Variable definitions.

Variable definitions.</p

One period lag—benchmark regression robustness test.

One period lag—benchmark regression robustness test.</p

The mediating role of CSR.

The mediating role of CSR.</p

Correlation coefficient test of each variable.

Correlation coefficient test of each variable.</p

One period of lag—a robustness test of the mediation effect.

One period of lag—a robustness test of the mediation effect.</p

Additional file 2: of Type 2 diabetes mellitus and risk of colorectal adenoma: a meta-analysis of observational studies

The MOOSE list of this meta-analysis. (DOCX 19 kb

<i>rsc</i> mutants exhibit phenotypes defective in mitochondrial function.

<p><b>(A)</b><i>rsc</i> mutants exhibit growth defects on medium containing a non-fermentable carbon source. Five-fold serial dilutions of individual strains (WT (BY4743), <i>nps1-105</i> (BYI-17), <i>nps1-13</i> (BYI-3), <i>rsc1Δ</i> (BYI-1), <i>rsc2Δ</i> (BYI-2), and <i>rsc7Δ</i> (BYI-18)) were grown to log phase in YPD medium, spotted on YPD and YPEG plates, and incubated at the indicated temperatures for 3 days. <b>(B)</b> Overexpression of <i>RSC1</i> suppresses the growth defect of <i>rsc2Δ</i> on YPEG. Five-fold serial dilutions of exponentially growing individual strains (WT (BY4743) carrying YEp13 (WT/vector) and <i>rsc2Δ</i> (BYI-2) carrying YEp13 (<i>rsc2Δ</i>/vector) or YEp13<i>RSC1</i>-3MYC (<i>rsc2Δ/RSC1</i>)) were spotted on YPD and YPEG plates and incubated at 30°C for 3 days. <b>(C)</b><i>rsc</i> mutants contain mitochondria with irregular morphologies. WT (BY4743), <i>nps1-13</i> (BYI-3), <i>rsc2Δ</i> (BYI-2), and <i>rsc7Δ</i> (BYI-18) cells were grown to log phase in YPD medium, stained with Mito-Tracker, and observed under a fluorescence microscope. Numerals on the right sides of panels represent the percentages of cells containing aggregated mitochondria among total cells. All <i>P</i>-values were calculated using the two-tailed chi-square test (≥50 cells; **<i>P</i> < 0.05, ***<i>P</i> < 0.005). <b>(D)</b><i>rsc</i> mutations enhance mitochondrial DNA loss. WT (BY4743), <i>nps1-105</i> (BYI-17), <i>nps1-13</i> (BYI-3), <i>rsc2Δ</i> (BYI-2), and <i>rsc7Δ</i> (BYI-18) cells were plated on YPEG medium; three independent colonies were later picked and separately grown to stationary phase in YPD medium. Two hundred cells from each culture were plated on YPD plates and incubated at 30°C for 3 days. To assess the frequency of petite cells, we counted the total number of cells and the number of petite cells on each plate. Data are presented as the means ± SEM of three replicates. <b>(E)</b><i>nps1-13</i> cells accumulate reactive oxygen species. WT (BY4743) and <i>nps1-13</i> (BYI-3) cells harboring pRS426 (WT/v and <i>nps1-13</i>/v, respectively) or pRS426<i>GPDpr</i>::<i>HAP4</i> (WT/<i>HAP4</i> and <i>nps1-13/HAP4</i>, respectively) were grown to log phase in SD-Ura medium, shifted to YPEG medium, and incubated at 30°C with shaking. On the indicated days, portions of the cells were separated, stained with dihydroethidium, and examined under a fluorescence microscope. The experiment was repeated three times (<i>n</i> = 300). Data are presented as the means ± SEM.</p

Nps1 physically interacts with Hap4.

<p><b>(A)</b><i>nps1-13</i> mutation does not affect Hap4 expression. <i>HAP4-HA</i> (BYI-19) and <i>nps1-13 HAP4-HA</i> (BYI-21) cells were grown to log phase in YPEG or YPL medium for the times indicated in the figure, after which whole-cell extracts were prepared. Proteins in the extract were separated by SDS-PAGE, and Hap4-HA was detected by immunoblotting. The densities of immunoblot bands labeled with anti-HA were normalized to those labeled with anti-Cdc28 and indicated as a bar graph of values relative to the value of WT cells grown for 0 h in YPD, which was set at “1”. Data are presented as the means ± SEM (<i>n</i> = 3). <b>(B)</b> Nps1-TAP physically interacts with Hap4-HA. BYI-20 (<i>NPS1-TAP-KanMX4 HAP4-6HA</i>::<i>URA3</i>) cells were grown to log phase in YPD medium and subsequently shifted to YPEG medium, where they were maintained for 3 h. Immunoprecipitates prepared from cell lysates with anti-HA antibody were subjected to immunoblotting with anti-TAP and anti-HA antibodies. The densities of immunoblot bands stained with anti-TAP in lanes 2 and 3 were normalized with those of bands stained with anti-HA and indicated as a bar graph of values relative to the value of YPD, which was set at “1”. Data are presented as the means ± SEM (<i>n</i> = 3).</p

RSC Chromatin-Remodeling Complex Is Important for Mitochondrial Function in <i>Saccharomyces cerevisiae</i>

<div><p>RSC (<u>R</u>emodel the <u>S</u>tructure of <u>C</u>hromatin) is an ATP-dependent chromatin remodeling complex essential for the growth of <i>Saccharomyces cerevisiae</i>. RSC exists as two distinct isoforms that share core subunits including the ATPase subunit Nps1/Sth1 but contain either Rsc1or Rsc2. Using the synthetic genetic array (SGA) of the non-essential null mutation method, we screened for mutations exhibiting synthetic growth defects in combination with the temperature-sensitive mutant, <i>nps1-105</i>, and found connections between mitochondrial function and RSC. <i>rsc</i> mutants, including <i>rsc1Δ</i>, <i>rsc2Δ</i>, and <i>nps1-13</i>, another temperature-sensitive <i>nps1</i> mutant, exhibited defective respiratory growth; in addition, <i>rsc2Δ</i> and <i>nps1-13</i> contained aggregated mitochondria. The <i>rsc2Δ</i> phenotypes were relieved by <i>RSC1</i> overexpression, indicating that the isoforms play a redundant role in respiratory growth. Genome-wide expression analysis in <i>nps1-13</i> under respiratory conditions suggested that RSC regulates the transcription of some target genes of the HAP complex, a transcriptional activator of respiratory gene expression. Nps1 physically interacted with Hap4, the transcriptional activator moiety of the HAP complex, and overexpression of <i>HAP4</i> alleviated respiratory defects in <i>nps1-13</i>, suggesting that RSC plays pivotal roles in mitochondrial gene expression and shares a set of target genes with the HAP complex.</p></div

Overexpression of <i>HAP4</i> alleviated the respiratory defect of <i>nps1-13</i>.

<p><b>(A)</b> Effect of <i>HAP4</i> overexpression on <i>nps1-13</i> growth on YPEG. WT (BY4743) and <i>nps1-13</i> (BYI-3) cells harboring pRS426 (WT/v and <i>nps1-13</i>/v, respectively) or pRS426<i>GPDpr</i>::<i>HAP4</i> (WT/<i>HAP4</i> and <i>nps1-13/HAP4</i>, respectively) were grown to log phase in SD-Ura medium, spotted on YPD and YPEG plates in serial five-fold dilutions and incubated at 30°C for 3 days. <b>(B)</b> Effect of <i>HAP4</i> overexpression on petit <i>nps1-13</i> colony formation. The strains described in <b>(A)</b> were plated on YPEG; three independent colonies were subsequently picked, pre-cultured in SD-Ura medium, and separately grown in YPD medium. On the indicated days, 200 cells from each culture were plated on YPD plates and incubated at 30°C for 3 days. Data are presented as the means ± SEM (<i>n</i> = 3).</p