Animal models for basic and translational research in reconstructive transplantation

Reconstructive transplantation represents a bona fide option for select patients with devastating tissue loss, which could better restore the appearance, anatomy, and function than any other conventional treatment currently available. Despite favorable outcomes, broad clinical application of reconstructive transplantation is limited by the potential side effects of chronic multidrug immunosuppression. Thus, any reconstructive measures to improve these non‐life‐threatening conditions must address a delicate balance of risks and benefits. Today, several exciting novel therapeutic strategies, such as the implementation of cellular therapies including bone marrow or stem cells that integrate the concepts of immune regulation with those of nerve regeneration, are on the horizon. The development of reliable and reproducible small andlarge animal models is essential for the study of the unique immunological and biological aspects of vascularized composite allografts and to translate such novel immunoregulatory and tolerance‐inducing strategies and therapeutic concepts from the bench to bedside. This review provides an overview of the multitude of small and largeanimal models that have been particularly designed for basicand translational research related to reconstructive transplantation. (Part C) 96:39–50, 2012. © 2012 Wiley Periodicals, Inc.     

An information-theoretic analysis of genetics, gender and age in cancer patients

Germline genetics, gender and hormonal-signaling pathways are all well described modifiers of cancer risk and progression. Although an improved understanding of how germline genetic variants interact with other cancer risk factors may allow better prevention and treatment of human cancer, measuring and quantifying these interactions is challenging. In other areas of research, Information Theory has been used to quantitatively describe similar multivariate interactions. We implemented a novel information-theoretic analysis to measure the joint effect of a high frequency germline genetic variant of the p53 tumor suppressor pathway (MDM2 SNP309 T/G) and gender on clinical cancer phenotypes. This analysis quantitatively describes synergistic interactions among gender, the MDM2 SNP309 locus, and the age of onset of tumorigenesis in p53 mutation carriers. These results offer a molecular and genetic basis for the observed sexual dimorphism of cancer risk in p53 mutation carriers and a model is proposed that suggests a novel cancer prevention strategy for p53 mutation carriers.     

Pongamia pinnata: An Untapped Resource for the Biofuels Industry of the Future

Pongamia pinnata (L.) Pierre is a fast-growing leguminous tree with the potential for high oil seed production and the added benefit of the ability to grow on marginal land. These properties support the suitability of this plant for large-scale vegetable oil production required by a sustainable biodiesel industry. The future success of P. pinnata as a sustainable source of feedstock for the biofuels industry is dependent on an extensive knowledge of the genetics, physiology and propagation of this legume. In particular, research should be targeted to maximizing plant growth as it relates to oil biosynthesis. This review assesses and integrates the biological, chemical and genetic attributes of the plant, providing the basis for future research into Pongamia’s role in an emerging industry.     

Epigallocatechin gallate increases the formation of cytosolic lipid droplets and decreases the secretion of apoB-100 VLDL

Epigallocatechin gallate (EGCG) increases the formation of cytosolic lipid droplets by a mechanism that is independent of the rate of triglyceride biosynthesis and involves an enhanced fusion between lipid droplets, a process that is crucial for their growth in size. EGCG treatment reduced the secretion of both triglycerides and apolipoprotein B-100 (apoB-100) VLDLs but not of transferrin, albumin, or total proteins, indicating that EGCG diverts triglycerides from VLDL assembly to storage in the cytosol. This is further supported by the observed increase in both intracellular degradation of apoB-100 and ubiquitination of the protein (indicative of increased proteasomal degradation) in EGCG-treated cells. EGCG did not interfere with the microsomal triglyceride transfer protein, and the effect of EGCG on the secretion of VLDLs was found to be independent of the LDL receptor. Thus, our results indicate that EGCG promotes the accumulation of triglycerides in cytosolic lipid droplets, thereby diverting lipids from the assembly of VLDL to storage in the cytosol. Our results also indicate that the accumulation of lipids in the cytosol is not always associated with increased secretion of VLDL.     

Ethane oxidation by methane-oxidizing bacteria

The relationship between the rates of methane and ethane oxidation by washed suspensions of methane-oxidizing bacteria has been investigated. Considerable differences between bacterial strains were observed. Two closely related Methylomonas strains which differed in their oxidizing capacity were further investigated. The low ethane oxidation rate of one strain could be strongly stimulated by the addition of oxidizable co-substrates, and the presence of ethane stimulated formate oxidation. The other strain had a much higher ethane oxidation rate and stimulation by co-substrates was negligible.Differences between the levels of dissimilative enzymes in cell-free extracts could not be detected. Attempts to produce extracts with methane mono-oxygenase activity failed. When cells were made permeable with chitosan the results suggested that strains with a low ethane oxidizing capacity obtain the required reductant for the mono-oxygenase from endogenous respiration. In strains with a high ethane oxidation rate, the reductant appears to be derived from oxidation of ethanol or acetaldehyde.     

tRNA binding stabilizes rat liver 60 S ribosomal subunits during treatment with LiCl

We have shown recently that, in the absence of mRNA, 1 molecule of nonacylated tRNA binds to the large ribosomal subunit of rat liver with a high affinity constant (Buisson, M., Reboud, A.M., Dubost, S., and Reboud, J. P. (1979) Biochem. Biophys. Res. Commun. 90,634-640). In this paper, free and tRNA-bound 60 S subunits were treated with increasing concentrations of LiCl to obtain information on tRNA binding site. The rationale for using deacylated tRNA was that it is assumed to bind to the peptidyl donor site. We observed that tRNA has a strong protective effect on subunit modifications produced by LiCl: tRNA prevents subunit inactivation as measured by puromycin reaction and polyphenylalanine synthesis and it shifts the Li+/Mg2+ ratio value needed to reach 50% inactivation, from 60 to 250; it also prevents ribosomal protein and 5 S RNA release and large sedimentation changes of subunits, induced by LiCl. To explain the mechanism of 60 S subunit stabilization by tRNA, two hypotheses are considered: stabilization can be consequent on direct interaction of tRNA with specific proteins, or on maintenance on subunits of essential cations which are otherwise displaced by Li+, or both.     

The Relationship between Parental Depressive Symptoms,Family Type,and Adolescent Functioning

It is evident that parental depressive symptoms negatively influence adolescent behavior and various psychosocial outcomes. Certain family types like families with a chronically ill parent and single parent families are more vulnerable to parental depressive symptoms. However, the relationship between these symptoms, family type, and adolescent functioning remains largely unclear. This study examined relations between self-report of parental depressive symptoms and adolescent functioning in 86 two-parent families including a parent with a chronic medical condition, 94 families with healthy single parents, and 69 families with 2 healthy parents (comparison group). Parents completed the Beck Depression Inventory. Adolescents filled in the Youth Self-Report measuring problem behavior, and other instruments measuring psychosocial outcomes (stress, grade point average, school problems, and self-esteem). Multilevel analyses were used to examine the effects of family type, parental depressive symptoms, adolescents'' gender and age, and interaction effects on adolescent functioning. The results indicated that adolescents with chronically ill and single parents had a lower grade point average (p<.01) than the comparison group. Adolescents of single parents reported more internalizing problems (p<.01) and externalizing problems (p<.05) than children from the other family types. Parental depressive symptoms were strongly related to child report of stress (p<.001). Adolescents of depressed chronically ill parents were particularly vulnerable to internalizing problems (interaction effect, p<.05). Older children and girls, and especially older girls, displayed more internalizing problems and stress. It can be concluded that growing up with a chronically ill parent in a family with 2 parents may have less impact on adolescent problem behavior than growing up in a single parent family. Health practitioners are encouraged to be attentive to the unique and combined influence of family type and parental depressive symptoms on adolescent functioning. Older and female adolescents deserve particular attention.     

Spatial separation of litter decomposition and mycorrhizal nitrogen uptake in a boreal forest

Our understanding of how saprotrophic and mycorrhizal fungi interact to re-circulate carbon and nutrients from plant litter and soil organic matter is limited by poor understanding of their spatiotemporal dynamics. In order to investigate how different functional groups of fungi contribute to carbon and nitrogen cycling at different stages of decomposition, we studied changes in fungal community composition along vertical profiles through a Pinus sylvestris forest soil. We combined molecular identification methods with 14C dating of the organic matter, analyses of carbon:nitrogen (C:N) ratios and 15N natural abundance measurements. Saprotrophic fungi were primarily confined to relatively recently (< 4 yr) shed litter components on the surface of the forest floor, where organic carbon was mineralized while nitrogen was retained. Mycorrhizal fungi dominated in the underlying, more decomposed litter and humus, where they apparently mobilized N and made it available to their host plants. Our observations show that the degrading and nutrient-mobilizing components of the fungal community are spatially separated. This has important implications for biogeochemical studies of boreal forest ecosystems.     

Immunoglobulin G galactosylation and sialylation are associated with pregnancy-induced improvement of rheumatoid arthritis and the postpartum flare: results from a large prospective cohort study

Introduction  

Improvement of rheumatoid arthritis (RA) during pregnancy has been causatively associated with increased galactosylation of immunoglobulin G (IgG) N-glycans. Since previous studies were small, did not include the postpartum flare and did not study sialylation, these issues were addressed in the present study.