Cloning, expression and characterization of monkey (Macaca fascicularis) CD137

CD137 plays an important role as a co-stimulatory molecule in activated T cells. Agonistic CD137 specific antibodies have been investigated as therapeutic agents to promote tumor-specific immune responses by direct activation of T cells. As part of the pre-clinical pharmacological evaluation of cynomolgus monkeys, monkey CD137 was cloned and characterized. The deduced amino acid sequence encoded a full-length gene of 254 amino acids 95% identical to human CD137. Sequence variants identified in monkey CD137 include four splice variants lacking the transmembrane domain. These variants were detectable in human including two previously unreported variants. Two missense single nucleotide polymorphisms were detected present in 42 and 50% of 36 monkeys tested. In both monkey and human, mRNA expression of full-length CD137 and splice variants were significantly increased in peripheral blood mononuclear cells (PBMCs) upon stimulation by anti-CD3 antibodies. Recombinant monkey CD137 protein was bound with high affinity by an agonistic anti-human CD137 antibody but not by an anti-mouse CD137 antibody. In summary, compared to human, monkey CD137 showed distinct extracellular domain amino acid sequence and sequence polymorphisms. Thus, antibodies directed against epitopes in this extracellular domain could have differences in pharmacologic activity between cynomolgus monkeys and human or across individual cynomolgus monkeys.     

Local orbital forcing of antarctic climate change during the last interglacial

During the last interglacial, Antarctic climate changed before that of the Northern Hemisphere. Large local changes in precession forcing could have produced this pattern if there were a rectified response in sea ice cover. Results from a coupled sea ice-ocean general circulation model supported this hypothesis when it was tested for three intervals around the last interglacial. Such a mechanism may play an important role in contributing to phase offsets between Northern and Southern Hemisphere climate change for other time intervals.     

Isotype- and subclass-specific responses to infection and reinfection with parainfluenza-3 virus: comparison of the diagnostic potential of ELISAs detecting seroconversion and specific IgM and IgA.

Isotype- and subclass-specific indirect enzyme-linked immunosorbent assays were developed to detect parainfluenza-3 virus-specific IgG1, IgG2, IgM, and IgA responses. Sera were treated with protein G-agarose prior to testing for specific IgM and IgA to eliminate the possibility of false-positive results due to IgM-rheumatoid factor and to remove interisotypic competition due to specific IgG. IgM and IgA absorbance values were expressed as a percentage of the absorbance values of positive reference sera included on each plate (S/P%), and respective positive/negative threshold values of 15.0% and 28.0% were determined. The mean interval between experimental infection of 3 calves and initial detection of specific IgG1 and IgG2 responses was 8.0 and 9.3 days respectively, rising rapidly to an initial plateau 13.7 and 11.0 days postinfection (dpi). Reinfection of these calves at 30 dpi resulted in further rapid increases, with higher plateau values reached 13.0 (IgG1) and 13.7 (IgG2) days later. The mean interval between infection and the first positive IgM and IgA responses was 6.7 and 12.3 days, respectively. IgM S/P% values peaked at 13.0 dpi, with all 3 calves showing a secondary anamnestic response to reinfection, peaking 4.7 days later. The IgA response to initial infection was weak, with only 2 calves showing an obvious peak response at 15.0 dpi. A strong anamnestic IgA response to reinfection occurred in 2 calves, with a peak response 9.5 days later. Apparent biphasic and triphasic IgM and IgA responses were evident in some calves. Acute and convalescent serum samples from 80 calves involved in 17 outbreaks of respiratory disease were tested for specific IgM and IgA. Positive IgM results were detected in 15 outbreaks, with 71 sera from 44 calves testing positive. Although IgA-positive results were detected in the same 15 outbreaks, only 42 sera from 31 calves were positive. In a previous study, seroconversion was detected in 21 of these calves from 10 outbreaks. Thus the diagnostic potential of the assays was in the order IgM > IgA > seroconversion. The correlations between IgM and IgA, IgM and seroconversion, and IgA and seroconversion results for each calf were 73.8%, 58.8% and 62.5%, respectively.     

Immobilization of goitred gazelles (Gazella subgutterosa) and Arabian mountain gazelles (Gazella gazella) with xylazine-ketamine.

Xylazine combined with ketamine successfully immobilized free-ranging and captive goitred gazelles (Gazella subgutterosa) and Arabian mountain gazelles (Gazella gazella). One hundred thirty immobilizations were performed on 58 individuals. When administered i.m. via dart to free-ranging gazelles, xylazine (125 mg/ml) combined with ketamine (100 mg/ml) produced smooth induction and recovery. Mountain gazelles required higher dosages (11.7-15.2 mg/kg xylazine and 9.3-12.2 mg/kg ketamine) than goitred gazelles (6.8-7.4 mg/kg xylazine and 5.4-5.9 mg/kg ketamine). For manually restrained captive gazelles of both species, i.v. xylazine (11 mg/ml) combined with i.v. ketamine (44 mg/ml) immobilized the gazelles at considerably lower doses (0.4-1.0 mg/kg xylazine and 1.4-3.9 mg/kg ketamine). These anesthetic combinations are useful alternatives to ultrapotent narcotics in these gazelle species.