Data_Sheet_1_Exploring cell cycle-mediated regulations of glycolysis in budding yeast.pdf

Coordination of cell cycle with metabolism exists in all cell types that grow by division. It serves to build a new cell, (i) fueling building blocks for the synthesis of proteins, nucleic acids, and membranes, and (ii) producing energy through glycolysis. Cyclin-dependent kinases (Cdks) play an essential role in this coordination, thereby in the regulation of cell division. Cdks are functional homologs across eukaryotes and are the engines that drive cell cycle events and the clocks that time them. Their function is counteracted by stoichiometric inhibitors; specifically, inhibitors of cyclin-cyclin dependent kinase (cyclin/Cdk) complexes allow for their activity at specific times. Here, we provide a new perspective about the yet unknown cell cycle mechanisms impacting on metabolism. We first investigated the effect of the mitotic cyclin/Cdk1 complex Cyclin B/Cdk1—functional homolog in mammalian cells of the budding yeast Clb2/Cdk1—on yeast metabolic enzymes of, or related to, the glycolysis pathway. Six glycolytic enzymes (Glk1, Hxk2, Pgi1, Fba1, Tdh1, and Pgk1) were subjected to in vitro Cdk-mediated phosphorylation assays. Glucose-6-phosphate dehydrogenase (Zwf1), the first enzyme in the pentose phosphate pathway that is important for NADPH production, and 6-phospho-fructo-2-kinase (Pfk27), which catalyzes fructose-2,6-bisphosphate synthesis, a key regulator of glycolysis, were also included in the study. We found that, among these metabolic enzymes, Fba1 and Pgk1 may be phosphorylated by Cdk1, in addition to the known Cdk1-mediated phosphorylation of Gph1. We then investigated the possible effect of Sic1, stoichiometric inhibitor of mitotic cyclin/Cdk1 complexes in budding yeast, on the activities of three most relevant glycolytic enzymes: Hxk2, Glk1, and Tdh1. We found that Sic1 may have a negative effect on Hxk2. Altogether, we reveal possible new routes, to be further explored, through which cell cycle may regulate cellular metabolism. Because of the functional homology of cyclin/Cdk complexes and their stoichiometric inhibitors across evolution, our findings may be relevant for the regulation of cell division in eukaryotes.</p

Association between <i>MTHFD1</i> G1958A Polymorphism and Neural Tube Defects Susceptibility: A Meta-Analysis

<div><p>Objectives</p><p>The methylenetetrahydrofolate dehydrogenase (<i>MTHFD1</i>) gene, as one of the key genes involved in the folate pathway, has been reported to play a critical role in the pathogenesis of neural tube defects (NTDs). However, the results of published studies are contradictory and inconclusive. Thus, this meta-analysis aimed to evaluate the effect of the common polymorphism in the <i>MTHFD1</i> gene, the G1958A (R653Q, dbSNP ID: rs2236225) variant, on the risk of NTDs in all eligible studies.</p><p>Methods</p><p>Relevant literature published before January 3, 2014 was retrieved from the MEDLINE, EMBASE, Cochrane Library, and CBM databases. Pooled crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between the <i>MTHFD1</i> G1958A polymorphism and NTDs risk.</p><p>Results</p><p>We performed a meta-analysis of nine studies with a total of 4,302 NTDs patients and 4,238 healthy controls. Our results demonstrated a significant correlation between the <i>MTHFD1</i> G1958A polymorphism and NTDs in an overall meta-analysis. For family-based studies, the study subjects were classified as NTD cases, mothers with NTDs offspring, and fathers with NTDs offspring. We found no association between any of the fathers’ genotypes and NTDs, whereas there was a clear excess of the 1958A allele in the mothers of children with NTDs compared with controls individuals.</p><p>Conclusions</p><p>In summary, our meta-analysis strongly suggests that the <i>MTHFD1</i> G1958A polymorphism might be associated with maternal risk for NTDs in Caucasian populations. However, the evidence of this association should be interpreted with caution due to the selective nature of publication of genetic association studies.</p></div

Summary ors of the association between <i>MTHFD1</i> G1958A polymorphism and risk for NTDs.

<p>OR, odd ratio; CI; confidence interval.</p

Flow diagram of studies with specific reasons for inclusion/exclusion in the present meta-analysis.

<p>Flow diagram of studies with specific reasons for inclusion/exclusion in the present meta-analysis.</p

Forest plots of ORs for the association between the <i>MTHFD1</i> G1958A polymorphism and susceptibility to NTDs in family-based studies for each subgroup under (A: A allele vs. G allele; B: AA vs. AG+GG; C: AA vs. GG; D: AA vs. AG).

<p>Forest plots of ORs for the association between the <i>MTHFD1</i> G1958A polymorphism and susceptibility to NTDs in family-based studies for each subgroup under (A: A allele vs. G allele; B: AA vs. AG+GG; C: AA vs. GG; D: AA vs. AG).</p

Forest plots of ORs for the association between the <i>MTHFD1</i> G1958A polymorphism and susceptibility to NTDs (A: A allele vs. G allele; B: AA vs. AG+GG; C: AA vs. GG; D: AA vs. AG).

<p>Forest plots of ORs for the association between the <i>MTHFD1</i> G1958A polymorphism and susceptibility to NTDs (A: A allele vs. G allele; B: AA vs. AG+GG; C: AA vs. GG; D: AA vs. AG).</p

Main characteristics of the studies included in the meta-analysis.

<p>PCR-RFLP, Polymerase chain reaction-restriction fragment length polymorphism; PCR-SSCP, PCR-single strand conformation polymorphism; NOS, Newcastle-Ottawa scale.</p

Panel 1: the CD133 antibodies stained intensely at the membrane and in the cytoplasm of cancer cells.

<p>(A): weakly positive or focally positive staining in 10% of cells; (B): moderately or strongly positive-staining involving 10% or more of the cells; (C) and (D): the staining of CD133 on the luminal surface and the basal surface of cancer cells. Panel 2: (A): cytoplasmic or nuclear expression of β-catenin was absent; (B): nuclear expression of β-catenin was less than 10% of the cancer cells; (C) and (D): widespread nuclear accumulation of β-catenin.</p

MiRNA and mRNA-Controlled Double-Cascaded Amplifying Circuit Nanosensor for Accurate Discrimination of Breast Cancers in Living Cells, Animals, and Organoids

Metastasis is the leading cause of death in patients with breast cancer. Detecting high-risk breast cancer, including micrometastasis, at an early stage is vital for customizing the right and efficient therapies. In this study, we propose an enzyme-free isothermal cascade amplification-based DNA logic circuit in situ biomineralization nanosensor, HDNAzyme@ZIF-8, for simultaneous imaging of multidimensional biomarkers in live cells. Taking miR-21 and Ki-67 mRNA as the dual detection targets achieved sensitive logic operations and molecular recognition through the cascade hybridization chain reaction and DNAzyme. The HDNAzyme@ZIF-8 nanosensor has the ability to accurately differentiate breast cancer cells and their subtypes by comparing their relative fluorescence intensities. Of note, our nanosensor can also achieve visualization within breast cancer organoids, faithfully recapitulating the functional characteristics of parental tumor. Overall, the combination of these techniques offers a universal strategy for detecting cancers with high sensitivity and holds vast potential in clinical cancer diagnosis

Ethene Hydroformylation Catalyzed by Rhodium Dispersed with Zinc or Cobalt in Silanol Nests of Dealuminated Zeolite Beta

Catalysts for hydroformylation of ethene were prepared by grafting Rh into nests of SiOZn–OH or SiOCo–OH species prepared in dealuminated BEA zeolite. X-ray absorption spectra and infrared spectra of adsorbed CO were used to characterize the dispersion of Rh. The Rh dispersion was found to increase markedly with increasing M/Rh (M = Zn or Co) ratio; further increases in Rh dispersion occurred upon use for ethene hydroformylation catalysis. The turnover frequency for ethene hydroformylation measured for a fixed set of reaction conditions increased with the fraction of atomically dispersed Rh. The ethene hydroformylation activity is 15.5-fold higher for M = Co than for M = Zn, whereas the propanal selectivity is slightly greater for the latter catalyst. The activity of the Co-containing catalyst exceeds that of all previously reported Rh-containing bimetallic catalysts. The rates of ethene hydroformylation and ethene hydrogenation exhibit positive reaction orders in ethene and hydrogen but negative orders in carbon monoxide. In situ IR spectroscopy and the kinetics of the catalytic reactions suggest that ethene hydroformylation is mainly catalyzed by atomically dispersed Rh that is influenced by Rh–M interactions, whereas ethene hydrogenation is mainly catalyzed by Rh nanoclusters. In situ IR spectroscopy also indicates that the ethene hydroformylation is rate limited by formation of propionyl groups and by their hydrogenation, a conclusion supported by the measured H/D kinetic isotope effect. This study presents a novel method for creating highly active Rh-containing bimetallic sites for ethene hydroformylation and provides new insights into the mechanism and kinetics of this process