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compared to those in hibernation serum (p=0.0103). OCN gene expression increasedfrom 0.055+0.004 in osteoblasts cultured in hibernation serum to 0.098+0.01 inosteoblasts cultured in post-hibernation serum; there was no difference in OCNexpression between cells cultured in prehibernation serum and those in hibernationserum (p
factors Runx2 and OCN also increase in osteoblasts differentiated in post-hibernationserum, further supporting the idea of increased osteoblast activity in this season.In summary, the gene expression studies suggest that factors circulating in bearsin the weeks immediately following hibernation promote a hypermetabolic state inosteoblasts. Differentiated osteoblasts have higher expression of ubiquitin anddifferentiation markers, suggesting active protein metabolism and bone formation duringpost-hibernation. Undifferentiated osteoblasts have higher expression of Akt and CyclinD1, suggesting active proliferation of osteoblasts during post-hibernation. These data fitan earlier report of high bone turnover rate in spring-time bears [35].6.5 Tables and figuresTable 6.1—Summary of assaysThe number of bears and assays that were performed in each hibernation season. Thenumber of bears that gave birth to cubs is in parentheses. Unknown values are indicated as“UK.” Assays in undifferentiated cells are labeled “UD,” and assays in differentiated cells arelabeled “D.”Season BearsAge(years)AssaysData Location2006‐2007 2 (1) UK 3hr UD, 3hr D, 24hr UD, 6 day D Table 6.2‐6.52007‐2008 4 (3) 5‐14 24hr UD Table 6.497
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EXPLORATION OF THE ROLE OF SERUM FA
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Table of contentsIndex of Figures .
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Chapter Four - Attempts to find an
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Index of figures1.1. Simplified sch
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6.17. Longitudinal analysis of OPG
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6.49. Longitudinal analysis of ColI
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A.2. Complete list of BSALP correla
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List of abbreviationsα-MEM. Alpha-
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PCR. Polymerase chain reactionPer1
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G2/M checkpoint. The point in the c
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Species names13-lined ground squirr
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Chapter One - Background and signif
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1.3 Bone turnover is unbalanced dur
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pro-apoptosis regulator BAX. An imp
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low-dose administration of parathyr
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decrease in bone trabecular thickne
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experience periodic arousals in whi
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ears must have evolved a mechanism
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1.7.6 Hypothesis 2: OCN interacts w
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ain, heart, and femoral muscle of h
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Hypothesis 3a: Serum concentrations
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were released. Behavior indicating
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2.3 ResultsSerum activity of the bo
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(p
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post-hibernation sampling in the be
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also unclear whether ucOCN may affe
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atios of intact to fragmented OCN m
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Table 2.3—Bone marker “seasonal
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Table 2.7—Chemistry panel “seas
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ABNormalized BSALPBSALP (U/L)CO N D
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Total Calcium (mg/dL)A1.21.151.11.0
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ABTotal OCN (ng/mL)150100500O N D J
Page 67 and 68: Adiponectin (ng/mL)AB40003500300025
Page 69 and 70: ABNormalized InsulinInsulin (μU/mL
Page 71 and 72: surrounding and encompassing hibern
Page 73 and 74: decreased from 788+30 ng/mL in preh
Page 75 and 76: 120-122]. Most small hibernators ar
Page 77 and 78: ears. Similarly, serum NPY increase
Page 79 and 80: Table 3.2—Serum factor longitudin
Page 81 and 82: Leptin (ng/mL)ABO N D J F M A M O N
Page 83 and 84: Norepinephrine (ng/mL)A807060504030
Page 85 and 86: IGF‐1 (ng/mL)AN D J F M A MB10009
Page 87 and 88: 2008. Samples were collected as des
Page 89 and 90: sampling points. It is possible to
Page 91 and 92: C‐Terminal PTH (Relative)AB504030
Page 93 and 94: Chapter Five — Serum from hiberna
Page 95 and 96: Synergy HT Multi-Detection Micropla
Page 97 and 98: gene specific primers and 12.5 μL
Page 99 and 100: involved in the reduced caspase-3/7
Page 101 and 102: hibernation cycles without problem
Page 103 and 104: filtered seasonal bear serum and fo
Page 105 and 106: which is dependent upon caspase-3 a
Page 107 and 108: Caspase‐3/7 ActivityO N D J F M A
Page 109 and 110: 6Caspase‐3/7 Activity54321**0Vehi
Page 111 and 112: ABCaspase‐3/7 Activity9876543210*
Page 113 and 114: eyond the G1/S checkpoint, thus ind
Page 115 and 116: ears, it is possible that tissue se
Page 117: PTH1R, RANKL, Runx2, Smurf1, TLR4,
Page 121 and 122: Table 6.3—Gene expression 3 hour
Page 123 and 124: Table 6.5—Gene expression 6 day d
Page 125 and 126: Cyclin D1 Gene ExpressionO N D J F
Page 127 and 128: Smurf1 Gene ExpressionO N D J F M A
Page 129 and 130: BAK Gene ExpressionO N D J F M A MM
Page 131 and 132: M‐CSF Gene ExpressionO N D J F M
Page 133 and 134: Per1 Gene ExpressionO N D J F M A M
Page 135 and 136: Akt Gene ExpressionO N D J F M A MM
Page 137 and 138: Bcl‐2 Gene ExpressionO N D J F M
Page 139 and 140: Cyclin D1 Gene ExpressionO N D J F
Page 141 and 142: OPN Gene ExpressionO N D J F M A MM
Page 143 and 144: 2PTH1R Gene Expression1.510.50O N D
Page 145 and 146: TLR4 Gene ExpressionO N D J F M A M
Page 147 and 148: Bcl‐2 Gene ExpressionO N D J F M
Page 149 and 150: OCN Gene ExpressionO N D J F M A MM
Page 151 and 152: PTH1R Gene ExpressionO N D J F M A
Page 153 and 154: TLR4 Gene ExpressionO N D J F M A M
Page 155 and 156: condition in renal patients in whic
Page 157 and 158: hibernation. This report brings to
Page 159 and 160: 14. Kaneps, A.J., S.M. Stover, and
Page 161 and 162: 41. Chowdhury, I., B. Tharakan, and
Page 163 and 164: 68. Ashe, M.C., et al., Bone geomet
Page 165 and 166: 95. Perrien, D.S., et al., Aging al
Page 167 and 168: 122. Lesser, R.W., et al., Renal re
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151. Confavreux, C.B., R.L. Levine,
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178. Toribara, T.Y., A.R. Terepka,
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206. Luo, X.H., et al., Adiponectin
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233. Florant, G.L., et al., Fat-cel
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259. Bhasin, S., et al., Older men
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284. Miura, M., et al., A crucial r
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Appendix A—Complete tables of cor
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Table A.5—Complete list of ionize
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Table A.7—Complete list of adipon
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Table A.12—Complete list of norep
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