did rockefeller found the american cancer society

Texarkana is actually two cities -- one in Texas and one in Arkansas -- divided by the Texas-Arkansas state line. John Rockefeller and modern medicine: Abraham Flexner was born in 1866 in Louisville, Kentucky. ); grants or awards from the US Department of Defense, National Cancer Institute (R01 CA236814) (DoD; CA180190), the Myeloma Crowd Research Initiative award, and the Riney Family Multiple Myeloma Research Program Fund (F.Z. Similar effects of DCA treatment were observed in other cancer types, such as non-small cell lung cancer cells38 and breast cancer cells.39 Our results indicate that the reliance of MM cells on glycolysis for proliferation and survival is not related to an intrinsic inability to perform OXPHOS because MM cells are able to switch to OXPHOS when cultured in the presence of galactose instead of glucose. Edith began support of the Art Institute in 1909 as a charter member and supported it with monetary contributions and loans from her extensive personal art collection. Experimental details are provided in the supplemental Materials and Methods. All univariate P values were reported regardless of significance. Multiple myeloma (MM) is a malignancy characterized by the clonal expansion of plasma cells in the bone marrow. [13] He was given custody of their youngest daughter Mathilde so that she could marry Max Oser, a Swiss riding instructor. "Having that many people there, it was just incredible.". Couric invited Lavender to attend the Stand Up to Cancer telethon in Los Angeles, which Couric had co-founded to raise money for cancer research. "She never wallowed in it," Kesterson says. Laurance received many honors for his efforts on behalf of the environment and cancer research and treatment. When evidence began to emerge that petroleum based medicine was causing cancer, Rockefeller founded the American Cancer Society, through which he suppressed that information. "It was a great place to grow up." It's sad to know how brainwashed breast cancer awareness is about chemotherapy, radiation, and surgery. No striking differences in the extracellular acidification rates (ECARs) or basal oxygen consumption rates (OCRs) were observed, indicating similar basal glycolysis and OXPHOS activity (Figure1A, supplemental Figure1A). SPEEDING TO ILL SISTER; Financier, Despite Attack of Shingles, Is on Way to Chicago to See Mrs. Edith McCormick", "J.D. Mathilde and Max were married in London in April 1923. (PBMNCs and purified Bcellswere obtained from 3 healthy donors). She also helped local candidates campaign, putting up yard signs and other tasks. News arrived that Edith and Harold's elder son, John Rockefeller McCormick, had died of scarlet fever. He lived until 1959. Here, we show that human MM cell lines (HMCLs) rely on glycolysis for proliferation and survival. Neither these AP materials nor any portion thereof may be stored in a computer except for personal and noncommercial use. "Betsy Lavender has been such a tireless warrior and powerful voice about the importance of early detection for colon cancer," Couric says. Glycolysis, TCA cycle, and OXPHOS gene sets significantly depleted in MK2206-treated control clones in comparison with FOXO-deficient and untreated clones (Figure3B, supplemental Figure3A-C). A local paper noted, of the first fair, that "One feature of the exhibit will be a collection of newspaper and magazine clippings, from various countries during the last 200 years emphasizing the storm of protest which greeted every suggestion for a freer social status for women. (B) Basal glycolysis in HMCLs and MMPCs (n= 2 patients) treated with 2.5 M MK2206 (blue bars) for 20 hours or untreated (red bars). Edith Rockefeller McCormick (August 31, 1872 - August 25, 1932) was an American socialite, daughter of Standard Oil co-founder John D. Rockefeller . Her friend won. LE analysis provided the genes that contributed most prominently to the core enrichment of multiple gene sets associated with glycolysis, the TCA cycle, and OXPHOS (supplemental Table1). These alterations may result in metabolic dependencies that can be exploited for therapeutic purposes. I drive everybody crazy.". As one of the wealthiest and most influential families in North America in the last 200 years, headed up by patriarch John D. Rockefeller I (pictured), the Rockefellers played an integral role in . The American Society for the Control of Cancer (the forerunner of the American Cancer Society) was established with the aid of John D. Rockefeller, and the first X-ray machine was put into use. Similar to other cancer types, MM cells predominantly fulfill their energetic demands via glycolysis,2,3 a phenomenon known as the Warburg effect.4 In agreement, it was shown that the glycolysis rate-limiting enzyme, hexokinase II (HK2), is highly expressed in MM and is associated with poor prognosis.2,5,6. Here, we demonstrate that negative regulation of the forkhead box O (FOXO) transcription factors (TFs) by AKT is crucial to prevent the metabolic shutdown in MM cells, thus contributing to their metabolic adaptability. Notably, there was no correlation between 2-DG sensitivity and metabolic function in the cell lines tested (Figure1C and supplemental Figure1C), suggesting that 2-DGdependent cell death involves a different mechanism, such as the induction of endoplasmic reticulum stress through the inhibition of N-glycosylation, as previously described.28. Correspondence: Jeroen E.J. Similarly, the expression of genes associated with most steps of the TCA cycle were downregulated (>1.2-fold) in a FOXO-dependent fashion upon AKT inhibition in at least 2 HMCLs, whereas the expression of ATP citrate lyase decreased in all 3 HMCLs (Figure3D). She and Harold, along with other wealthy patrons, founded the Grand Opera Company, the first in Chicago, in 1909. Here is a quote from John D. Rockefeller that sums up his vision for America: "I don't want a nation of thinkers. She knew something was wrong, so she planned to drive to Texarkana to see a doctor her family knew. We passed out Clinton buttons and stickers." (C) Basal respiration and spare respiratory capacity in HMCLs and MMPCs (n= 2 patients) treated with 2.5 M MK2206 (blue bars) or untreated(red bars) for 20 hours. (D) Fold change of ECAR, basal respiration, maximum respiration, and spare respiratory capacity (OCR) from a Seahorse XF mitochondrial stress test in HMCLs treated with DCA (25 mM for 20 hours) or cultured for 4 days in a galactose-containing medium (11.1 mM, no glucose). Most HMCLs show an increased expression of the MYC proto-oncogene because of chromosomal rearrangements and/or mutations.42 An aberrant MYC expression is a major determinant of the metabolic phenotype of MM cells,35 and may drive glycolysis because it directly activates the expression of almost all glycolysis genes.43 Correspondingly, the glycolytic reserve was comparably low in BLCLs that represent archetypal MYC-driven lymphomas. In this month of breast cancer awareness, it is sad to see people being brainwashed about chemotherapy, radiation and surgery. By the turn on the 20th century, he controlled 90% of all oil refineries in the U.S. through his oil company, Standard Oil, which was later on broken up to become Chevron, Exxon, Mobil etc. Her Texarkana doctor recommended that she go to UAMS in Little Rock for treatment. In February 1923, she received some minor press for claiming to be the reincarnation of the wife of King Tutankhamen, whose tomb had just been explored and was a popular topic. "I think attitude probably was most important to me," she says, adding that it is important never to give up and "to make the best of everything. (A) Kaplan-Meier univariate analysis for the OS of k-means clusteringdefined groups of patients with MM (776 patients in total). At the time of her death, her estate, through the Edith Rockefeller McCormick Trust set up by her father in 1923, consisted mostly of real estate and no longer held much Standard Oil stock. Our data suggest that repression of FOXO by AKT is essential to sustain glycolysis and the TCA cycle activity in MM cells and, as such, predicts patient survival. For Lavender, staying positive is key to dealing with cancer and all of life's challenges. Longtime friends are not surprised at Lavender's dedication to colorectal cancer awareness and prevention. Most genes involved in glycolysis and the TCA cycle significantly downregulated in a FOXO-dependent manner after AKT inhibition (Figure3C). (A) Immunoblot analysis of HK2 and PKM2 expression in LME-1, MM1.S, and XG-3 Cas9-CTRL clones CTRL and FOXO KO clones (FOXO1 for LME-1, and FOXO3 for MM1.S and XG-3) treated overnight with 2.5 M MK2206 or left untreated. 01 May 2023 02:14:13 . Upon graduation from college, Lavender moved to Little Rock to work for Alltel's wireless company in customer service. Meanwhile, Harold married Ganna Walska, a Polish opera singer in August 1922, becoming her fourth husband. She then went to UAMS, where she says the care she received saved her life. However, at high glucose uptake rates, the activation of glycolysis and decreased mitochondrial respiration results in more ATP production due to a more efficient cytoplasmic solvent capacity.40 Rapidly proliferating cells are characterized by a high glucose uptake capacity,41 which may explain the glycolytic phenotype of HMCLs. provided theoretical and technical input and supervised the metabolic profiling experiments; M.S., C.J.M.v.N., and J.E.J.G. Oftentimes, younger patients don't get timely diagnoses because doctors don't think they are old enough to have colorectal cancer, she says. He was also a "big, big" Razorback fan, she says, a passion she shares with him. "It was a fabulous environment that day," Lavender says, noting that more than 1,000 people participated in 2022. American Cancer Society - 1913 . G protein-coupled receptors (GPCRs) modulate diverse cellular signaling pathways and are important drug targets. Bair, Deirdre, "Jung - A Biography" London: Time-Warner Books UK, 2004, This page was last edited on 28 April 2023, at 05:29. To continue their mission today, Shah says the RF must "directly confront climate change". In 1913, America's first billionaire endowed the Rockefeller Foundation, which had the ambitious goal "to promote the well-being of mankind throughout the world." The foundation contributed to. (B) Multivariate analysis of subgroups (n= 525) for OS. She was the fourth daughter of schoolteacher Laura Celestia "Cettie" Spelman (18391915) and Standard Oil co-founder John Davison Rockefeller. Moreover, our results suggest that AKT signaling sustains OXPHOS independently of its effects on glycolysis because AKT inhibition still decreased mitochondrial respiration when pyruvate was present as the sole carbon source, thereby obviating the need for pyruvate provided by glycolysis. The oxidation of galactose to pyruvate by glycolysis yields no netATP, forcing cells to rely on mitochondrial respiration for ATPgeneration, which is characterized by an increased OCR (Figure1D).30,31 Galactose caused a significant decrease in the ECAR/OCR ratio in all HMCLs tested, indicating that HMCLs can switch to OXPHOS when forced to do so (Figure1E). To determine the functional metabolic features of HMCLs in comparison with other mature malignant B-cell lines (BCLs), normal activated human peripheral blood mononuclear cells (PBMNCs), and activated purified B cells, glycolysis and mitochondrial stress tests were performed. performed analyses on clinical data and gene expression datasets; R.H.H. The American Cancer Society suggests that people with average risk for colorectal cancer should get screened starting at age 45. [22], Harold McCormick and Edith Rockefeller, 1895, "MYSTERY OF CHICAGO'S 110 UNWED MILLION-HEIRESSES" Youngstown Vindicator, June 5, 1927, "MRS. M'CORMICK SAYS TUTANKHAMEN WED HER", The Hartford Courant, Mar 1, 1923. p. 22, "WOMEN TO UNITE TO DISPLAY RECORDS OF ACHIEVEMENT OF MODERN ENTERPRISE", Lawrence Daily Journal-World, Feb. 19, 1925 at p. 9, "MRS. McCORMICK'S CAREER. Seahorse extracellular flux (XF) metabolic profiling experiments were performed according to the manufacturers protocols. We have previously shown that prosurvival AKT signaling in MM critically depends on the inhibition of FOXO TFs, resulting in the stabilization of the antiapoptotic MCL-1 protein.18 Here, we show that the expression of key metabolic genes in MM is also regulated by AKT signaling that restrains FOXO-dependent gene repression. In agreement, the phosphorylation of FOXO1 (Thr24) and FOXO3 (Thr32), which mark their inactivation, followed a similar pattern (Figure1F). Its global headquarters is located in the American Cancer Society Center in Atlanta, Georgia. This study was supported by a grant from the Dutch Cancer Society (KWF) (AMC 2018-11597) (J.E.J.G. Stasz, Clarice. "My mission is to promote timely screenings," she says. FDR, ES, NES, and P-values are shown in the plots. EDITH ROCKEFELLER TO GET $8,419,032", "J.D. (B) GSEA in Cas9-CTRL HMCL clones treated overnight with 2.5 M MK2206 (CTRL+MK) vs the combination of untreated CTRL clones and FOXO KO clones, either treated overnight with 2.5 M MK2206 or left untreated (REST). (F) Immunoblot analysis of total and phosphorylated (Ser473) AKT, total and phosphorylated (Thr24) FOXO1, and total and phosphorylated (Thr32) FOXO3 in the HMCLs LME-1, LP-1, and XG-1 cells cultured for 20 hours with or without 25 mM DCA or in a galactose-containing, glucose-free medium. Patient material was obtained according to the ethical standards of our institutional medical ethical committee, as well as in agreement with the 1975 declaration of Helsinki, as revised in1983. Her brother was John Davison Rockefeller Jr. (18741960). In agreement, the glycolytic rate of primary MM cells was lower than that of HMCLs, perhaps explained by the low invitro proliferative capacity of primary cells. The first International Congress in Human Genetics to convene after WWII was held in Copenhagen in 1956. AKT inhibition suppresses glycolysis and OXPHOS in MM cells. Established in 1913, the foundation used the Rockefeller family wealth to ostensibly promote "public health" by funding mass vaccination campaigns and the founding of public health authorities around the world. "I've gotten a [regular] colonoscopy since I was 10 years old," Merritt says. She joined Chi Omega sorority and was an Associated Student Government (ASG) representative. She attributes her good outcome to the doctors, especially her surgeon, Dr. Jason Mizell, and her oncologist, Dr. Sam Makhoul (now at CARTI), nurses and other staff who helped in her recovery. Basal ECAR values from the Seahorse XF glycolysis stress test are depicted, and means SEM are shown (ttest,n=5-6 measurements). For Lavender, 52, a colorectal cancer survivor, participating is part of her mission to encourage people to get screened for colorectal cancer. NONE OF FAMILY ON SHIP $50,000 Fee Reported for Psychoanalyst Who Will See Herto Chicago Home", "MRS. H. F. M'CORMICK OBTAINS DIVORCE IN FIFTY MINUTES; John D. Rockefeller's Daughter Gains Decree for Desertion, Which Husband Admits. Multiple myeloma (MM) plasma cells show increased glycolysis and oxidative phosphorylation (OXPHOS), which are characteristics associated with recurrent genetic aberrations that drive the proliferation and survival of MM cells. GEP data were obtained using samples from patients with MM who were at baseline and were undergoing total therapy 2 (TT2) or TT3 protocols.22 The clinical course for the patients showing high expression of these FOXO-repressed metabolic genes was characterized by a highly inferior OS (P< .0001). (B) Seahorse XF glycolysis stress test profiles of CTRL clones (left panels, n= 2), and FOXO knockout clones (middle panels, n= 2) treated for 20 hours with 2.5 M MK2206 (red lines) or left untreated (blue lines). "That was a lot of fun," she says, adding that it was the first time she was involved in developing strategy for a political race. After dinner, where they met Clinton and his wife, Hillary, they got back on the charter bus and headed home. Ile Ife, Nigeria | 29 views, 5 likes, 0 loves, 0 comments, 0 shares, Facebook Watch Videos from Spokesman Sanctuary Of Hope: Join us this evening at 4:30 pm WAT onsite or online for a powerful. [11] She returned to America in 1921 after an eightyear stay. American spin-off organizations associated with these Rockefeller-supported programs include the American Eugenics Society (synonymous with Rockefeller's Population Council) and the Human Genome Project). Harold Fowler McCormick Jr. (18981973), who married Anne Urquhart Brown "Fifi" (, Muriel McCormick (19031959), who married Elisha Dyer Hubbard (1878-1936), a nephew of. Conflict-of-interest disclosure: The authors declare no competing financial interests. "It was the change and not knowing what was going to happen dealing with what was thrown at you and making the best way out of it.". provided analytical support; J.D.S., T.C.A., and F.Z. Tera Futrell Kesterson of Nashville in Howard County, who met Lavender in college as Chi Omega sorority sisters, says Lavender is a "great friend" to many and inspired others with her courage, especially during her recovery from colorectal cancer. However, this resulted in reduced proliferation and cell death in several HMCLs, suggesting that the ATP generated from mitochondrial respiration is not sufficient to meet the metabolic demands of MM cells. Protein expression of the glycolysis rate-limiting enzyme HK2 was decreased upon MK2206 treatment, whereas the effects on pyruvate kinase M2 (PKM2) were modest (Figure2A). "It's not just awareness for the patient to do their screenings," she says. They saw the sights, Lavender says, but her small crew of interns stayed busy with work. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. All flow cytometry data were obtained using a FACSCanto or LSR Fortessa (BD Biosciences, Franklin Lakes, NJ) and analyzed using FlowJo software (FlowJo, Ashland, OR). The American Cancer Society invests hundreds of millions of dollars every year to fight cancer on a global scale and has earned the public trust by demonstrating a history of careful and proven financial stewardship for over a century. (C) Seahorse XF mitochondrial stress test profiles of CTRL clones (left panels, n= 2), and FOXO KO clones (middle panels, n= 2) treated for 20 hours with 2.5 M MK2206 (blue lines) or left untreated (red lines). Groups were defined as high (red lines) or low (blue lines) expressing groups. Edith Rockefeller McCormick (August 31, 1872 August 25, 1932) was an American socialite, daughter of Standard Oil co-founder John D. Rockefeller. Bar graphs (right panels) depict basal glycolysis values, means SEM are shown (one-way ANOVA, with Bonferroni multiple comparison test). WASHINGTON A top official of the American Cancer Society has resigned in part because of concern over some of the organization's fund-raising partnerships. UAMS started the walk in 2021 to honor patients with all forms of cancer and raise money for cancer research. According to the UAMS website, the "NCI Designation is a highly competitive assessment process during which cancer centers must demonstrate outstanding depth and breadth of high-quality cancer research and treatment." Her father, on the other hand, was more serious and disciplined as he worked hard at his law practice. April 30, 2023 at 7:30 a.m. Betsy Lavender at the Winthrop Rockefeller Cancer Institute at UAMS. Upon graduation from high school, Lavender headed to the University of Arkansas at Fayetteville where she studied advertising and public relations. Although novel treatment strategies have improved the prognosis and outcome of MM, most patients eventually relapse and become refractory to further treatment. Edith was born on August 31, 1872 at her parents' home in Cleveland, Ohio. doi: https://doi.org/10.1182/bloodadvances.2022007383. They later moved to Chicago. We demonstrated that FOXO was an absolute requirement for the effects of AKT inhibition, suggesting that AKT regulates metabolism in MM, predominantly at the transcriptional level. MM cells are characterized by the high expression of lactate dehydrogenase,35-37 which catalyzes the conversion of pyruvate into lactate instead of into acetyl-CoA. "I love it to this day," she says. OCR values from the Seahorse XF mitochondrial stress test are depicted, and means SEM are shown (t-test, n= 5-6 measurements).ttest,P< .05; MMPC, primary MM plasma cells. She also took on a new role to raise awareness of colorectal cancer and promote screening for the disease. It will be her second year to participate in the walk, and she hopes to raise even more money than she did last year, when her team took top fundraising honors in the individuals category. Her three elder sisters were Elizabeth (Bessie) (18661906), Alice (18691870), and Alta (18711962). CTRL, control; ES, enrichment score; FDR, false discovery rate; KEGG, Kyoto Encyclopedia of Genes and Genomes; KO, knockout; NES, normalized enrichment score. In addition, we show that the LE glycolysis, LE TCA, and LE OXPHOS gene sets are significantly enriched in MMPCs from newly diagnosed patients (Figure5B) and patients with refractory/relapsed MM in comparison with those having healthy donor plasma cells, but not in those with monoclonal gammopathy of undetermined significance. As for cancer, oh yeah, the American Cancer Society was founded by none other than Rockefeller in 1913. She is especially interested in raising awareness of early onset colorectal cancer, which occurs in people under age 45 and is on the rise. 1 Cancer cells are characterized by metabolic alterations, which are driven by oncogenes. AKT signaling is an important driver of metabolism, either directly through the phosphorylation of key metabolic enzymes, or indirectly by controlling the expression of metabolic genes.20 The latter mainly involves the regulation of members of the FOXO TFs. For the glycolysis pathway, red, blue, and yellow symbols indicate >1.5-fold (FOXO-dependent) decrease in gene expression in LME-1, MM1.S, and XG-3, respectively. "Sometimes, I think it was better than any drug they could have given me," she says. These results indicate that AKT signaling is required to restrain the FOXO-dependent suppression of many key metabolic enzymes in MM cells. In high school, Lavender was very involved in "almost every activity," she says. By establishing the China Medical Board in 1914 and purchasing the Union Medical College from the London Missionary Society in 1915, the Foundation took its first steps toward that goal. . Lavender was 42 when she was diagnosed. -actin served as a loading control. "[17] She was also said to be interested in astrology and to celebrate Christmas on December 15. Similarly, the normalized spare respiratory capacity of HMCLs was similar to that of other BCLs, demonstrating that HMCLs and BCLs do not differ with regard to mitochondrial adaptability.27 However, both HMCLs and Burkitt lymphoma cell lines (BLCLs) showed very limited normalized glycolytic reserve (Figure1A). For the LE TCA and LE OXPHOS high groups (n= 178 and n= 170, respectively), the 5.5-year survival rate was 57% vs for the LE TCA and LE OXPHOS low groups, it was 71% (n= 598 and n= 606, respectively) (Figure5A). These effects appear to be cell/tissue contextspecific because several studies report the opposite, showing that FOXO expression is actually required for glucose metabolism and the TCA cycle in neural and intestinal stem cells.50,51 In agreement with our data, it was shown that FOXO3a antagonized MYC and repressed genes involved in the mitochondrial respiration in colon cancer cells52 and in glycolysis in melanoma cells.53. "Anything that is thrown at me doesn't rattle me.". Means SEM of OCR values are depicted (n= 5 measurements for each clone) and Seahorse XF injections are shown: oligomycin (=A), FCCP (=B), rotenone and antimycin A (=C). In addition to the walk, there will be drawings, games, entertainment and retail booths. She then traveled to Denver to work with media logistics for the Democratic National Convention. The married couple spent their first two years living in Council Bluffs, Iowa, where Harold managed a branch of his father's business. The official, Dr . "She just kept moving forward and kept educating people, and every time we have someone we know get cancer, Betsy's the first one there to guide them through that initial diagnosis.". Her father had surgery there, and the experience was good. After recovering, she moved back to Fayetteville, where she had always hoped to return, and began focusing on fundraising projects. Metabolic alterations are important cancer-associated features that allow cancer cell transformation and survival under stress conditions. -actin served as a loading control. Enzymes (purple boxes), metabolites, and conversions (arrows) are indicated. [12], Edith and Harold were divorced in December 1921. From hectic politics to the unexpected peril of colorectal cancer, Lavender just laces up her shoes and deals with whatever life throws at her. One-way ANOVA with Bonferroni multiple comparisons test P< .05, P< .01; One-sample t test P< .05, P< .01; paired t test, P< .05; ANOVA, analysis of variance; ns, not significant; SEM, standard error of the mean. And the fact that she's willing to scream it from the mountaintops makes me love her even more.". Guikema, Department of Pathology, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands; e-mail: j.e.guikema@amsterdamumc.nl. and G.H.K. Classification of patients with MM according to several metabolism-associated gene sets revealed that the FOXO-dependent repression of these genes confers a favorable prognosis. CI, confidence interval; B2M, beta2-microglobulin; Hb, hemoglobin; HR, hazard ratio; ISS, International Staging System; LDH, lactate dehydrogenase. During aerobic glycolysis, glucose is converted to pyruvate and subsequently to acetyl-CoA to fuel the TCA cycle and OXPHOS. "We got there, and it was snowing. She was born in Fayetteville in 1970 while her father, Bill Lavender, was finishing law school at the University of Arkansas. The protein kinase B/AKT acts as a central node in cellular metabolism and is constitutively active in MM cells. "We would go to different countries.". In addition, regular screening can prevent colorectal cancer by allowing doctors to find and remove polyps before they turn into cancer. and G.d.W performed the experiments and analyses; R.J.B. John D. Rockefeller is also the son of the founder of the pharmaceutical industry in the US. She was a member of both the Young Democrats group and the Teenage Republicans. It all starts with John D. Rockefeller (1839 - 1937) who was an oil magnate, a robber baron, America's first billionaire, and a natural-born monopolist. "[14] Over the next few years, Edith and Harold frequently found themselves in court in lawsuits over the divorce agreement.[15]. In agreement, we found that the FOXO-mediated repression of key metabolic genes is lost in MM plasma cells in comparison with plasma cells from healthy donors, patients with monoclonal gammopathy of undetermined significance, and patients with smoldering MM, suggesting that the progressive loss of FOXO-dependent gene regulation accompanies the malignant transformation of plasma cells. [7], In 1913, she travelled to Zurich to be treated for depression by Carl Gustav Jung, and contributed generously to the Zrich Psychological Society. To continue their mission today, Shah says the RF must "directly confront climate change". On November 26, 1895, she married Harold Fowler McCormick from Chicago, a son of Nancy Fowler and Cyrus Hall McCormick, the inventor of the mechanical reaper. She was on student council and attended Girls' State and the Governor's School, a summer program then held at Hendrix College. She was educated at home by private tutors and, unlike other women of means at the time, did not attend finishing school.[1]. I was his first wife. AKT was shown to regulate the expression of metabolic genes, primarily by controlling FOXO TFs.20,32 Previously, we defined a gene set that became repressed by FOXO upon AKT inhibition in MM cells (shared FOXOrepressed).18 GSEA indicated that the expression of these genes was enriched in MM cells (n= 75) in comparison with healthy donor plasma cells (n= 15),23 suggesting that FOXO is less active in MM cells (Figure3A). Moreover, the FOXO-dependent repression of glycolysis- and TCA-associated genes correlates with a favorable prognosis in a large cohort of patients with MM. Mean values for basal glycolysis andnormalized glycolytic reserve (percentage of basal glycolysis) based on ECAR and mean values for basal respiration and normalized spare respiratory capacity(percentage of basal respiration) based on OCR are depicted (one-way ANOVA with Bonferroni multiple comparisons test; HMCLs vs BCLs, n= 5 measurements.

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