Transfer of Conditionability Between Planaria Through DNA and RNA

This experiment examined whether the transfer of DNA or RNA from conditioned planaria could make the recipients more susceptible to similar conditioning. It has been shown in prior experiments that cephalization is not necessary for memory retention in planaria, so there must be another, non-neural mechanism for memory. Thus, changes in DNA or RNA may be responsible for memory retention, and introducing these changes to naive planaria could transfer the "memory" of the conditioned donor. This study included 3 groups of 11 planaria: the control group, the DNA receival group, and the RNA receival group. After the control group was conditioned, each planarian’s RNA and DNA were extracted and given to its genetically identical counterparts in the DNA and RNA receival groups. The number of trials it took to condition the planaria in each group was measured and compared to see if the transfer of RNA or DNA made the recipients more easily conditionable than the control donor group. The results show that the transfer of RNA and DNA made insignificant changes to the conditionability of recipients. However, further research may be able to identify the location of memory bearing molecules, which, if applied to experiments similar to this one, would ensure that the planaria received a high enough concentration of genetic material for any changes present to make a significant effect.

Borrowing Sperm

Once it passes quality control, donor sperm is “released” to the thousands of couples who are involuntarily childless because of azoospermia. Chapter 6 shows how for those infertile couples who “borrow” sperm in China, secrecy is as vital as male infertility is taboo. Through fertility clinics, artificial insemination by donor (AID) emerges as an opportunity to achieve a visible pregnancy, a pregnancy that couples are both in pursuit of and expected to deliver by family and friends. The chapter argues that in one-child policy China, recipient couples and donors mobilize strategies of “hearth” management and trouble avoidance as third-party conception has become acceptable for increasing numbers of involuntarily childless couples who are living with male infertility.

Fetal Tolerance to Maternal Antigens Improves the Outcome of Allogeneic Bone Marrow Transplantation by a CD4+CD25+ T Cell-Dependent Mechanism.

The lack of donor availability is a major limitation to the widespread use of allogeneic HSCT and therefore it would be beneficial to identify permissible HLA mismatches. The maternal and fetal antigens which are transmitted through the bi-directional transplacental passage during pregnancy may induce tolerance to noninherited maternal antigens (NIMAs) in offspring and to inherited paternal antigens (IPAs) in the mother. Using mouse models of BMT, we investigated whether fetal-maternal tolerance could affect the outcome of allogeneic BMT. To generate NIMA-exposed mice, we used the F1 x P backcross breeding schema. A B6 (H-2b) male and a B6D2F1 (H-2b/d) female were mated to generate H-2b/b offspring that was exposed to NIMA-H-2d in utero. To generate IPA-exposed mice, a female B6 mouse was mated with a male B6D2F1 mouse and was exposed to IPA-H-2d from her H-2b/d offspring. First, to examine the influence of the NIMA/IPA exposure on the alloreactive T cell responses to the corresponding antigens in vitro, CD4+ T cells isolated from these mice were cultured with B6D2F1 stimulators. Proliferation and IFN-gamma production of T cells from NIMA-exposed mice in response to NIMAs were significantly reduced in comparison to those from the controls, but T cells from IPA-exposed mice did not reduce reactivity to IPAs. We then performed allogeneic BMT from NIMA-exposed donors. Lethally irradiated B6D2F1 mice were transplanted with 5x106 TCD BM from the control B6 mice together with 2x106 T cells from either 8 week-old NIMA-exposed or control B6 donors. GVHD mortality was significantly less in recipients of a NIMA-exposed donor than in those of a control donor (28% vs 84% on day 80, p<0.005). When transplanted to third-party B6C3F1 (H-2b/k) recipients, no protective NIMA effect was observed, thus demonstrating the antigen-specificity of the NIMA-effects. In contrast, BMT from an IPA-exposed donor did not reduce GVHD in comparison to BMT from a control donor. We then studied the effects of NIMA complementary transplantation on both subsequent T cell reconstitution and graft-versus-leukemia (GVL) effect. T cell reconstitution was significantly improved in NIMA-recipients in comparison to that in the allogeneic controls 40 days after BMT (p<0.05). The number of double positive thymocytes was also significantly higher in the recipients of NIMA-exposed donors than in those of the controls (p<0.05). In GVL experiments, 2.5x104 host-type P815 leukemia cells (H-2d), that were uniformly lethal to the recipients of syngeneic BMT by day 20 after BMT, were injected to recipients of allogeneic BMT on day 0. Allogeneic BMT from a control donor and a NIMA-exposed donor significantly delayed the leukemia relapse (p<0.005), thus demonstrating that NIMA complementary transplantation did not abrogate GVL effect. Lastly, we examined whether CD4+CD25+ T cells mediate the NIMA effect. The tolerogenic NIMA effect was completely abolished by the depletion of CD4+CD25+ cells from the donor inoculums, thus suggesting the involvement of CD4+CD25+ regulatory T cells in the tolerogenic NIMA effects. Our findings have profound implications on clinical HSCT, they suggest that the use of a NIMA-mismatched donor in the absence of a HLA-identical donor may be a potentially effective treatment strategy.

Evidence suggesting the regulation of a coagulation factor levels in rabbits by a transferable plasma agent

New Zealand white rabbits were given 30 ml of goat serum intravenously. This procedure resulted in an immediate decrease in platelet count, fibrinogen, and levels of coagulation factors II, V, VII, and X, due to consumption coagulopathy. These factors returned toward baseline levels approximately 12 hr after the injection. Plasma from rabbits who had received goat serum 48 hr previously (donor rabbits) was injected into recipient rabbits. This procedure resulted in a slight rise in the level of coagulation factor II (range, 20%-30%) and a significant rise in factors V (35%-75%), VII (35%-235%), and X (35%-75%) in the recipients. When plasma from control donor rabbits who had not received goat serum was injected into recipients, there was no change in these coagulation factors. It is postulated that the reduction in coagulation factor levels in donor rabbits induces a “coagulopoietin” for each factor or one “coagulopoietin” for all factors which stimulates increased synthesis and/or release of these factors in recipient rabbits.

Evidence suggesting the regulation of a coagulation factor levels in rabbits by a transferable plasma agent

New Zealand white rabbits were given 30 ml of goat serum intravenously. This procedure resulted in an immediate decrease in platelet count, fibrinogen, and levels of coagulation factors II, V, VII, and X, due to consumption coagulopathy. These factors returned toward baseline levels approximately 12 hr after the injection. Plasma from rabbits who had received goat serum 48 hr previously (donor rabbits) was injected into recipient rabbits. This procedure resulted in a slight rise in the level of coagulation factor II (range, 20%-30%) and a significant rise in factors V (35%-75%), VII (35%-235%), and X (35%-75%) in the recipients. When plasma from control donor rabbits who had not received goat serum was injected into recipients, there was no change in these coagulation factors. It is postulated that the reduction in coagulation factor levels in donor rabbits induces a “coagulopoietin” for each factor or one “coagulopoietin” for all factors which stimulates increased synthesis and/or release of these factors in recipient rabbits.