady, nearly linear salinity increase unambiguously caused by local ice formation was observed for more than a month.     

Intratesticular lidocaine reduces the response to surgical castration in dogs

ObjectiveTo investigate whether intratesticular injection of lidocaine pre-surgery would reduce the intraoperative responses to elective castration in dogs.Study designDouble-blinded, randomized, controlled, prospective clinical study.AnimalsForty-two client-owned dogs weighing 2.2–38.4 kg and aged between 4.5 and 56 months.MethodsGroup L dogs received an intratesticular injection of 2% lidocaine (2 mg kg^?1) and Group S an identical volume of saline prior to surgery. Premedication was with acepromazine and morphine intramuscularly. Anaesthesia was induced with propofol intravenously and maintained with isoflurane vaporized in oxygen. Heart rate (HR), mean arterial pressure (MAP), respiratory rate (f_R), end-tidal isoflurane (Fe′ISO) and carbon dioxide concentrations, oxygen saturation and ECG were monitored during surgery. Fe′ISO was maintained at 1.0 ± 0.1%. Supplemental propofol was given in response to gross movement.ResultsGroup L had significantly lower maximum values for both HR and MAP. Group L displayed significantly smaller increases in HR during exteriorization of the first testis than Group S. There was an overall significant difference in MAP between groups during all surgical events (p = 0.041) and time points (p = 0.002). In univariate analysis, Group L showed significantly less changes in MAP during skin incision, exteriorization of the first testis and clamping of both spermatic cords. Group S reached its highest f_R significantly earlier. Group L (eight dogs) required additional propofol 33 ± 18 minutes after the start of surgery and Group S (seven dogs) at 19 ± 17 minutes; this difference was not statistically significant. Seven dogs in Group L and 12 dogs in Group S required rescue analgesia with morphine (GCMPS-SF score ≥6); this difference was not statistically significant. No adverse effects were reported postoperatively.Conclusions and clinical relevanceBased on this study, the authors recommend the use of intratesticular lidocaine for surgical castration in dogs.