Digital Commons Network^™

New Technologies Reduce Greenhouse Gas Emissions From Nitrogenous Fertilizer In China, Wei-Feng Feng, Zheng-Xia Dou, Pan He, Xiao-Tang Ju, David Powlson, Dave Chadwick, David Norse, Yue-Lai Lu, Ying Zhang, Liang Wu, Xin-Ping Chen, Kenneth Cassman, Fu-Suo Zhang

Department of Agronomy and Horticulture: Faculty Publications

Synthetic nitrogen (N) fertilizer has played a key role in enhancing food production and keeping half of the world’s population adequately fed. However, decades of N fertilizer overuse in many parts of the world have contributed to soil, water, and air pollution; reducing excessive N losses and emissions is a central environmental challenge in the 21st century. China’s participation is essential to global efforts in reducing N-related greenhouse gas (GHG) emissions because China is the largest producer and consumer of fertilizer N. To evaluate the impact of China’s use of N fertilizer, we quantify the carbon footprint of China’s N …

Use Of A Surrogate To Evaluate The Impact Of Tillage On The Transport Of Steroid Hormones From Manure-Amended Agricultural Fields, Sagor Biswas, William L. Kranz, Charles A. Shapiro, Mitiku Mamo, Shannon L. Bartelt-Hunt, Daniel D. Snow, David P. Shelton, David D. Tarkalson, Terry L. Mader, Simon J. Van Donk, Tian C. Zhang

Department of Agricultural and Biological Systems Engineering: Faculty Publications

Beef feedlot manure distributed to row crop production areas is a potential surface water contaminant source of the steroid hormones commonly used in beef cattle production. This article reports on research conducted at the University of Nebraska Haskell Agricultural Laboratory near Concord, Nebraska, in July 2009. Manure, collected from beef feedlot pens, was stockpiled for ten months prior to application to a row crop field. Previous research identified that the detection frequency of steroid hormones in beef manure varies greatly. Thus, a surrogate (17α-ethynylestradiol, EE2) was applied at a rate of 75 g ha^-1 to ensure detectable concentrations in …

Use Of A Surrogate To Evaluate The Impact Of Tillage On The Transport Of Steroid Hormones From Manure-Amended Agricultural Fields, Sagor Biswas, William Kranz, Charles A. Shapiro, Mitiku Mamo, Shannon L. Bartelt-Hunt, Daniel D. Snow, David P. Shelton, David D. Tarkalson, Terry L. Mader, Simon J. Van Donk, Tian C. Zhang

Department of Agricultural and Biological Systems Engineering: Faculty Publications

Beef feedlot manure distributed to row crop production areas is a potential surface water contaminant source of the steroid hormones commonly used in beef cattle production. This article reports on research conducted at the University of Nebraska Haskell Agricultural Laboratory near Concord, Nebraska, in July 2009. Manure, collected from beef feedlot pens, was stockpiled for ten months prior to application to a row crop field. Previous research identified that the detection frequency of steroid hormones in beef manure varies greatly. Thus, a surrogate (17α-ethynylestradiol, EE2) was applied at a rate of 75 g ha^-1 to ensure detectable concentrations in …

Transport Of Steroid Hormones In The Vadose Zone After Land Application Of Beef Cattle Manure, Simon Van Donk, Sagor Biswas, William L. Kranz, Daniel D. Snow, Shannon L. Bartelt-Hunt, Terry L. Mader, Charles A. Shapiro, David P. Shelton, David D. Tarkalson, Tian .. Zhang, Steve Ensley

Department of Agricultural and Biological Systems Engineering: Faculty Publications

Few studies have been conducted to investigate the potential contamination of groundwater from manureborne steroid hormones. The objective of this study was to monitor leaching of steroid hormones at the bottom of 2.4 m deep percolation lysimeters installed in plots treated with beef cattle manure. Soil samples were also collected from surrounding field plots. Treatments consisted of application of manure from two treatment methods (stockpiling and composting) or no manure application. Laboratory analyses of manure, soil, and leachate samples used liquid chromatography and tandem mass spectrometry to identify 17 steroid hormones and metabolites. Progesterone, estrone, β-zearalenol, and 4-androstenedione were detected …

Surface- And Hydrogel-Mediated Delivery Of Nucleic Acid Nanoparticles, Angela K. Pannier, Tatiana Segura

Department of Agricultural and Biological Systems Engineering: Faculty Publications

Gene expression within a cell population can be directly altered through gene delivery approaches. Traditionally for nonviral delivery, plasmids or siRNA molecules, encoding or targeting the gene of interest, are packaged within nanoparticles. These nanoparticles are then delivered to the media surrounding cells seeded onto tissue culture plastic; this technique is termed bolus delivery. Although bolus delivery is widely utilized to screen for efficient delivery vehicles and to study gene function in vitro, this delivery strategy may not result in efficient gene transfer for all cell types or may not identify those delivery vehicles that will be efficient in vivo. …

Acetyl-Coa Carboxylases Are Checkpoints In Adipocyte Differentiation, Elizabeth Lyn Cordonier, Daniel Camara Teixeira, Zhonghi Han, Angela K. Pannier, Janos Zempleni

Department of Agricultural and Biological Systems Engineering: Faculty Publications

No abstract provided.

Changing Room Cues Reduces The Effects Of Proactive Interference In Clark’S Nutcrackers, Nucifraga Columbiana, Jody L. Lewis, Alan C. Kamil, Kate E. Webbink

Avian Cognition Papers

To determine what factors are important for minimizing interference effects in spatial memory, Clark’s Nutcrackers, Nucifraga columbiana were tested for their spatial memory for two serial lists of locations per day. In this experiment two unique landmark sets were either different between List 1 and List 2 or the same. We found that Nutcrackers were most susceptible to interference when the landmark sets were the same. This study suggests that repeatedly testing animal memory in the same room, with the same cues, can hamper recall due to interference.

Functional Convergence Of Structurally Distinct Thioesterases From Cyanobacteria And Plants Involved In Phylloquinone Biosynthesis, Fabienne Furt, William J. Allen, Joshua R. Widhalm, Peter Madzelan, Robert C. Rizzo, Gilles J. Basset, Mark A. Wilson

Department of Biochemistry: Faculty Publications

The synthesis of phylloquinone (vitamin K₁) in photosynthetic organisms requires a thioesterase that hydrolyzes 1,4-dihydroxy- 2-naphthoyl-CoA (DHNA-CoA) to release 1,4- dihydroxy-2-naphthoate (DHNA). Cyanobacteria and plants contain distantly related hotdog-fold thioesterases that catalyze this reaction, although the structural basis of these convergent enzymatic activities is unknown. To investigate this, the crystal structures of hotdog-fold DHNA-CoA thioesterases from the cyanobacterium Synechocystis (Slr0204) and the flowering plant Arabidopsis thaliana (AtDHNAT1) were determined. These enzymes form distinct homotetramers and use different active sites to catalyze hydrolysis of DHNACoA, similar to the 4-hydroxybenzoyl-CoA (4-HBA-CoA) thioesterases from Pseudomonas and Arthrobacter. Like the 4-HBA-CoA …

Food Webs And Food Sovereignty: Research Agenda For Sustainability, Charles A. Francis, Michelle Miller, Molly Anderson, Nancy Creamer, Michelle Wander, Jacob Park, Thomas Green, Brent Mccown

Department of Agronomy and Horticulture: Faculty Publications

Future food production will be constrained by the scarcity of fossil fuel and fresh water as well as increasing intensity and unpredictability of weather events and climate changes. The assurance of food security and equity for many consumers is complicated by concentration of ownership of land and other production resources, as well as a global corporate food systems model that is driven by profit at the expense of people and the environment. To assess potential alternatives to the contemporary global food chain, well focused research is needed on local food production and food webs where small- and midscale family farms …

Microrna Function In Human Diseases, Sathish Kumar Natarajan, Mary Anne Smith, Cody J. Wehrkamp, Ashley M. Mohr, Justin L. Mott

Department of Biochemistry: Faculty Publications

MicroRNAs are emerging as a hot topic in research, and rightfully so. They show great promise as targets of treatment and as markers for common human diseases, such as cancer and metabolic diseases. In this review, we address some of the basic questions regarding micro- RNA function in human disease and the clinical significance of microRNAs. Specifically, micro- RNAs in epigenetics, cancer, and metabolic diseases are discussed, with examples taken from cholangiocarcinoma and nonalcoholic fatty liver disease.

Sbml Qualitative Models: A Model Representation Format And Infrastructure To Foster Interactions Between Qualitative Modelling Formalisms And Tools, Claudine Chaouiya, Duncan Bérenguier, Sarah M. Keating, Aurélien Naldi, Martijn P. Van Iersel, Nicolas Rodriguez, Andreas Dräger, Finja Büchel, Thomas Cokelaer, Bryan Kowal, Benjamin Wicks, Emanuel Gonçalves, Julien Dorier, Michel Page, Pedro T. Monteiro, Axel Von Kamp, Ioannis Xenarios, Hidde De Jong, Michael Hucka, Steffen Klamt, Denis Thieffry, Nicolas Le Novère, Julio Saez-Rodriguez, Tomáš Helikar

Department of Biochemistry: Faculty Publications

Background: Qualitative frameworks, especially those based on the logical discrete formalism, are increasingly used to model regulatory and signalling networks. A major advantage of these frameworks is that they do not require precise quantitative data, and that they are well-suited for studies of large networks. While numerous groups have developed specific computational tools that provide original methods to analyse qualitative models, a standard format to exchange qualitative models has been missing.

Results: We present the Systems Biology Markup Language (SBML) Qualitative Models Package (“qual”), an extension of the SBML Level 3 standard designed for computer representation of qualitative …

Selenodb 2.0: Annotation Of Selenoprotein Genes In Animals And Their Genetic Diversity In Humans, Frederic Romagne, Didac Santesmasses, Louise White, Gaurab K. Sarangi, Marco Mariotti, Ron Hübler, Antje Weihmann, Genis Parra, Vadim N. Gladyshev, Roderic Guigo, Sergi Castellano

Department of Biochemistry: Faculty Publications

SelenoDB (http://www.selenodb.org) aims to provide high-quality annotations of selenoprotein genes, proteins and SECIS elements. Selenoproteins are proteins that contain the amino acid selenocysteine (Sec) and the first release of the database included annotations for eight species. Since the release of SelenoDB 1.0 many new animal genomes have been sequenced. The annotations of selenoproteins in new genomes usually contain many errors in major databases. For this reason, we have now fully annotated selenoprotein genes in 58 animal genomes. We provide manually curated annotations for human selenoproteins, whereas we use an automatic annotation pipeline to annotate selenoprotein genes in other animal genomes. …

Elucidating Causes Of Diporeia Decline In The Great Lakes Via Metabolomics: Physiological Responses After Exposure To Different Stressors, Suman Maity, Amber Jannasch, Jiri Adamec, James M. Watkins, Thomas Nalepa, Tomas O. Höök, Maria S. Sepúlveda

Department of Biochemistry: Faculty Publications

The benthic macroinvertebrate Diporeia spp. have been extirpated from many areas of the Laurentian Great Lakes, but the mechanisms underlying such declines are not fully understood. Diporeia declines coinciding with the invasion of exotic dreissenid mussels (zebra and quagga) have led to the hypothesis that Diporeia declines are a result of decreased food availability from increasing competition with dreissenids for diatoms. There is additional evidence that Diporeia are negatively affected when in close proximity to dreissenids, probably because of exposure to toxins present in the mussels’ pseudofeces. Diporeia are also known to be sensitive to anthropogenic contaminants (such as polychlorinated …

Candida Albicans Czf1 And Efg1 Coordinate The Response To Farnesol During Quorum Sensing, White-Opaque Thermal Dimorphism, And Cell Death, Melanie L. Langford, Jessica C. Hargarten, Krista D. Patefield, Elizabeth Marta, Jill R. Blankenship, Saranna Fanning, Kenneth W. Nickerson, Audrey L. Atkin

School of Biological Sciences: Faculty Publications

Quorum sensing by farnesol in Candida albicans inhibits filamentation and may be directly related to its ability to cause both mucosal and systemic diseases. The Ras1-cyclic AMP signaling pathway is a target for farnesol inhibition. However, a clear understanding of the downstream effectors of the morphological farnesol response has yet to be unraveled. To address this issue, we screened a library for mutants that fail to respond to farnesol. Six mutants were identified, and the czf1Δ/czf1Δ mutant was selected for further characterization. Czf1 is a transcription factor that regulates filamentation in embedded agar and also whiteto- opaque switching. We found …

Heritability And Inter-Population Differences In Lipid Profiles Of Drosophila Melanogaster, Cornelia J. F. Scheitz, Yu Guo, Angela M. Early, Lawrence G. Harshman, Andrew G. Clark

School of Biological Sciences: Faculty Publications

Characterizing and understanding the complex spectrum of lipids in higher organisms lags far behind our analysis of genome and transcriptome sequences. Here we generate and evaluate comprehensive lipid profiles (>200 lipids) of 92 inbred lines from five different Drosophila melanogaster populations. We find that the majority of lipid species are highly heritable, and even lipids with odd-chain fatty acids, which cannot be generated by the fly itself, also have high heritabilities. Abundance of the endosymbiont Wolbachia, a potential provider of odd-chained lipids, was positively correlated with this group of lipids. Additionally, we show that despite years of laboratory …

Cd20 Antibody Primes B Lymphocytes For Type I Interferon Production, Dongsheng Xu, Andrew Staedman, Luwen Zhang

School of Biological Sciences: Faculty Publications

CD20 is a B cell surface marker that is expressed in various stages in B lymphocytes and certain lymphomas. Clinical administration of CD20 antibody, such as rituximab, is used widely to treat human B-cell lymphomas and other diseases. However, CD20 antibody failed to treat systemic lupus erythematosus (SLE or lupus). The reason for the failure is currently unknown. Type I interferons (IFN) are a major component for the host innate immunity, and a key pathogenic factor in lupus. We found that CD20 antibody potentiated human B cells for its production of IFNs in vitro. This function was specific to …

Prevalence And Correlates Of Kaposi’S Sarcoma-Associated Herpesvirus Infection In A Sample Of Men Who Have Sex With Men In Eastern China, T. Zhang, H. Lin, V. Minhas, W. Zhu, Charles Wood, N. He

School of Biological Sciences: Faculty Publications

This study aimed to determine the seroprevalence of Kaposi’s sarcoma-associated herpesvirus (KSHV) and related factors in men who have sex with men (MSM) in China. A total of 208 subjects were recruited from eastern China from 2008 to 2009. Plasma samples were collected and screened for KSHV, HIV and syphilis. Overall, KSHV seroprevalence was 32.7% in the subjects. About 92.7% of subjects reported having ever had anal sex with a man, of whom 67.8% had receptive anal sex and 77.9% had insertive anal sex. About 93.1% of the study participants reported having had oral sex with a man, of whom …

Female Mate Choice For Multimodal Courtship And The Importance Of The Signaling Background For Selection On Male Ornamentation, Jay A. Stafstrom, Eileen A. Hebets

Eileen Hebets Publications

Conspicuous visual ornaments are frequently incorporated into complex courtship displays that integrate signal components from multiple sensory modalities. Mature male Schizocosa crassipes (Walckenaer, 1837) wolf spiders wave, arch, and tap their ornamented forelegs in a visual courtship display that simultaneously incorporates seismic components. To determine the importance of modality-specific signal components in female mate choice, we used a signal ablation design and compared the mating frequency of female-male pairs across signaling environments with manipulated modality-specific transmission properties. We found that the successful transmission of isolated visual or seismic signaling was sufficient for mating success; neither signaling modality was necessary. Additionally, …

Delayed Amyloid Plaque Deposition And Behavioral Deficits In Outcrossed Aβpp/Ps1 Mice, Brian A. Couch, Meghan E. Kerrisk, Adam C. Kaufman, Haakon B. Nygaard, Stephen M. Strittmatter, Anthony J. Koleske

School of Biological Sciences: Faculty Publications

Alzheimer’s disease (AD) is a progressive neurodegenerative dementia characterized by amyloid plaque accumulation, synapse/dendrite loss, and cognitive impairment. Transgenic mice expressing mutant forms of amyloid-β precursor protein (AβPP) and presenilin-1 (PS1) recapitulate several aspects of this disease and provide a useful model system for studying elements of AD progression. AβPP/PS1 mice have been previously shown to exhibit behavioral deficits and amyloid plaque deposition between 4–9 months of age. We crossed AβPP/PS1 animals with mice of a mixed genetic background (C57BL/6 × 129/SvJ) and investigated the development of AD-like features in the resulting outcrossed mice. The onset of memory-based behavioral impairment …

An Incompatibility Between A Mitochondrial Trna And Its Nuclear-Encoded Trna Synthetase Compromises Development And Fitness In Drosophila, Colin D. Meiklejohn, Marissa A. Holmbeck, Mohammed A. Siddiq, Dawn N. Abt, David M. Rand, Kristi L. Montooth

School of Biological Sciences: Faculty Publications

Mitochondrial transcription, translation, and respiration require interactions between genes encoded in two distinct genomes, generating the potential for mutations in nuclear and mitochondrial genomes to interact epistatically and cause incompatibilities that decrease fitness. Mitochondrial-nuclear epistasis for fitness has been documented within and between populations and species of diverse taxa, but rarely has the genetic or mechanistic basis of these mitochondrial–nuclear interactions been elucidated, limiting our understanding of which genes harbor variants causing mitochondrial–nuclear disruption and of the pathways and processes that are impacted by mitochondrial–nuclear coevolution. Here we identify an amino acid polymorphism in the Drosophila melanogaster nuclear-encoded mitochondrial tyrosyl–tRNA …

Little Evidence For Demasculinization Of The Drosophila X Chromosome Among Genes Expressed In The Male Germline, Colin D. Meiklejohn, Daven C. Presgraves

School of Biological Sciences: Faculty Publications

Male-biased genes—those expressed at higher levels in males than in females—are underrepresented on the X chromosome of Drosophila melanogaster. Several evolutionary models have been posited to explain this so-called demasculinization of the X. Here, we show that the apparent paucity of male-biased genes on the X chromosome is attributable to global X-autosome differences in expression in Drosophila testes, owing to a lack of sex chromosome dosage compensation in the male germline, but not to any difference in the density of testis-specific or testis-biased genes on the X chromosome. First,using genome-wide gene expression data from 20 tissues,we find no evidence …

Long-Term Nitrogen Amendment Alters The Diversity And Assemblage Of Soil Bacterial Communities In Tallgrass Prairie, Joseph D. Coolon, Kenneth L. Jones, Timothy C. Todd, John M. Blair, Michael A. Herman

School of Biological Sciences: Faculty Publications

Anthropogenic changes are altering the environmental conditions and the biota of ecosystems worldwide. In many temperate grasslands, such as North American tallgrass prairie, these changes include alteration in historically important disturbance regimes (e.g., frequency of fires) and enhanced availability of potentially limiting nutrients, particularly nitrogen. Such anthropogenically-driven changes in the environment are known to elicit substantial changes in plant and consumer communities aboveground, but much less is known about their effects on soil microbial communities. Due to the high diversity of soil microbes and methodological challenges associated with assessing microbial community composition, relatively few studies have addressed specific taxonomic changes …

Whole-Genome Duplication And The Functional Diversification Of Teleost Fish Hemoglobins, Juan C. Opazo, Gary Tyler Butts, Mariana F. Nery, Jay F. Storz, Federico G. Hoffmann

Jay F. Storz Publications

Subsequent to the two rounds of whole-genome duplication that occurred in the common ancestor of vertebrates, a third genome duplication occurred in the stem lineage of teleost fishes. This teleost-specific genome duplication (TGD) is thought to have provided genetic raw materials for the physiological, morphological, and behavioral diversification of this highly speciose group. The extreme physiological versatility of teleost fish is manifest in their diversity of blood–gas transport traits, which reflects the myriad solutions that have evolved to maintain tissue O₂ delivery in the face of changing metabolic demands and environmental O₂ availability during different ontogenetic stages. During …

Seroprevalence Of Brucellosis In Livestock Within Three Endemic Regions Of The Country Of Georgia, Eliso Mamisashvili, Ian T. Kracalik, Tinatin Onashvili, Lela Kerdzevadze, Ketevan Goginashvili, Tamar Tigilauri, Marina Donduashvili, Marina Nikolaishvili, Irma Beradze, Marina Zakareishvili, Maka Kokhreidze, Makvala Gelashvili, Nino Vepkhvadze, S. Elizabeth Rácz, Philip H. Elzer, Mikeljon P. Nikolich, Jason K. Blackburn

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Brucellosis is the one of most common livestock zoonoses in Georgia, resulting in significant economic losses. Livestock were sampled in three regions of Georgia (Kakheti, Kvemo Kartli, Imereti). Districts that historically reported high numbers of brucellosis related morbidity were selected for serological, bacteriological and molecular surveys. Surveying efforts yielded samples from 10,819 large and small ruminants. In total, 735 serological tests were positive on Rose Bengal and 33 bacterial isolates were recovered and identified as Brucella melitensis or Brucella abortus by microbiology and AMOS-PCR. A Bayesian framework was implemented to estimate the true prevalence of the disease given an imperfect …

Economic Analysis Of Using Renewable Wind Power System At A Signalized Intersection, Mo Zhao, Anuj Sharma, Dave G. Bernt, Joshua A. Meyer, Benjamin Dickey, Scott Rosenbaugh, Elizabeth G. Jones, Laurence Rilett

Department of Civil and Environmental Engineering: Faculty Publications

The transportation industry consumes about 28% of the total energy consumed by all sectors in the United States. This paper proposes a renewable wind power system (RWPS) as an alternative power source for signalized traffic intersections. The proposed system can be mounted onto the existing transportation infrastructure to provide reliable green electricity. Large-scale implementation of such a system has the potential to dramatically change the role of the public right-of-way system from an energy consumer to an energy producer, which will reduce the transportation system operating costs and promote the development of greener roadways.

This paper provides a framework to …

Utilities For Quantifying Separation In Pca/Pls-Da Scores Plots, Bradley Worley, Steven M. Halouska, Robert Powers

Robert Powers Publications

Metabolic fingerprinting studies rely on interpretations drawn from low-dimensional representations of spectral data generated by methods of multivariate analysis such as PCA and PLS-DA. The growth of metabolic fingerprinting and chemometric analyses involving these lowdimensional scores plots necessitates the use of quantitative statistical measures to describe significant differences between experimental groups. Our updated version of the PCAtoTree software provides methods to reliably visualize and quantify separations in scores plots through dendrograms employing both nonparametric and parametric hypothesis testing to assess node significance, as well as scores plots identifying 95% confidence ellipsoids for all experimental groups.

The Potential Of Urinary Metabolites For Diagnosing Multiple Sclerosis, Teklab Gebregiworgis, Chandirasegara Massilamany, Arunakumar Gangaplara, Sivasubramani Thulasingam, Venkata Kolli, Mark T. Werth, Eric D. Dodds, David Steffen, Jay Reddy, Robert Powers

Robert Powers Publications

A definitive diagnostic test for multiple sclerosis (MS) does not exist; instead physicians use a combination of medical history, magnetic resonance imaging, and cerebrospinal fluid analysis (CSF). Significant effort has been employed to identify biomarkers from CSF to facilitate MS diagnosis; however none of the proposed biomarkers have been successful to date. Urine is a proven source of metabolite biomarkers and has the potential to be a rapid, non-invasive, inexpensive, and efficient diagnostic tool for various human diseases. Nevertheless, urinary metabolites have not been extensively explored as a source of biomarkers for MS. Instead, we demonstrate that urinary metabolites have …

Relations Of Parenting Quality, Interparental Conflict, And Overnights With Mental Health Problems Of Children In Divorcing Families With High Legal Conflict, Irwin N. Sandler, Lorey A. Wheeler, Sanford L. Braver

Nebraska Center for Research on Children, Youth, Families, and Schools: Faculty Publications

The current study examined the associations between child mental health problems and the quality of maternal and paternal parenting, and how these associations were moderated by three contextual factors, quality of parenting by the other parent, interparental conflict, and the number of overnights parents had with the child. Data for the current study come from a sample of divorcing families who are in high legal conflict over developing or maintaining a parenting plan following divorce. Analyses revealed that the associations between child mental health problems and positive maternal and paternal parenting were moderated by the quality of parenting provided by …

Glutamine Supplementation Alleviates Vasculopathy And Corrects Metabolic Profile In An In Vivo Model Of Endothelial Cell Dysfunction., Francesco Addabbo, Qiuying Chen, Dhara P Patel, May Rabadi, Brian Ratliff, Frank Zhang, Jean-Francois Jasmin, Michael Wolin, Michael Lisanti, Steven S Gross, Michael S Goligorsky

Kimmel Cancer Center Faculty Papers

Endothelial Cell Dysfunction (ECD) is a recognized harbinger of a host of chronic cardiovascular diseases. Using a mouse model of ECD triggered by treatment with L-Nω-methylarginine (L-NMMA), we previously demonstrated that renal microvasculature displays a perturbed protein profile, including diminished expression of two key enzymes of the Krebs cycle associated with a Warburg-type suppression of mitochondrial metabolism. We hypothesized that supplementation with L-glutamine (GLN), that can enter the Krebs cycle downstream this enzymatic bottleneck, would normalize vascular function and alleviate mitochondrial dysfunction. To test this hypothesis, mice with chronic L-NMMA-induced ECD were co-treated with GLN at different concentrations for 2 …

A Phase 1b Study Of Humanized Ks-Interleukin-2 (Huks-Il2) Immunocytokine With Cyclophosphamide In Patients With Epcam-Positive Advanced Solid Tumors., Joseph P Connor, Mihaela C Cristea, Nancy L Lewis, Lionel D Lewis, Philip B Komarnitsky, Maria R Mattiacci, Mildred Felder, Sarah Stewart, Josephine Harter, Jean Henslee-Downey, Daniel Kramer, Roland Neugebauer, Roger Stupp

Kimmel Cancer Center Faculty Papers

BACKGROUND: Humanized KS-interleukin-2 (huKS-IL2), an immunocytokine with specificity for epithelial cell adhesion molecule (EpCAM), has demonstrated favorable tolerability and immunologic activity as a single agent.

METHODS: Phase 1b study in patients with EpCAM-positive advanced solid tumors to determine the maximum tolerated dose (MTD) and safety profile of huKS-IL2 in combination with low-dose cyclophosphamide. Treatment consisted of cyclophosphamide (300 mg/m2 on day 1), and escalating doses of huKS-IL2 (0.5-4.0 mg/m2 IV continuous infusion over 4 hours) on days 2, 3, and 4 of each 21-day cycle. Safety, pharmacokinetic profile, immunogenicity, anti-tumor and biologic activity were evaluated.

RESULTS: Twenty-seven patients were treated …