Comparative Analyses by Sequencing of Transcriptomes during Skeletal Muscle Development between Pig Breeds Differing in Muscle Growth Rate and Fatness

Understanding the dynamics of muscle transcriptome during development and between breeds differing in muscle growth is necessary to uncover the complex mechanism underlying muscle development. Herein, we present the first transcriptome-wide longissimus dorsi muscle development research concerning Lantang (LT, obese) and Landrace (LR, lean) pig breeds during 10 time-points from 35 days-post-coitus (dpc) to 180 days-post-natum (dpn) using Solexa/Illumina's Genome Analyzer. The data demonstrated that myogenesis was almost completed before 77 dpc, but the muscle phenotypes were still changed from 77 dpc to 28 dpn. Comparative analysis of the two breeds suggested that myogenesis started earlier but progressed more slowly in LT than in LR, the stages ranging from 49 dpc to 77 dpc are critical for formation of different muscle phenotypes. 595 differentially expressed myogenesis genes were identified, and their roles in myogenesis were discussed. Furthermore, GSK3B, IKBKB, ACVR1, ITGA and STMN1 might contribute to later myogenesis and more muscle fibers in LR than LT. Some myogenesis inhibitors (ID1, ID2, CABIN1, MSTN, SMAD4, CTNNA1, NOTCH2, GPC3 and HMOX1) were higher expressed in LT than in LR, which might contribute to more slow muscle differentiation in LT than in LR. We also identified several genes which might contribute to intramuscular adipose differentiation. Most important, we further proposed a novel model in which MyoD and MEF2A controls the balance between intramuscular adipogenesis and myogenesis by regulating CEBP family; Myf5 and MEF2C are essential during the whole myogenesis process while MEF2D affects muscle growth and maturation. The MRFs and MEF2 families are also critical for the phenotypic differences between the two pig breeds. Overall, this study contributes to elucidating the mechanism underlying muscle development, which could provide valuable information for pig meat quality improvement

Studies directed toward the total synthesis of tedanolide and studies of conformationally controlled E2 elimination reactions in acyclic systems.

This dissertation describes research directed toward the total synthesis of the marine natural product tedanolide; specifically focusing on the synthesis of a C(1)--C(12) fragment that will be used in a highly selective methyl ketone aldol reaction. In addition to these efforts, studies concerning the regioselectivity of conformationally controlled E2 elimination reactions in acyclic systems is discussed. At the outset of the synthesis of the C(1)--C(12) fragment of tedanolide, it was envisioned that a highly regioselective E2 elimination reaction could be utilized to install the C(8)--C(9) E-trisubstituted olefin. Unfortunately, it was discovered that steric shielding coupled with free rotation around the polypropionate backbone resulted in the highly selective formation of the undesired Z-oelfin. Therefore, it was necessary to design a polypropionate system that would provide a better model for the synthesis of E-trisubstituted olefins. This was accomplished by the synthesis of a ten carbon chain with methyl substituents at C(2,4,6 and 8; having a 1,3 anti relationship) and oxygen substituents at C(3,5 and 7; having a 1,3 anti relationship). The activation of the C(5) hydroxyl by its transformation to a mesylate allowed for an extensive study on the regioselectivity of an E2 elimination governed by conformational control through steric interactions. The E2 elimination did prove to be selective, however, a predominating Grob fragmentation limited the scope and utility of this methodology. Ultimately, this methodology was abandoned and an emphasis was placed on the synthesis of the C(1)--C(12) fragment through more traditional synthetic methods. During the synthesis of the C(1)--C(12) fragment of tedanolide vinyl anion, Horner-Wadsworth-Emmons and aldol coupling strategies were examined. Finally, a selective ethyl ketone aldol reaction for the installation of the C(6)--C(7) bond afforded the most concise and selective synthesis of the C(1)--C(12) fragment. Coupling of the C(1)--C(12) methyl ketone fragment with the C(13)--C(21) aldehyde fragment proved to be efficient and highly selective. Examination of post coupling modifications provided insight into the final strategy of the tedanolide synthesis, but were ultimately unsuccessful.Ph.D.Organic chemistryPure SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/130244/2/3042141.pd

Studies on the Synthesis of Tedanolide. 2. Stereoselective Synthesis of a Protected C(1)−C(12) Fragment

Highly diastereoselective syntheses of diketo esters 6a and 6b are described. These intermediates undergo efficient aldol reactions with protected C(13)−C(21) aldehydes 3 and 23, thereby providing advanced C(1)−C(21) tedanolide seco ester precursors 9a and 9b

Studies on the Synthesis of Tedanolide. 2. Stereoselective Synthesis of a Protected C(1)−C(12) Fragment

Highly diastereoselective syntheses of diketo esters 6a and 6b are described. These intermediates undergo efficient aldol reactions with protected C(13)−C(21) aldehydes 3 and 23, thereby providing advanced C(1)−C(21) tedanolide seco ester precursors 9a and 9b