Jay Mortenson - Academia.edu (original) (raw)

Papers by Jay Mortenson

S>A description is given concerning experiments to provide nuclear ; design information for th... more S>A description is given concerning experiments to provide nuclear ; design information for the NS Savannah propulsion system. Experiments were run ; on a variety of core configurations and conditions which approximated the refer-; ence core in most cases. Included are sections on facilities and equipment, ; fuel, designation of cores, critical configurations, thermal disadvantage factor, ; control rod calculations,

An experimental program for monitoring the short-term distribution and concentration of chemicall... more An experimental program for monitoring the short-term distribution and concentration of chemically dispersed oil slicks has been developed for Clean Bay, the San Francisco area oil spill cleanup cooperative. The methods used in the program are experimental and still under development. The objectives of the program are to (1) document the surface area and volume of water affected by dispersed

Journal of Zoo and Wildlife Medicine

Carfentanil citrate was given orally to five adult brown bears (Ursus arctos) on 14 separate occa... more Carfentanil citrate was given orally to five adult brown bears (Ursus arctos) on 14 separate occasions during the winter and summer to determine effective anesthetic dosages and how season may alter these dosages. Lower blood urea nitrogen:creatinine ratios, depressed appetite, and decreased activity levels in the winter versus summer were reflective of different metabolic states, even though bears were not hibernating in the winter. Doses of carfentanil citrate between 6.0 and 15.2 microg/kg were mixed with 5-10 ml of honey, which the bears licked voluntarily from a spoon. During each anesthetization, respiratory and heart rates, hemoglobin saturation, temperature, electrocardiogram, blood gas values, and level of consciousness were monitored and utilized to determine effective dosages. Mean (+/- SE) dose requirements in the winter were 7.6 +/- 0.4 microg/kg, whereas a greater mean dose of 12.7 +/- 0.5 microg/kg was required in the summer (P < 0.05). After ingestion began, stern...

The Journal of biological chemistry, Jan 10, 1969

American journal of clinical pathology, 1985

A total of 212 sera were assayed for antibody specific for cytomegalovirus by complement fixation... more A total of 212 sera were assayed for antibody specific for cytomegalovirus by complement fixation (CF), indirect immunofluorescence (IFA Electro-Nucleonics Laboratory, Inc., Bethesda, MD), ELISA (Cordis Laboratories, Inc., Miami, FL) and the FIAX system (International Diagnostic Technology, Santa Clara, CA). Correlation of CF with IFA, ELISA, and FIAX was 61%, 78%, and 71%, respectively. Quantitative correlation between IFA and FIAX and ELISA was not possible because of the broad range of reaction intensity of the latter two tests in sera with a particular IFA titer.

Encyclopedia of Women in Today's World, 2011

Encyclopedia of Women in Today's World, 2011

Experimental data are tabulated as obtained from comparative ; measurements using fuel rods provi... more Experimental data are tabulated as obtained from comparative ; measurements using fuel rods provided by the General Electric Company together ; with The Babcock and Wilcox MARTY pins. Both sets of fuel elements were clad ; with stainless steel and contained uranium dioxide enriched to 4% U-235. The ; results provide critical configurations and data for determining reactivity ; effects

International Oil Spill Conference Proceedings, 1989

A spill of approximately 9,400 bbl of San Joaquin Valley crude oil (13.5 API gravity) occurred on... more A spill of approximately 9,400 bbl of San Joaquin Valley crude oil (13.5 API gravity) occurred on April 23, 1988, from the Shell Oil Company Martinez Manufacturing Complex. Part of the high-viscosity oil eventually reached Carquinez Strait and Suisun Bay. Areas initially affected by the spill included a 103-acre freshwater marsh, the shorelines of Carquinez Strait and Suisun Bay, saltwater marshes associated with both the strait and the bay, three marinas, two local parks, and waterfront properties in Benicia. To aid in the cleanup, Shell used the facilities of the local oil spill cooperative, Clean Bay, Inc., four oil spill contractors, and U.S. Navy skimmers. Two local organizations were actively involved in caring for birds and other widlife oiled by the spill. Within four weeks, over 90 percent of the spilled oil was judged by the federal On-Scene Coordinator to have been recovered. Cleanup of floating oil involved use of skimmers and vacuum trucks. Sorbent materials were used e...

Molecular and Cellular Biology, 2014

14-3-3ζ promotes cell survival via dynamic interactions with a vast network of binding partners, ... more 14-3-3ζ promotes cell survival via dynamic interactions with a vast network of binding partners, many of which are involved in stress regulation. We show here that hypoxia (low glucose and oxygen) triggers a rearrangement of the 14-3-3ζ interactome to favor an interaction with the core autophagy regulator Atg9A. Our data suggest that the localization of mammalian Atg9A to autophagosomes requires phosphorylation on the C terminus of Atg9A at S761, which creates a 14-3-3ζ docking site. Under basal conditions, this phosphorylation is maintained at a low level and is dependent on both ULK1 and AMPK. However, upon induction of hypoxic stress, activated AMPK bypasses the requirement for ULK1 and mediates S761 phosphorylation directly, resulting in an increase in 14-3-3ζ interactions, recruitment of Atg9A to LC3-positive autophagosomes, and enhanced autophagosome production. These data suggest a novel mechanism whereby the level of autophagy induction can be modulated by AMPK/ULK1-mediated...

Cancer Research, 2013

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Breast tumors often p... more Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Breast tumors often possess regions of hypoxia in which tumor cells must either adapt metabolically to survive or die. Some tumor cells adapt and, through a process that is poorly understood, become chemoresistant. We are interested in defining the mechanisms by which this chemoresistance develops, with focus on the role of lysine acetylation_an enigmatic protein modification thought to play a role in tuning metabolism to the available nutrient supply. We posit that changes in lysine acetylation reflect metabolic adaptation to hypoxia and modulate apoptotic-signaling pathways. The importance of protein lysine acetylation in tumor cell death is evidenced by numerous clinical cancer trials testing the tumor-killing potential of deacetylase inhibitors (e.g., Varinostat). However, the molecular mechanisms by which lysine acetylation modulates cell death are poorly understood. Using a proteomics approach to characterize acetylation dynamics under conditions of hypoxic stress in breast cancer cells, we found a striking correlation between changes in acetylation and hypoxia sensitivity. Specifically, proteome-wide increases in protein acetylation were only observed in hypoxia-sensitive cell lines, likely reflecting their attempt to adapt metabolically to hypoxia. Moreover, these experiments revealed potential networks of acetylated proteins involved in the hypoxia response, including metabolic enzymes, oncogenes (e.g., c-myc), nutrient-responsive transcription factors, and 14-3-3ζ. Our previously published data suggested that acetylation of 14-3-3ζ, a small pro-survival phospho-binding protein, led to its release from protein complexes and consequently sensitized cells to apoptosis (1). Consistent with this idea, we observed a 12-fold hypoxia-induced increase in 14-3-3ζ acetylation in the hypoxia-sensitive cells (with no detectable change in 14-3-3ζ acetylation in resistant cells). Moreover, this acetylation correlated with a shift of 14-3-3ζ from high to low molecular weight gel filtration fractions, indicating a dissociation of 14-3-3ζ from protein complexes. Proteomics efforts to characterize the 14-3-3ζ interactome in sensitive cells revealed that hypoxia triggers the release of 14-3-3ζ from proteins involved in glucose metabolism, and shifts its binding to proteins involved in autophagy and starvation metabolism, implicating 14-3-3ζ as a regulator of metabolism under these conditions. Importantly, depletion of 14-3-3ζ with siRNA (thus perturbing its network of interactions) potently sensitized all breast cancer cell lines, including the most highly resistant cells, to hypoxia. Collectively, our data suggest that lysine acetylation plays an integral part in dictating the survival of cells in hypoxia. Moreover, we propose that 14-3-3ζ, and the pathways that govern its acetylation, are promising therapeutic targets to sensitize breast cancer cells to death. Citation Format: Vajira Weerasekara, Jeff Mortenson, Lisa Heppler, Joshua Lyon Andersen. Mechanisms of chemoresistance: linking lysine acetylation to cell death. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 521. doi:10.1158/1538-7445.AM2013-521

Cancer Research, 2013

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC For many cancer patie... more Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC For many cancer patients, cytotoxic chemotherapy is the primary treatment option. While the goal of these treatments is to induce tumor cell apoptosis, treatments too often fail as tumor cells possess the dynamic ability to subvert cell death and become chemoresistant. We are interested in determining the mechanisms by which tumors develop chemoresistance, with the goal of identifying potential therapeutic targets/pathways to increase the efficacy of chemotherapy. One context in which tumor cells are though to gain.14-3-3ζ is a small acidic protein that binds to phospho-serine proteins. 14-3-3ζ binding can have wide ranging effects, from the activation of enzyme function, to the orchestration of protein-protein interactions. 14-3-3ζ is highly expressed in many cancer types, and high levels of expression have been shown to correlate with the aggressiveness of tumors and lower rates of patient survival ([1][1]). However, the mechanisms by which 14-3-3ζ may promote tumor growth/tumor cell survival have yet to be determined. In this study we show that siRNA-mediated depletion of 14-3-3ζ potently sensitizes breast tumor cells to apoptosis induced by metabolic stress (e.g., hypoxia and glucose withdrawal_stresses commonly found within solid tumors) and chemotherapy. Moreover, gel filtration data suggest that metabolic cell stress induces a shift in 14-3-3ζ from high to lower molecular weight protein complexes. Drawing from these data, we performed a proteomics experiment to characterize 14-3-3ζ interactors under these conditions. We found that 14-3-3ζ associates with numerous pro-glycolysis- and cell growth-regulating enzymes (several of which are novel 14-3-3ζ interactors), and under conditions of metabolic stress, many of these interactions are diminished or lost. We are currently examining the functional consequences of these dynamic 14-3-3z interactions with respect to tumor cell survival. Together, our data suggest that 14-3-3ζ may play an apical role in regulating the metabolic response to stress, and provide insight into the mechanism by which 14-3-3ζ promotes tumor growth and survival. Citation Format: Vajira K. Weerasekara, Jeffrey B. Mortenson, Joshua L. Andersen. 14-3-3z-mediated suppression of tumor cell death. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 851. doi:10.1158/1538-7445.AM2013-851 [1]: #ref-1

Cancer Research, 2013

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Several lines of evid... more Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Several lines of evidence suggest that protein lysine acetylation pathways are deregulated in cancer ([1][1]). Moreover, deacetylase inhibitors are emerging as important anti-tumor therapeutics, suggesting that the forced reprogramming of protein-lysine acetylation is toxic to tumor cells. In this study we show that Sirt1, an NAD+-dependent Sirtuin deacetylase that promotes cancer cell survival, is aberrantly mislocalized to the cytoplasm of breast tumor cells. Moreover, the depletion of cytosolic Sirt1 by siRNA sensitizes breast tumor cells to paclitaxel-induced death. Previously, we developed a biotin-switch proteomics approach to identify cytosolic Sirt1 substrates ([2][2]). This approach yielded a variety of substrates with roles in metabolism, survival, and oxidative stress signaling. Our current work focuses on three of the proteins identified as Sirt1 substrates: SOD1, DJ-1, and 14-3-3z. SOD1 and DJ-1 both suppress oxidative stress-induced death, and high levels of 14-3-3z expression suppress chemotherapy-induced apoptosis and correlate with negative patient outcomes in breast cancer. Our preliminary results suggest that acetylation of DJ-1 and SOD1 suppress their anti-oxidant functions, while acetylation of 14-3-3z disrupts its binding to pro-survival proteins. Taken together, our data support a model in which cytosolic Sirt1 activates multiple pathways that work together to promote tumor cell survival. Citation Format: Jeffrey B. Mortenson, Vajira K. Weerasekara, Josh Andersen. Sirt1-mediated suppression of cell death in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 850. doi:10.1158/1538-7445.AM2013-850 [1]: #ref-1 [2]: #ref-2

... Bjorklund, Gary Born, Anthony Cole, Nathan Cortez, Jo Ann Davis, Matt Diller, David Driesen, ... more ... Bjorklund, Gary Born, Anthony Cole, Nathan Cortez, Jo Ann Davis, Matt Diller, David Driesen, Gráinne de Búrca, Nora Freeman Engstrom, Paolo Galizzi, Monica Hakimi, Scott Hemphill, Thomas Lee, Maggie Lemos, Benjamin Mizer, Lindsey Young Mortenson, Peter Mortenson ...

Soil Science Society of America Journal, 1967

Soil polysaccharides from the Brookston soil were extracted with hot water and purified by precip... more Soil polysaccharides from the Brookston soil were extracted with hot water and purified by precipitation, dialysis, and de⁻ proteinization with chloroform. The purified polysaccharides were fractionated on a column of diethyaminoethyl-cellulose by elution with phosphate buffers and an increasing gradient of NaOH concentration. The five fractions obtained could not be distinguished on the basis of their monosaccharide composition. Differences could be detected in the nitrogen and uronic acid contents and the electrophoretic mobility of the five fractions. The electrophoretic mobility as determined by free-boundary electrophoresis could be related to the uronic acid content of each fraction. The electrophoretic patterns indicated that all five fractions were still not homogeneous preparations.

S>A description is given concerning experiments to provide nuclear ; design information for th... more S>A description is given concerning experiments to provide nuclear ; design information for the NS Savannah propulsion system. Experiments were run ; on a variety of core configurations and conditions which approximated the refer-; ence core in most cases. Included are sections on facilities and equipment, ; fuel, designation of cores, critical configurations, thermal disadvantage factor, ; control rod calculations,

An experimental program for monitoring the short-term distribution and concentration of chemicall... more An experimental program for monitoring the short-term distribution and concentration of chemically dispersed oil slicks has been developed for Clean Bay, the San Francisco area oil spill cleanup cooperative. The methods used in the program are experimental and still under development. The objectives of the program are to (1) document the surface area and volume of water affected by dispersed

Journal of Zoo and Wildlife Medicine

Carfentanil citrate was given orally to five adult brown bears (Ursus arctos) on 14 separate occa... more Carfentanil citrate was given orally to five adult brown bears (Ursus arctos) on 14 separate occasions during the winter and summer to determine effective anesthetic dosages and how season may alter these dosages. Lower blood urea nitrogen:creatinine ratios, depressed appetite, and decreased activity levels in the winter versus summer were reflective of different metabolic states, even though bears were not hibernating in the winter. Doses of carfentanil citrate between 6.0 and 15.2 microg/kg were mixed with 5-10 ml of honey, which the bears licked voluntarily from a spoon. During each anesthetization, respiratory and heart rates, hemoglobin saturation, temperature, electrocardiogram, blood gas values, and level of consciousness were monitored and utilized to determine effective dosages. Mean (+/- SE) dose requirements in the winter were 7.6 +/- 0.4 microg/kg, whereas a greater mean dose of 12.7 +/- 0.5 microg/kg was required in the summer (P < 0.05). After ingestion began, stern...

The Journal of biological chemistry, Jan 10, 1969

American journal of clinical pathology, 1985

A total of 212 sera were assayed for antibody specific for cytomegalovirus by complement fixation... more A total of 212 sera were assayed for antibody specific for cytomegalovirus by complement fixation (CF), indirect immunofluorescence (IFA Electro-Nucleonics Laboratory, Inc., Bethesda, MD), ELISA (Cordis Laboratories, Inc., Miami, FL) and the FIAX system (International Diagnostic Technology, Santa Clara, CA). Correlation of CF with IFA, ELISA, and FIAX was 61%, 78%, and 71%, respectively. Quantitative correlation between IFA and FIAX and ELISA was not possible because of the broad range of reaction intensity of the latter two tests in sera with a particular IFA titer.

Encyclopedia of Women in Today's World, 2011

Encyclopedia of Women in Today's World, 2011

Experimental data are tabulated as obtained from comparative ; measurements using fuel rods provi... more Experimental data are tabulated as obtained from comparative ; measurements using fuel rods provided by the General Electric Company together ; with The Babcock and Wilcox MARTY pins. Both sets of fuel elements were clad ; with stainless steel and contained uranium dioxide enriched to 4% U-235. The ; results provide critical configurations and data for determining reactivity ; effects

International Oil Spill Conference Proceedings, 1989

A spill of approximately 9,400 bbl of San Joaquin Valley crude oil (13.5 API gravity) occurred on... more A spill of approximately 9,400 bbl of San Joaquin Valley crude oil (13.5 API gravity) occurred on April 23, 1988, from the Shell Oil Company Martinez Manufacturing Complex. Part of the high-viscosity oil eventually reached Carquinez Strait and Suisun Bay. Areas initially affected by the spill included a 103-acre freshwater marsh, the shorelines of Carquinez Strait and Suisun Bay, saltwater marshes associated with both the strait and the bay, three marinas, two local parks, and waterfront properties in Benicia. To aid in the cleanup, Shell used the facilities of the local oil spill cooperative, Clean Bay, Inc., four oil spill contractors, and U.S. Navy skimmers. Two local organizations were actively involved in caring for birds and other widlife oiled by the spill. Within four weeks, over 90 percent of the spilled oil was judged by the federal On-Scene Coordinator to have been recovered. Cleanup of floating oil involved use of skimmers and vacuum trucks. Sorbent materials were used e...

Molecular and Cellular Biology, 2014

14-3-3ζ promotes cell survival via dynamic interactions with a vast network of binding partners, ... more 14-3-3ζ promotes cell survival via dynamic interactions with a vast network of binding partners, many of which are involved in stress regulation. We show here that hypoxia (low glucose and oxygen) triggers a rearrangement of the 14-3-3ζ interactome to favor an interaction with the core autophagy regulator Atg9A. Our data suggest that the localization of mammalian Atg9A to autophagosomes requires phosphorylation on the C terminus of Atg9A at S761, which creates a 14-3-3ζ docking site. Under basal conditions, this phosphorylation is maintained at a low level and is dependent on both ULK1 and AMPK. However, upon induction of hypoxic stress, activated AMPK bypasses the requirement for ULK1 and mediates S761 phosphorylation directly, resulting in an increase in 14-3-3ζ interactions, recruitment of Atg9A to LC3-positive autophagosomes, and enhanced autophagosome production. These data suggest a novel mechanism whereby the level of autophagy induction can be modulated by AMPK/ULK1-mediated...

Cancer Research, 2013

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Breast tumors often p... more Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Breast tumors often possess regions of hypoxia in which tumor cells must either adapt metabolically to survive or die. Some tumor cells adapt and, through a process that is poorly understood, become chemoresistant. We are interested in defining the mechanisms by which this chemoresistance develops, with focus on the role of lysine acetylation_an enigmatic protein modification thought to play a role in tuning metabolism to the available nutrient supply. We posit that changes in lysine acetylation reflect metabolic adaptation to hypoxia and modulate apoptotic-signaling pathways. The importance of protein lysine acetylation in tumor cell death is evidenced by numerous clinical cancer trials testing the tumor-killing potential of deacetylase inhibitors (e.g., Varinostat). However, the molecular mechanisms by which lysine acetylation modulates cell death are poorly understood. Using a proteomics approach to characterize acetylation dynamics under conditions of hypoxic stress in breast cancer cells, we found a striking correlation between changes in acetylation and hypoxia sensitivity. Specifically, proteome-wide increases in protein acetylation were only observed in hypoxia-sensitive cell lines, likely reflecting their attempt to adapt metabolically to hypoxia. Moreover, these experiments revealed potential networks of acetylated proteins involved in the hypoxia response, including metabolic enzymes, oncogenes (e.g., c-myc), nutrient-responsive transcription factors, and 14-3-3ζ. Our previously published data suggested that acetylation of 14-3-3ζ, a small pro-survival phospho-binding protein, led to its release from protein complexes and consequently sensitized cells to apoptosis (1). Consistent with this idea, we observed a 12-fold hypoxia-induced increase in 14-3-3ζ acetylation in the hypoxia-sensitive cells (with no detectable change in 14-3-3ζ acetylation in resistant cells). Moreover, this acetylation correlated with a shift of 14-3-3ζ from high to low molecular weight gel filtration fractions, indicating a dissociation of 14-3-3ζ from protein complexes. Proteomics efforts to characterize the 14-3-3ζ interactome in sensitive cells revealed that hypoxia triggers the release of 14-3-3ζ from proteins involved in glucose metabolism, and shifts its binding to proteins involved in autophagy and starvation metabolism, implicating 14-3-3ζ as a regulator of metabolism under these conditions. Importantly, depletion of 14-3-3ζ with siRNA (thus perturbing its network of interactions) potently sensitized all breast cancer cell lines, including the most highly resistant cells, to hypoxia. Collectively, our data suggest that lysine acetylation plays an integral part in dictating the survival of cells in hypoxia. Moreover, we propose that 14-3-3ζ, and the pathways that govern its acetylation, are promising therapeutic targets to sensitize breast cancer cells to death. Citation Format: Vajira Weerasekara, Jeff Mortenson, Lisa Heppler, Joshua Lyon Andersen. Mechanisms of chemoresistance: linking lysine acetylation to cell death. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 521. doi:10.1158/1538-7445.AM2013-521

Cancer Research, 2013

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC For many cancer patie... more Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC For many cancer patients, cytotoxic chemotherapy is the primary treatment option. While the goal of these treatments is to induce tumor cell apoptosis, treatments too often fail as tumor cells possess the dynamic ability to subvert cell death and become chemoresistant. We are interested in determining the mechanisms by which tumors develop chemoresistance, with the goal of identifying potential therapeutic targets/pathways to increase the efficacy of chemotherapy. One context in which tumor cells are though to gain.14-3-3ζ is a small acidic protein that binds to phospho-serine proteins. 14-3-3ζ binding can have wide ranging effects, from the activation of enzyme function, to the orchestration of protein-protein interactions. 14-3-3ζ is highly expressed in many cancer types, and high levels of expression have been shown to correlate with the aggressiveness of tumors and lower rates of patient survival ([1][1]). However, the mechanisms by which 14-3-3ζ may promote tumor growth/tumor cell survival have yet to be determined. In this study we show that siRNA-mediated depletion of 14-3-3ζ potently sensitizes breast tumor cells to apoptosis induced by metabolic stress (e.g., hypoxia and glucose withdrawal_stresses commonly found within solid tumors) and chemotherapy. Moreover, gel filtration data suggest that metabolic cell stress induces a shift in 14-3-3ζ from high to lower molecular weight protein complexes. Drawing from these data, we performed a proteomics experiment to characterize 14-3-3ζ interactors under these conditions. We found that 14-3-3ζ associates with numerous pro-glycolysis- and cell growth-regulating enzymes (several of which are novel 14-3-3ζ interactors), and under conditions of metabolic stress, many of these interactions are diminished or lost. We are currently examining the functional consequences of these dynamic 14-3-3z interactions with respect to tumor cell survival. Together, our data suggest that 14-3-3ζ may play an apical role in regulating the metabolic response to stress, and provide insight into the mechanism by which 14-3-3ζ promotes tumor growth and survival. Citation Format: Vajira K. Weerasekara, Jeffrey B. Mortenson, Joshua L. Andersen. 14-3-3z-mediated suppression of tumor cell death. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 851. doi:10.1158/1538-7445.AM2013-851 [1]: #ref-1

Cancer Research, 2013

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Several lines of evid... more Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Several lines of evidence suggest that protein lysine acetylation pathways are deregulated in cancer ([1][1]). Moreover, deacetylase inhibitors are emerging as important anti-tumor therapeutics, suggesting that the forced reprogramming of protein-lysine acetylation is toxic to tumor cells. In this study we show that Sirt1, an NAD+-dependent Sirtuin deacetylase that promotes cancer cell survival, is aberrantly mislocalized to the cytoplasm of breast tumor cells. Moreover, the depletion of cytosolic Sirt1 by siRNA sensitizes breast tumor cells to paclitaxel-induced death. Previously, we developed a biotin-switch proteomics approach to identify cytosolic Sirt1 substrates ([2][2]). This approach yielded a variety of substrates with roles in metabolism, survival, and oxidative stress signaling. Our current work focuses on three of the proteins identified as Sirt1 substrates: SOD1, DJ-1, and 14-3-3z. SOD1 and DJ-1 both suppress oxidative stress-induced death, and high levels of 14-3-3z expression suppress chemotherapy-induced apoptosis and correlate with negative patient outcomes in breast cancer. Our preliminary results suggest that acetylation of DJ-1 and SOD1 suppress their anti-oxidant functions, while acetylation of 14-3-3z disrupts its binding to pro-survival proteins. Taken together, our data support a model in which cytosolic Sirt1 activates multiple pathways that work together to promote tumor cell survival. Citation Format: Jeffrey B. Mortenson, Vajira K. Weerasekara, Josh Andersen. Sirt1-mediated suppression of cell death in breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 850. doi:10.1158/1538-7445.AM2013-850 [1]: #ref-1 [2]: #ref-2

... Bjorklund, Gary Born, Anthony Cole, Nathan Cortez, Jo Ann Davis, Matt Diller, David Driesen, ... more ... Bjorklund, Gary Born, Anthony Cole, Nathan Cortez, Jo Ann Davis, Matt Diller, David Driesen, Gráinne de Búrca, Nora Freeman Engstrom, Paolo Galizzi, Monica Hakimi, Scott Hemphill, Thomas Lee, Maggie Lemos, Benjamin Mizer, Lindsey Young Mortenson, Peter Mortenson ...

Soil Science Society of America Journal, 1967

Soil polysaccharides from the Brookston soil were extracted with hot water and purified by precip... more Soil polysaccharides from the Brookston soil were extracted with hot water and purified by precipitation, dialysis, and de⁻ proteinization with chloroform. The purified polysaccharides were fractionated on a column of diethyaminoethyl-cellulose by elution with phosphate buffers and an increasing gradient of NaOH concentration. The five fractions obtained could not be distinguished on the basis of their monosaccharide composition. Differences could be detected in the nitrogen and uronic acid contents and the electrophoretic mobility of the five fractions. The electrophoretic mobility as determined by free-boundary electrophoresis could be related to the uronic acid content of each fraction. The electrophoretic patterns indicated that all five fractions were still not homogeneous preparations.