Digital Commons Network^™

Lafora Disease Offers A Unique Window Into Neuronal Glycogen Metabolism, Matthew S. Gentry, Joan J. Guinovart, Berge A. Minassian, Peter J. Roach, Jose M. Serratosa

Molecular and Cellular Biochemistry Faculty Publications

Lafora disease (LD) is a fatal, autosomal recessive, glycogen-storage disorder that manifests as severe epilepsy. LD results from mutations in the gene encoding either the glycogen phosphatase laforin or the E3 ubiquitin ligase malin. Individuals with LD develop cytoplasmic, aberrant glycogen inclusions in nearly all tissues that more closely resemble plant starch than human glycogen. This Minireview discusses the unique window into glycogen metabolism that LD research offers. It also highlights recent discoveries, including that glycogen contains covalently bound phosphate and that neurons synthesize glycogen and express both glycogen synthase and glycogen phosphorylase.

Fertilizing High Producing Alfalfa Stands, Edwin L. Ritchey

Kentucky Alfalfa and Stored Forage Conference

There are no secrets for successfully producing a high quality alfalfa crop. Successful alfalfa production is a product of suitable site selection, proper fertility and pH management, good pest control, and favorable weather conditions throughout the season. This paper focuses on proper fertility and pH management practices.

An Exome-Wide Sequencing Study Of Lipid Response To High-Fat Meal And Fenofibrate In Caucasians From The Goldn Cohort, Xin Geng, Marguerite R. Irvin, Bertha Hidalgo, Stella Aslibekyan, Vinodh Srinivasasainagendra, Ping An, Alexis C. Frazier-Wood, Hemant K. Tiwari, Tushar Dave, Kathleen Ryan, Jose M. Ordovas, Robert J. Straka, Mary F. Feitosa, Paul N. Hopkins, Ingrid Borecki, Michael A. Province, Braxton D. Mitchell, Donna K. Arnett, Degui Zhi

Epidemiology and Environmental Health Faculty Publications

Our understanding of genetic influences on the response of lipids to specific interventions is limited. In this study, we sought to elucidate effects of rare genetic variants on lipid response to a high-fat meal challenge and fenofibrate (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort using an exome-wide sequencing-based association study. Our results showed that the rare coding variants in ITGA7, SIPA1L2, and CEP72 are significantly associated with fasting LDL cholesterol response to FFB (P = 1.24E-07), triglyceride postprandial area under the increase (AUI) (P = 2.31E-06), and triglyceride postprandial …

Halogenated Diarylacetylenes And Methods Of Treating Cancer, Vitaliy M. Sviripa, Wen Zhang, Chunming Liu, David S. Watt

Pharmaceutical Sciences Faculty Patents

Halogenated diarylacetylenes, e.g., diarylacetylenes having at least one halo substituent in one aryl ring and an amine in the opposing aryl ring, can inhibit the proliferation of LSI 74T colon cancer cells through the inhibition of c-myc and induction of the cyclin-dependent kinase inhibitor-I (i.e., p21(Wifl/Cipl)). Such compounds are useful as antineoplastic agents.

The Premammillary Nucleus Of The Hypothalamus Is Not Necessary For Photoperiodic Timekeeping In Female Turkeys (Meleagris Gallopavo), Ashli F. Moore, Vincent M. Cassone, Kevin D. Alloway, Paul A. Bartell

Biology Faculty Publications

In birds, seasonal reproduction is regulated by day length, with long days in the spring activating the hypothalamic-pituitary-gonadal axis and reproductive behaviors. The photoreceptors mediating this process remain unknown, but recently, the premammillary nucleus (PMM) of the hypothalamus has been implicated as the site of photoperiodic signaling in turkeys. We performed electrolytic lesions of the PMM to elucidate its role in the photoactivation and maintenance of egg production in female turkeys. Our results show that ablation of the PMM does not alter the normal lay cycle. No differences were found between lesioned birds and sham controls in the latency to …

Acute Pressor Response To Psychosocial Stress Is Dependent On Endothelium‐Derived Endothelin‐1, Brandon M. Fox, Bryan K. Becker, Analia S. Loria, Kelly A. Hyndman, Chunhua Jin, Hannah Clark, Robin Johns, Masashi Yanagisawa, David M. Pollock, Jennifer S. Pollock

Pharmacology and Nutritional Sciences Faculty Publications

Background

Acute psychosocial stress provokes increases in circulating endothelin‐1 (ET‐1) levels in humans and animal models. However, key questions about the physiological function and cellular source of stress‐induced ET‐1 remain unanswered. We hypothesized that endothelium‐derived ET‐1 contributes to the acute pressor response to stress via activation of the endothelin A receptor.

Methods and Results

Adult male vascular endothelium‐specific ET‐1 knockout mice and control mice that were homozygous for the floxed allele were exposed to acute psychosocial stress in the form of cage switch stress (CSS), with blood pressure measured by telemetry. An acute pressor response was elicited by CSS in …

A Lin28b Tumor-Specific Transcript In Cancer, Weijie Guo, Zhixiang Hu, Yichao Bao, Yuchen Li, Shengli Li, Qiupeng Zheng, Dongbin Lyu, Di Chen, Tao Yu, Yan Li, Xiaodong Zhu, Jie Ding, Yingjun Zhao, Xianghuo He, Shenglin Huang

Markey Cancer Center Faculty Publications

The diversity and complexity of the cancer transcriptome may contain transcripts unique to the tumor environment. Here, we report a LIN28B variant, LIN28B-TST, which is specifically expressed in hepatocellular carcinoma (HCC) and many other cancer types. Expression of LIN28B-TST is associated with significantly poor prognosis in HCC patients. LIN28B-TST initiates from a de novo alternative transcription initiation site that harbors a strong promoter regulated by NFYA but not c-Myc. Demethylation of the LIN28B-TST promoter might be a prerequisite for its transcription and transcriptional regulation. LIN28B-TST encodes a protein isoform with additional N-terminal amino acids and is critical for cancer …

Effects Of Predispersal Insect Seed Predation On The Early Life History Stages Of A Rare Cold Sand-Desert Legume, Yi J. Han, Jerry M. Baskin, Dun Y. Tan, Carol C. Baskin, Ming Y. Wu

Biology Faculty Publications

Seed predation by insects is common in seeds of Fabaceae (legume) species with physical dormancy (PY). However, the consequences of insect seed predation on the life history of legumes with PY have been little studied. In the largest genus of seed plants, Astragalus (Fabaceae), only one study has tested the effects of insect predation on germination, and none has tested it directly on seedling survival. Thus, we tested the effects of insect predation on seed germination and seedling growth and survival of Astragalus lehmannianus, a central Asian sand-desert endemic. Under laboratory conditions, seeds lightly predated in the natural habitat …

Phaeophleospora Vochysiae Savi & Glienke Sp. Nov. Isolated From Vochysia Divergens Found In The Pantanal, Brazil, Produces Bioactive Secondary Metabolites, Daiani C. Savi, Khaled A. Shaaban, Francielly M. W. Gos, Larissa V. Ponomareva, Jon S. Thorson, Chirlei Glienke, Jürgen Rohr

Pharmaceutical Sciences Faculty Publications

Microorganisms associated with plants are highly diverse and can produce a large number of secondary metabolites, with antimicrobial, anti-parasitic and cytotoxic activities. We are particularly interested in exploring endophytes from medicinal plants found in the Pantanal, a unique and widely unexplored wetland in Brazil. In a bio-prospecting study, strains LGMF1213 and LGMF1215 were isolated as endophytes from Vochysia divergens, and by morphological and molecular phylogenetic analyses were characterized as Phaeophleospora vochysiae sp. nov. The chemical assessment of this species reveals three major compounds with high biological activity, cercoscosporin (1), isocercosporin (2) and the new compound 3-(sec-butyl)-6-ethyl-4,5-dihydroxy-2-methoxy-6-methylcyclohex-2-enone (3). …

Modified Single Prolonged Stress Reduces Cocaine Self-Administration During Acquisition Regardless Of Rearing Environment, Rebecca S. Hofford, Mark A. Prendergast, Michael T. Bardo

Psychology Faculty Publications

Until recently, there were few rodent models available to study the interaction of post-traumatic stress disorder (PTSD) and drug taking. Like PTSD, single prolonged stress (SPS) produces hypothalamic-pituitary-adrenal (HPA) axis dysfunction and alters psychostimulant self-administration. Other stressors, such as isolation stress, also alter psychostimulant self-administration. However, it is currently unknown if isolation housing combined with SPS can alter the acquisition or maintenance of cocaine self-administration. The current study applied modified SPS (modSPS; two hours restraint immediately followed by cold swim stress) to rats raised in an isolation condition (Iso), enrichment condition (Enr), or standard condition (Std) to measure changes in …

Nmda Receptor Blockade Specifically Impedes The Acquisition Of Incentive Salience Attribution, Jonathan J. Chow, Joshua S. Beckmann

Psychology Faculty Publications

Glutamatergic signaling plays an important role in learning and memory. Using Pavlovian conditioned approach procedures, the mechanisms that drive stimulus-reward learning and memory have been investigated. However, there are instances where reward-predictive stimuli can function beyond being solely predictive and can be attributed with “motivational value” or incentive salience. Using a Pavlovian conditioned approach procedure consisting of two different but equally predictive stimuli (lever vs. tone) we investigated the role NMDA receptor function has in the attribution of incentive salience. The results revealed that the administration of MK-801, an NMDA receptor antagonist, during acquisition of Pavlovian conditioned approach promoted goal-tracking …

Downregulation Of Srebp Inhibits Tumor Growth And Initiation By Altering Cellular Metabolism In Colon Cancer, Yang-An Wen, Xiaopeng Xiong, Yekaterina Y. Zaytseva, Dana L. Napier, Emma Vallee, Austin T. Li, Chi Wang, Heidi L. Weiss, B. Mark Evers, Tianyan Gao

Markey Cancer Center Faculty Publications

Sterol regulatory element-binding proteins (SREBPs) belong to a family of transcription factors that regulate the expression of genes required for the synthesis of fatty acids and cholesterol. Three SREBP isoforms, SREBP1a, SREBP1c, and SREBP2, have been identified in mammalian cells. SREBP1a and SREBP1c are derived from a single gene through the use of alternative transcription start sites. Here we investigated the role of SREBP-mediated lipogenesis in regulating tumor growth and initiation in colon cancer. Knockdown of either SREBP1 or SREBP2 decreased levels of fatty acids as a result of decreased expression of SREBP target genes required for lipid biosynthesis in …

Individual And Combined Effects Of Herbicide Tribenuron-Methyl And Fungicide Tebuconazole On Soil Earthworm Eisenia Fetida, Jiqiang Chen, Muhammad Saleem, Caixia Wang, Wenxing Liang, Qingming Zhang

Plant and Soil Sciences Faculty Publications

Earthworms are soil engineers that alter the soil bio-physical properties to favor plant growth whereas pesticides represent a significant threat to their abundance and soil health. Thus, we investigated the toxic effects of tribenuron-methyl (TBM) and tebuconazole (TEB) on the soil earthworm, Eisenia fetida. The TBM demonstrated low toxicity to E. fetida in the contact filter paper and artificial soil tests, with median lethal concentrations (LC₅₀) of 135.6 μg cm⁻² at 48 h and 511 mg kg⁻¹ on day 14, respectively. Similarly, TEB also showed low toxicity to E. fetida in the artificial …

Advancing Behavioural Genomics By Considering Timescale, Clare C. Rittschof, Kimberly A. Hughes

Entomology Faculty Publications

Animal behavioural traits often covary with gene expression, pointing towards a genomic constraint on organismal responses to environmental cues. This pattern highlights a gap in our understanding of the time course of environmentally responsive gene expression, and moreover, how these dynamics are regulated. Advances in behavioural genomics explore how gene expression dynamics are correlated with behavioural traits that range from stable to highly labile. We consider the idea that certain genomic regulatory mechanisms may predict the timescale of an environmental effect on behaviour. This temporally minded approach could inform both organismal and evolutionary questions ranging from the remediation of early …

Distinct Properties Underlie Flavin-Based Electron Bifurcation In A Novel Electron Transfer Flavoprotein Fixab From Rhodopseudomonas Palustris, H. Diessel Duan, Carolyn E. Lubner, Monika Tokmina-Lukaszewska, George H. Gauss, Brian Bothner, Paul W. King, John W. Peters, Anne-Frances Miller

Chemistry Faculty Publications

A newly recognized third fundamental mechanism of energy conservation in biology, electron bifurcation, uses free energy from exergonic redox reactions to drive endergonic redox reactions. Flavin-based electron bifurcation furnishes low-potential electrons to demanding chemical reactions, such as reduction of dinitrogen to ammonia. We employed the heterodimeric flavoenzyme FixAB from the diazotrophic bacterium Rhodopseudomonas palustris to elucidate unique properties that underpin flavin-based electron bifurcation. FixAB is distinguished from canonical electron transfer flavoproteins (ETFs) by a second FAD that replaces the AMP of canonical ETF. We exploited near-UV–visible CD spectroscopy to resolve signals from the different flavin sites in FixAB and to …

Reference Gene Selection For Rt-Qpcr Analysis In Harmonia Axyridis, A Global Invasive Lady Beetle, Xiaowei Yang, Huipeng Pan, Ling Yuan, Xuguo Zhou

Entomology Faculty Publications

Harmonia axyridis is a voracious predator, a biological control agent, and one of the world most invasive insect species. The advent of next-generation sequencing platforms has propelled entomological research into the genomics and post-genomics era. Real-time quantitative PCR (RT-qPCR), a primary tool for gene expression analysis, is a core technique governs the genomic research. The selection of internal reference genes, however, can significantly impact the interpretation of RT-qPCR results. The overall goal of this study is to identify the reference genes in the highly invasive H. axyridis. Our central hypothesis is that the suitable reference genes for RT-qPCR analysis …

Insulin-Degrading Enzyme Is Not Secreted From Cultured Cells, Eun Suk Song, David W. Rodgers, Louis Hersh

Molecular and Cellular Biochemistry Faculty Publications

Insulin-degrading enzyme (IDE) functions in the catabolism of bioactive peptides. Established roles include degrading insulin and the amyloid beta peptide (Aβ), linking it to diabetes and Alzheimer’s disease. IDE is primarily located in the cytosol, and a longstanding question is how it gains access to its peptide substrates. Reports suggest that IDE secreted by an unconventional pathway participates in extracellular hydrolysis of insulin and Aβ. We find that IDE release from cultured HEK-293 or BV-2 cells represents only ~1% of total cellular IDE, far less than has been reported previously. Importantly, lactate dehydrogenase (LDH) and other cytosolic enzymes are released …

Influence Of Damming On Anuran Species Richness In Riparian Areas: A Test Of The Serial Discontinuity Concept, Jacquelyn C. Guzy, Evan A. Eskew, Brian J. Halstead, Steve J. Price

Forestry and Natural Resources Faculty Publications

Almost all large rivers worldwide are fragmented by dams, and their impacts have been modeled using the serial discontinuity concept (SDC), a series of predictions regarding responses of key biotic and abiotic variables. We evaluated the effects of damming on anuran communities along a 245‐km river corridor by conducting repeated, time‐constrained anuran calling surveys at 42 locations along the Broad and Pacolet Rivers in South Carolina, USA. Using a hierarchical Bayesian analysis, we test the biodiversity prediction of the SDC (modified for floodplain rivers) by evaluating anuran occupancy and species diversity relative to dams and degree of urbanized land use. …

Auditing Snomed Ct Hierarchical Relations Based On Lexical Features Of Concepts In Non-Lattice Subgraphs, Licong Cui, Olivier Bodenreider, Jay Shi, Guo-Qiang Zhang

Computer Science Faculty Publications

Objective—We introduce a structural-lexical approach for auditing SNOMED CT using a combination of non-lattice subgraphs of the underlying hierarchical relations and enriched lexical attributes of fully specified concept names. Our goal is to develop a scalable and effective approach that automatically identifies missing hierarchical IS-A relations.

Methods—Our approach involves 3 stages. In stage 1, all non-lattice subgraphs of SNOMED CT’s IS-A hierarchical relations are extracted. In stage 2, lexical attributes of fully-specified concept names in such non-lattice subgraphs are extracted. For each concept in a non-lattice subgraph, we enrich its set of attributes with attributes from its ancestor …

Genome-Wide Interactions With Dairy Intake For Body Mass Index In Adults Of European Descent, Caren E. Smith, Jack L. Follis, Hassan S. Dashti, Toshiko Tanaka, Mariaelisa Graff, Amanda M. Fretts, Tuomas O. Kilpeläinen, Mary K. Wojczynski, Kris Richardson, Mike A. Nalls, Christina-Alexandra Schulz, Yongmei Liu, Alexis C. Frazier-Wood, Esther Van Eekelen, Carol Wang, Paul S. De Vries, Vera Mikkilä, Rebecca Rohde, Bruce M. Psaty, Torben Hansen, Mary F. Feitosa, Chao-Qiang Lai, Denise K. Houston, Luigi Ferruci, Ulrika Ericson, Zhe Wang, Renée De Mutsert, Wendy H. Oddy, Ester A. L. De Jonge, Ilkka Seppälä, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Scope: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter‐individual variability in associations between body weight and dairy consumption.

Methods and results: A genome‐wide interaction study to discover genetic variants that account for variation in BMI in the context of low‐fat, high‐fat and total dairy intake in cross‐sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta‐analyzed. Twenty‐six genetic variants reached the selected significance threshold (p‐interaction <10⁻⁷⁾, and six independent variants (LINC01512‐rs7751666, PALM2/AKAP2‐rs914359, ACTA2‐rs1388, PPP1R12A‐rs7961195, LINC00333‐rs9635058, …

Reproductive Steroids And Adhd Symptoms Across The Menstrual Cycle, Bethan A. Roberts, Tory Eisenlohr-Moul, Michelle M. Martel

Psychology Faculty Publications

Although Attention-Deficit/Hyperactivity Disorder shows (ADHD) male predominance, females are significantly impaired and exhibit additional comorbid disorders during adolescence. However, no empirical work has examined the influence of cyclical fluctuating steroids on ADHD symptoms in women. The present study examined estradiol (E2), progesterone (P4), and testosterone (T) associations with ADHD symptoms across the menstrual cycle in regularly-cycling young women (N=32), examining trait impulsivity as a moderator. Women completed a baseline measure of trait impulsivity, provided saliva samples each morning, and completed an ADHD symptom checklist every evening for 35 days. Results indicated decreased levels of E2 in the context of increased …

Treated Hypothyroidism Is Associated With Cerebrovascular Disease But Not Alzheimer's Disease Pathology In Older Adults, Willa D. Brenowitz, Fang Han, Walter A. Kukull, Peter T. Nelson

Pathology and Laboratory Medicine Faculty Publications

Thyroid hormone (TH) disease is common among older adults and is associated with cognitive impairment. However, pathologic correlates are not well understood. We studied pathologic and clinical factors associated with hypothyroidism, the most common form of TH disease, in research subjects seen annually for clinical evaluations at U.S. Alzheimer’s Disease Centers. Thyroid disease and treatment status were assessed during clinician interviews. Among autopsied subjects, there were 555 participants with treated hypothyroidism and 2,146 with no known thyroid disease; hypothyroidism was associated with severe atherosclerosis (OR=1.35 95% CI: 1.02, 1.79) but not Alzheimer’s disease (AD) pathologies (amyloid plaques or neurofibrillary tangles). …

Novel Fluconazole Derivatives With Promising Antifungal Activity, Nishad Thamban Chandrika, Sanjib K. Shrestha, Huy X. Ngo, Kaitlind C. Howard, Sylvie Garneau-Tsodikova

Pharmaceutical Sciences Faculty Publications

The fungistatic nature and toxicity concern associated with the azole drugs currently on the market have resulted in an increased demand for new azole antifungal agents for which these problematic characteristics do not exist. The extensive use of azoles has resulted in fungal strains capable of resisting the action of these drugs. Herein, we report the synthesis and antifungal activities of novel fluconazole (FLC) analogues with alkyl-, aryl-, cycloalkyl-, and dialkyl-amino substituents. We evaluated their antifungal activity by MIC determination and time-kill assay as well as their safety profile by hemolytic activity against murine erythrocytes as well as cytotoxicity against …

Contractile Response Of Bovine Lateral Saphenous Vein To Ergotamine Tartrate Exposed To Different Concentrations Of Molecularly Imprinted Polymer, Manoj B. Kudupoje, James L. Klotz, Alexandros Yiannikouris, Karl A. Dawson, Kyle R. Mcleod, Eric S. Vanzant

Animal and Food Sciences Faculty Publications

Ergot alkaloids, in their active isomeric form, affect animal health and performance, and adsorbents are used to mitigate toxicities by reducing bioavailability. Adsorbents with high specificity (molecularly imprinted polymers: MIP) adsorb ergot alkaloids in vitro, but require evaluation for biological implications. Using ex vivo myography, synthetic polymers were evaluated for effects on the bioactivity of ergotamine tartrate (ETA). Polymers were first evaluated using isotherms. Lateral saphenous veins were collected from 17 steers for four independent studies: dose response of ETA, adsorbent dose response, validation of pre-myograph incubation conditions and MIP/ non-molecularly imprinted polymer (NIP) comparison. Norepinephrine normalized percent contractile response …

Development Of Body Emotion Perception In Infancy: From Discrimination To Recognition, Alison Heck, Alyson Chroust, Hannah B. White, Rachel Lynn Jubran, Ramesh S. Bhatt

Psychology Faculty Publications

Research suggests that infants progress from discrimination to recognition of emotions in faces during the first half year of life. It is unknown whether the perception of emotions from bodies develops in a similar manner. In the current study, when presented with happy and angry body videos and voices, 5-month-olds looked longer at the matching video when they were presented upright but not when they were inverted. In contrast, 3.5-month-olds failed to match even with upright videos. Thus, 5-month-olds but not 3.5-month-olds exhibited evidence of recognition of emotions from bodies by demonstrating intermodal matching. In a subsequent experiment, younger infants …

Minocycline Protects Developing Brain Against Ethanol-Induced Damage, Xin Wang, Kai Zhang, Fanmuyi Yang, Zhenhua Ren, Mei Xu, Jacqueline A. Frank, Zun-Ji Ke, Jia Luo

Pharmacology and Nutritional Sciences Faculty Publications

Fetal alcohol spectrum disorders (FASD) are caused by ethanol exposure during the pregnancy and is the leading cause of mental retardation. Ethanol exposure during the development results in the loss of neurons in the developing brain, which may underlie many neurobehavioral deficits associated with FASD. It is important to understand the mechanisms underlying ethanol-induced neuronal loss and develop appropriate therapeutic strategies. One of the potential mechanisms involves neuroimmune activation. Using a third trimester equivalent mouse model of ethanol exposure, we demonstrated that ethanol induced a wide-spread neuroapoptosis, microglial activation, and neuroinflammation in C57BL/6 mice. Minocycline is an antibiotic that inhibits …

Does Pre-Assessment Work?, Thomas R. Guskey

Educational, School, and Counseling Psychology Faculty Publications

Educators must understand the purpose, form, and content of pre-assessments to reap their potential benefits.

Coleopteran Communities Associated With Forests Invaded By Emerald Ash Borer, Matthew B. Savage, Lynne K. Rieske

Entomology Faculty Publications

Extensive ash mortality caused by the non-native emerald ash borer alters canopy structure and creates inputs of coarse woody debris as dead and dying ash fall to the forest floor; this affects habitat heterogeneity; resource availability; and exposure to predation and parasitism. As EAB-induced (emerald ash borer-induced) disturbance progresses the native arthropod associates of these forests may be irreversibly altered through loss of habitat; changing abiotic conditions and altered trophic interactions. We documented coleopteran communities associated with EAB-disturbed forests in a one-year study to evaluate the nature of these changes. Arthropods were collected via ethanol-baited traps on five sites with …

Adropin: An Endocrine Link Between The Biological Clock And Cholesterol Homeostasis, Sarbani Ghoshal, Joseph R. Stevens, Cyrielle Billon, Clemence Girardet, Sadichha Sitaula, Arthur S. Leon, D.C. Rao, James S. Skinner, Tuomo Rankinen, Claude Bouchard, Marinelle V. Nuñez, Kimber L. Stanhope, Deborah A. Howatt, Alan Daugherty, Jinsong Zhang, Matthew Schuelke, Edward P. Weiss, Alisha R. Coffey, Brian J. Bennett, Praveen Sethupathy, Thomas P. Burris, Peter J. Havel, Andrew A. Butler

Physiology Faculty Publications

Objective

Identify determinants of plasma adropin concentrations, a secreted peptide translated from the Energy Homeostasis Associated (ENHO) gene linked to metabolic control and vascular function.

Methods

Associations between plasma adropin concentrations, demographics (sex, age, BMI) and circulating biomarkers of lipid and glucose metabolism were assessed in plasma obtained after an overnight fast in humans. The regulation of adropin expression was then assessed in silico, in cultured human cells, and in animal models.

Results

In humans, plasma adropin concentrations are inversely related to atherogenic LDL-cholesterol (LDL-C) levels in men (n = 349), but not in women (n = …

Amine Containing Analogs Of Sulindac For Cancer Prevention, Bini Mathew, Judith V. Hobrath, Michele C. Connelly, R. Kiplin Guy, Robert C. Reynolds

Pharmaceutical Sciences Faculty Publications

Background:

Sulindac belongs to the chemically diverse family of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) that effectively prevent adenomatous colorectal polyps and colon cancer, especially in patients with familial adenomatous polyposis. Sulindac sulfide amide (SSA), an amide analog of sulindac sulfide, shows insignificant COX-related activity and toxicity while enhancing anticancer activity in vitro and demonstrating in vivo xenograft activity.

Objective:

Develop structure-activity relationships in the sulindac amine series and identify analogs with promising anticancer activities.

Method:

A series of sulindac amine analogs were designed and synthesized and then further modified in a “libraries from libraries” approach to produce amide, sulfonamide and N,N-disubstituted …