A double-edged sword: parental care increases risk of offspring infection by a maternally vectored parasite

Parental care can protect offspring from predators but can also create opportunities for parents to vector parasites to their offspring. We hypothesized that the risk of infection by maternally vectored parasites would increase with the frequency of mother–offspring contact. Ammophila spp. wasps (Hymenoptera: Sphecidae) build nests in which they rear a single offspring. Ammophila species exhibit varied offspring provisioning behaviours: some species enter the nest once to provision a single, large caterpillar, whereas others enter the nest repeatedly to provision with many smaller caterpillars. We hypothesized that each nest visit increases the risk of offspring parasitism by Paraxenos lugubris (Strepsiptera: Xenidae), whose infectious stages ride on the mother wasp (phoresy) to reach the vulnerable Ammophila offspring. We quantified parasitism risk by external examination of museum-curated Ammophila specimens—the anterior portion of P. lugubris protrudes between the adult host''s abdominal sclerites and reflects infection during the larval stage. As predicted, Ammophila species that receive larger numbers of provisions incur greater risks of parasitism, with nest provisioning behaviour explaining ca 90% of the interspecific variation in mean parasitism. These findings demonstrate that parental care can augment, rather than reduce, the risk of parasite transmission to offspring.     

Absence of replication of porcine endogenous retrovirus and porcine lymphotropic herpesvirus type 1 with prolonged pig cell microchimerism after pig-to-baboon xenotransplantation

Porcine endogenous retrovirus (PERV), porcine cytomegalovirus (PCMV), and porcine lymphotropic herpesvirus (PLHV) are common porcine viruses that may be activated with immunosuppression for xenotransplantation. Studies of viral replication or transmission are possible due to prolonged survival of xenografts in baboon recipients from human decay-accelerating factor transgenic or alpha-1,3-galactosyltransferase gene knockout miniature swine. Ten baboons underwent xenotransplantation with transgenic pig organs. Graft survival was 32 to 179 days. Recipient serial samples of peripheral blood mononuclear cells (PBMC) and plasma were analyzed for PCMV, PERV, and PLHV-1 nucleic acids and viral replication using quantitative PCR assays. The PBMC contained PERV proviral DNA in 10 animals, PLHV-1 DNA in 6, and PCMV in 2. PERV RNA was not detected in any PBMC or serum samples. Plasma PLHV-1 DNA was detected in one animal. Pig cell microchimerism (pig major histocompatibility complex class I and pig mitochondrial cytochrome c oxidase subunit II sequences) was present in all recipients with detectable PERV or PLHV-1 (85.5%). Productive infection of PERV or PLHV-1 could not be demonstrated. The PLHV-1 viral load did not increase in serum over time, despite prolonged graft survival and pig cell microchimerism. There was no association of viral loads with the nature of exogenous immune suppression. In conclusion, PERV provirus and PLHV-1 DNA were detected in baboons following porcine xenotransplantation. Viral detection appeared to be due to persistent pig cell microchimerism. There was no evidence of productive infection in recipient baboons for up to 6 months of xenograft function.     

Clinically Relevant Concentration Determination of Inhaled Anesthetics (Halothane,Isoflurane, Sevoflurane,and Desflurane) by <Superscript>19</Superscript>F NMR

Biophysical studies of protein–anesthetic interactions using nuclear magnetic resonance (NMR) spectroscopy are often conducted by the addition of micro amounts of neat inhaled anesthetic which yields much higher than clinically relevant (0.2–0.5 mM) anesthetic concentrations. We report a ¹⁹F NMR technique to measure clinically relevant inhaled anesthetic concentrations from saturated aqueous solutions of these anesthetics (halothane, isoflurane, sevoflurane, and desflurane). We use a setup with a 3-mm NMR tube (containing trifluoroacetic acid as standard), coaxially inserted in a 5-mm NMR tube containing anesthetic solution under investigation. All experiments are conducted in a 5-mm NMR probe. We also have provided standard curves for four inhaled anesthetics using NMR technique. The standard curve for each of these anesthetics is helpful in determining the prerequisite amount of aqueous anesthetic solution required to prepare clinically relevant concentrations for protein–anesthetic interaction studies. Parts of the results to be presented at Society for Neuroscience meeting, 2008.     

Conditional MLL-CBP targets GMP and models therapy-related myeloproliferative disease

Chromosomal translocations that fuse the mixed lineage leukemia (MLL) gene with multiple partners typify acute leukemias of infancy as well as therapy-related leukemias. We utilized a conditional knockin strategy to bypass the embryonic lethality caused by MLL-CBP expression and to assess the immediate effects of induced MLL-CBP expression on hematopoiesis. Within days of activating MLL-CBP, the fusion protein selectively expanded granulocyte/macrophage progenitors (GMP) and enhanced their self-renewal/proliferation. MLL-CBP altered the gene expression program of GMP, upregulating a subset of genes including Hox a9. Inhibition of Hox a9 expression by RNA interference demonstrated that MLL-CBP required Hox a9 for its enhanced cell expansion. Following exposure to sublethal gamma-irradiation or N-ethyl-N-nitrosourea (ENU), MLL-CBP mice developed myelomonocytic hyperplasia and progressed to fatal myeloproliferative disorders. These represented the spectrum of therapy-induced acute myelomonocytic leukemia/chronic myelomonocytic leukemia/myelodysplastic/myeloproliferative disorder similar to that seen in humans possessing the t(11;16). This model of MLL-CBP therapy-related myeloproliferative disease demonstrates the selectivity of this MLL fusion for GMP cells and its ability to initiate leukemogenesis in conjunction with cooperating mutations.     

Gene Duplication and the Evolution of Hemoglobin Isoform Differentiation in Birds

The majority of bird species co-express two functionally distinct hemoglobin (Hb) isoforms in definitive erythrocytes as follows: HbA (the major adult Hb isoform, with α-chain subunits encoded by the α^A-globin gene) and HbD (the minor adult Hb isoform, with α-chain subunits encoded by the α^D-globin gene). The α^D-globin gene originated via tandem duplication of an embryonic α-like globin gene in the stem lineage of tetrapod vertebrates, which suggests the possibility that functional differentiation between the HbA and HbD isoforms may be attributable to a retained ancestral character state in HbD that harkens back to a primordial, embryonic function. To investigate this possibility, we conducted a combined analysis of protein biochemistry and sequence evolution to characterize the structural and functional basis of Hb isoform differentiation in birds. Functional experiments involving purified HbA and HbD isoforms from 11 different bird species revealed that HbD is characterized by a consistently higher O₂ affinity in the presence of allosteric effectors such as organic phosphates and Cl⁻ ions. In the case of both HbA and HbD, analyses of oxygenation properties under the two-state Monod-Wyman-Changeux allosteric model revealed that the pH dependence of Hb-O₂ affinity stems primarily from changes in the O₂ association constant of deoxy (T-state)-Hb. Ancestral sequence reconstructions revealed that the amino acid substitutions that distinguish the adult-expressed Hb isoforms are not attributable to the retention of an ancestral (pre-duplication) character state in the α^D-globin gene that is shared with the embryonic α-like globin gene.     

Androgens stimulate specific aspects of maternal nest-building and reduce food intake in rabbits

Fluctuations in the plasma concentration of estradiol, progesterone, and prolactin across pregnancy regulate maternal nest-building (digging, straw-carrying, and hair-plucking) and food intake in rabbits. Because testosterone levels also change through pregnancy, we investigated if the injection of testosterone propionate (TP; 1 or 5 mg/day) or 5alpha-dihydrotestosterone propionate (5 or 10 mg/day) for 20 days, alone and combined with progesterone (P; 10 mg/day from days 2 to 15), modulated nest-building and food intake in ovariectomized rabbits. Only the combined injection of TP (5 mg/day) plus P stimulated digging and no treatment promoted straw-carrying or hair-plucking. Both androgens induced hair-loosening from the ventrum, an effect counteracted by P. High doses of TP and 5alpha-dihydrotestosterone propionate reduced food intake by 60-70% of baseline values; this effect was counteracted by P in TP-treated animals. These results support a participation of androgens in specific aspects of maternal nest-building and reveal a strong inhibitory effect on food intake.     

Reforestation: A potential approach to mitigate excess atmospheric CH4 build‐up

Summary Methane (CH₄) is a very dangerous greenhouse gas, and its atmospheric concentration is rising due to natural and anthropogenic disturbances. Anthropogenic disturbances such as forest clearing, land‐use changes and farming practices all result in considerable increases in N inputs and alterations in soil properties, including the CH₄ sink potential of the soil. Forest soils contribute to the consumption of CH₄ due to the presence of methanotrophic bacteria. It is proposed that the restoration of degraded forest ecosystems or unused degraded land may significantly contribute to the recovery of methanotrophic activity in the soil and thereby the soil CH₄ sink potential.