Digital Commons Network^™

Seed Germination Responses To Seasonal Temperature And Drought Stress Are Species‐Specific But Not Related To Seed Size In A Desert Steppe: Implications For Effect Of Climate Change On Community Structure, Fengyan Yi, Zhaoren Wang, Carol C. Baskin, Jerry M. Baskin, Ruhan Ye, Hailian Sun, Yuanyuan Zhang, Xuehua Ye, Guofang Liu, Xuejun Yang, Zhenying Huang

Biology Faculty Publications

Investigating how seed germination of multiple species in an ecosystem responds to environmental conditions is crucial for understanding the mechanisms for community structure and biodiversity maintenance. However, knowledge of seed germination response of species to environmental conditions is still scarce at the community level. We hypothesized that responses of seed germination to environmental conditions differ among species at the community level, and that germination response is not correlated with seed size. To test this hypothesis, we determined the response of seed germination of 20 common species in the Siziwang Desert Steppe, China, to seasonal temperature regimes (representing April, May, June, …

Multi-Tissue Transcriptomes Of Caecilian Amphibians Highlight Incomplete Knowledge Of Vertebrate Gene Families, María Torres-Sánchez, Christopher J. Creevey, Etienne Kornobis, David J. Gower, Mark Wilkinson, Diego San Mauro

Neuroscience Faculty Publications

RNA sequencing (RNA-seq) has become one of the most powerful tools to unravel the genomic basis of biological adaptation and diversity. Although challenging, RNA-seq is particularly promising for research on non-model, secretive species that cannot be observed in nature easily and therefore remain comparatively understudied. Among such animals, the caecilians (order Gymnophiona) likely constitute the least known group of vertebrates, despite being an old and remarkably distinct lineage of amphibians. Here, we characterize multi-tissue transcriptomes for five species of caecilians that represent a broad level of diversity across the order. We identified vertebrate homologous elements of caecilian functional genes of …

A Phewas Study Of A Large Observational Epidemiological Cohort Of African Americans From The Regards Study, Xueyan Zhao, Xin Geng, Vinodh Srinivasasainagendra, Ninad Chaudhary, Suzanne Judd, Virginia Wadley, Orlando M. Gutiérrez, Henry Wang, Ethan M. Lange, Leslie A. Lange, Daniel Woo, Frederick W. Unverzagt, Monika Safford, Mary Cushman, Nita Limdi, Rakale Quarells, Donna K. Arnett, Marguerite R. Irvin, Degui Zhi

Epidemiology and Environmental Health Faculty Publications

Background: Cardiovascular disease, diabetes, and kidney disease are among the leading causes of death and disability worldwide. However, knowledge of genetic determinants of those diseases in African Americans remains limited.

Results: In our study, associations between 4956 GWAS catalog reported SNPs and 67 traits were examined among 7726 African Americans from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study, which is focused on identifying factors that increase stroke risk. The prevalent and incident phenotypes studied included inflammation, kidney traits, cardiovascular traits and cognition. Our results validated 29 known associations, of which eight associations were reported for the …

Optimizing Gastrointestinal Integrity In Poultry: The Role Of Nutrients And Feed Additives, Sunday A. Adedokun, Opeyemi C. Olojede

Animal and Food Sciences Faculty Publications

Immunomodulation of the immune system by stimulating or suppressing one or both arms, is an emerging concept driven by the understanding of the host defense system. In particular, the gastrointestinal tract (GIT) functions not only as a site for digestion and absorption of nutrients but also acts as a metabolic and immunological organ. This serves as a barrier against abnormal presentation of luminal constituents, caused by dysfunctional intestinal epithelial barrier, to the mucosal immune system. Invasion by pathogens in the case of disease or stress or a massive influx of commensal bacteria overcomes the defensive mechanisms, resulting in the full …

Sleeping Through Anything: The Effects Of Unpredictable Disruptions On Mouse Sleep, Healing, And Affect, Amy Robinson-Junker, Bruce O'Hara, Abigail Durkes, Brianna Gaskill

Biology Faculty Publications

Many aspects of the laboratory environment are not tailored to the needs of rodents, which may cause stress. Unpredictable stressors can cause ulcers, prolonged pituitary-adrenal activation, and anhedonia. Similarly, pain has been demonstrated to slow wound healing, and mice experiencing pain exhibit altered behavior. However it is unknown how husbandry, which occurs when the mice are inactive, and lack of analgesia, specifically in a punch biopsy procedure, effects animal physiology, behavior, and welfare, particularly as it relates to sleep fragmentation. We hypothesized that sleep fragmentation, induced by unpredictable husbandry and lack of pain management will slow wound healing. Two main …

Cytisine-Linked Isoflavonoid Antineoplastic Agents For The Treatment Of Cancer, Chunming Liu, David S. Watt, Mykhaylo S. Frasinyuk, Vitaliy M. Sviripa, Wen Zhang, Svitlana P. Bondarenko

Markey Cancer Center Faculty Patents

Cytisine-linked isoflavonoids, or pharmaceutically acceptable salts thereof or pharmaceutically acceptable compositions thereof, are useful for the treatment of conditions in which cells have a reliance on peroxisomal HSD17B4 to degrade very long chain fatty acids and provide necessary energy for cell proliferation, such as is seen in colorectal cancer and prostate cancer, for example.

Overview Of The Biocreative Vi Precision Medicine Track: Mining Protein Interactions And Mutations For Precision Medicine, Rezarta Islamaj Doğan, Sun Kim, Andrew Chatr-Aryamontri, Chih-Hsuan Wei, Donald C. Comeau, Rui Antunes, Sérgio Matos, Qingyu Chen, Aparna Elangovan, Nagesh C. Panyam, Karin Verspoor, Hongfang Liu, Yanshan Wang, Zhuang Liu, Berna Altınel, Zehra Melce Hüsünbeyi, Arzucan Özgür, Aris Fergadis, Chen-Kai Wang, Hong-Jie Dai, Tung Tran, Ramakanth Kavuluru, Ling Luo, Albert Steppi, Jinfeng Zhang, Jinchan Qu, Zhiyong Lu

Computer Science Faculty Publications

The Precision Medicine Initiative is a multicenter effort aiming at formulating personalized treatments leveraging on individual patient data (clinical, genome sequence and functional genomic data) together with the information in large knowledge bases (KBs) that integrate genome annotation, disease association studies, electronic health records and other data types. The biomedical literature provides a rich foundation for populating these KBs, reporting genetic and molecular interactions that provide the scaffold for the cellular regulatory systems and detailing the influence of genetic variants in these interactions. The goal of BioCreative VI Precision Medicine Track was to extract this particular type of information and …

Immunization Of Alpacas (Lama Pacos) With Protein Antigens And Production Of Antigen-Specific Single Domain Antibodies, K. Martin Chow, Sidney W. Whiteheart, Jeffrey R. Smiley, Savita Sharma, Kathy Boaz, Meggie J. Coleman, Alvina Maynard, Louis B. Hersh, Craig W. Vander Kooi

Molecular and Cellular Biochemistry Faculty Publications

In this manuscript, a method for the immunization of alpaca and the use of molecular biology methods to produce antigen-specific single domain antibodies is described and demonstrated. Camelids, such as alpacas and llamas, have become a valuable resource for biomedical research since they produce a novel type of heavy chain-only antibody which can be used to produce single domain antibodies. Because the immune system is highly flexible, single domain antibodies can be made to many different protein antigens, and even different conformations of the antigen, with a very high degree of specificity. These features, among others, make single domain antibodies …

Wildfire Alters Spatial Patterns Of Available Soil Nitrogen And Understory Environments In A Valley Boreal Larch Forest, Jianjian Kong, Jian Yang, Bo Liu, Lin Qi

Forestry and Natural Resources Faculty Publications

Wildfire, a primary natural disturbance in many forests, affects soil nutrient availability and spatial distributions of forest plants. However, post-fire changes in soil nutrients and spatial patterns of understory environments at fine scales are poorly understood. Here, we characterized spatial patterns of soil nitrogen availability and site characteristics at a 3-year-post-fire and an unburned site in a valley boreal larch forest. We also examined the relationship between soil nitrogen availability and site characteristics. The results showed that the burned site had higher NO₃⁻ and lower NH₄⁺ than the control. The herb, litter and coarse wood debris …

Itch Nuclear Translocation And H1.2 Polyubiquitination Negatively Regulate The Dna Damage Response, Lufen Chang, Lei Shen, Hu Zhou, Jing Gao, Hangyi Pan, Li Zheng, Brian Armstrong, Yang Peng, Guang Peng, Binhua P. Zhou, Steven T. Rosen, Binghui Shen

Molecular and Cellular Biochemistry Faculty Publications

The downregulation of the DNA damage response (DDR) enables aggressive tumors to achieve uncontrolled proliferation against replication stress, but the mechanisms underlying this process in tumors are relatively complex. Here, we demonstrate a mechanism through which a distinct E3 ubiquitin ligase, ITCH, modulates DDR machinery in triple-negative breast cancer (TNBC). We found that expression of a nuclear form of ITCH was significantly increased in human TNBC cell lines and tumor specimens. Phosphorylation of ITCH at Ser257 by AKT led to the nuclear localization of ITCH and ubiquitination of H1.2. The ITCH-mediated polyubiquitination of H1.2 suppressed RNF8/RNF168-dependent formation of 53BP1 foci, …

Biosynthetic And Synthetic Strategies For Assembling Capuramycin-Type Antituberculosis Antibiotics, Ashley L. Biecker, Xiaodong Liu, Jon S. Thorson, Zhaoyong Yang, Steven G. Van Lanen

Pharmaceutical Sciences Faculty Publications

Mycobacterium tuberculosis (Mtb) has recently surpassed HIV/AIDS as the leading cause of death by a single infectious agent. The standard therapeutic regimen against tuberculosis (TB) remains a long, expensive process involving a multidrug regimen, and the prominence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and totally drug-resistant (TDR) strains continues to impede treatment success. An underexplored class of natural products—the capuramycin-type nucleoside antibiotics—have been shown to have potent anti-TB activity by inhibiting bacterial translocase I, a ubiquitous and essential enzyme that functions in peptidoglycan biosynthesis. The present review discusses current literature concerning the biosynthesis and chemical synthesis of capuramycin …

Absence Of Endothelial Α5Β1 Integrin Triggers Early Onset Of Experimental Autoimmune Encephalomyelitis Due To Reduced Vascular Remodeling And Compromised Vascular Integrity, Ravi Kant, Sebok K. Halder, Gregory J. Bix, Richard Milner

Sanders-Brown Center on Aging Faculty Publications

Early in the development of multiple sclerosis (MS) and its mouse model experimental autoimmune encephalomyelitis (EAE), vascular integrity is compromised. This is accompanied by a marked vascular remodeling response, though it is currently unclear whether this is an adaptive vascular repair mechanism or is part of the pathogenic process. In light of the well-described angiogenic role for the α5β1 integrin, the goal of this study was to evaluate how genetic deletion of endothelial α5 integrin (α5-EC-KO mice) impacts vascular remodeling and repair following vascular disruption during EAE pathogenesis, and how this subsequently influences clinical progression and inflammatory demyelination. Immunofluorescence staining …

Circular Rna Circnol10 Inhibits Lung Cancer Development By Promoting Sclm1-Mediated Transcriptional Regulation Of The Humanin Polypeptide Family, Aruo Nan, Lijian Chen, Nan Zhang, Yangyang Jia, Xin Li, Hanyu Zhou, Yihui Ling, Zhishan Wang, Chengfeng Yang, Sijin Liu, Yiguo Jiang

Toxicology and Cancer Biology Faculty Publications

circNOL10 is a circular RNA expressed at low levels in lung cancer, though its functions in lung cancer remain unknown. Here, the function and molecular mechanism of circNOL10 in lung cancer development are investigated using in vitro and in vivo studies, and it is shown that circNOL10 significantly inhibits the development of lung cancer and that circNOL10 expression is co‐regulated by methylation of its parental gene Pre‐NOL10 and by splicing factor epithelial splicing regulatory protein 1 (ESRP1). circNOL10 promotes the expression of transcription factor sex comb on midleg‐like 1 (SCML1) by inhibiting transcription factor ubiquitination and thus also affects regulation …

Cerebrovascular Smooth Muscle Cells As The Drivers Of Intramural Periarterial Drainage Of The Brain, Roxana Aldea, Roy O. Weller, Donna M. Wilcock, Roxana O Carare, Giles Richardson

Physiology Faculty Publications

The human brain is the organ with the highest metabolic activity but it lacks a traditional lymphatic system responsible for clearing waste products. We have demonstrated that the basement membranes of cerebral capillaries and arteries represent the lymphatic pathways of the brain along which intramural periarterial drainage (IPAD) of soluble metabolites occurs. Failure of IPAD could explain the vascular deposition of the amyloid-beta protein as cerebral amyloid angiopathy (CAA), which is a key pathological feature of Alzheimer's disease. The underlying mechanisms of IPAD, including its motive force, have not been clarified, delaying successful therapies for CAA. Although arterial pulsations from …

Cytochrome P450s And Uses Thereof, Joseph Chappell, Lyle F. Ralston

Pharmaceutical Sciences Faculty Patents

The invention relates to isolated cytochrome P450 polypeptides and nucleic acid molecules, as well as expression vectors and transgenic plants containing these molecules. In addition, the invention relates to uses of such molecules in methods of increasing the level of resistance against a disease caused by a plant pathogen in a transgenic plant, in methods for producing altered compounds, for example, hydroxylated compounds, and in methods of producing isoprenoid compounds.

Multi-Ancestry Study Of Blood Lipid Levels Identifies Four Loci Interacting With Physical Activity, Tuomas O. Kilpeläinen, Amy R. Bentley, Raymond Noordam, Yun Ju Sung, Karen Schwander, Thomas W. Winkler, Hermina Jakupović, Daniel I. Chasman, Alisa Manning, Ioanna Ntalla, Hugues Aschard, Michael R. Brown, Lisa De Las Fuentes, Nora Franceschini, Xiuqing Guo, Dina Vojinovic, Stella Aslibekyan, Mary F. Feitosa, Minjung Kho, Solomon K. Musani, Melissa Richard, Heming Wang, Zhe Wang, Traci M. Bartz, Lawrence F. Bielak, Archie Campbell, Rajkumar Dorajoo, Virginia Fisher, Fernando P. Hartwig, Andrea R. V. R. Horimoto, Donna K. Arnett

Epidemiology and Environmental Health Faculty Publications

Many genetic loci affect circulating lipid levels, but it remains unknown whether lifestyle factors, such as physical activity, modify these genetic effects. To identify lipid loci interacting with physical activity, we performed genome-wide analyses of circulating HDL cholesterol, LDL cholesterol, and triglyceride levels in up to 120,979 individuals of European, African, Asian, Hispanic, and Brazilian ancestry, with follow-up of suggestive associations in an additional 131,012 individuals. We find four loci, in/near CLASP1, LHX1, SNTA1, and CNTNAP2, that are associated with circulating lipid levels through interaction with physical activity; higher levels of physical activity enhance the HDL …

Cytochrome P450s And Uses Thereof, Joseph Chappell, Lyle F. Ralston

Pharmaceutical Sciences Faculty Patents

The invention relates to isolated cytochrome P450 polypeptides and nucleic acid molecules, as well as expression vectors and transgenic plants containing these molecules. In addition, the invention relates to uses of such molecules in methods of increasing the level of resistance against a disease caused by a plant pathogen in a transgenic plant, in methods for producing altered compounds, for example, hydroxylated compounds, and in methods of producing isoprenoid compounds.

Profitability At Eldon Farms: Guiding Principles, John Genho

Forage Symposium at the Kentucky Cattlemen’s Convention

Eldon Farms is a 7,000-acre farm in the Northern Piedmont of Virginia. Over the past 15 years, we have adopted a grazing program based on three principles. While the specifics of each operation are different, I believe these principles can be applied across a host of situations.

Forages At Kca Foreword [2019], Christopher D. Teutsch, Christi L. Forsythe, Rehanon Pampell

Forage Symposium at the Kentucky Cattlemen’s Convention

No abstract provided.

Coatings On Mammalian Cells: Interfacing Cells With Their Environment, Kara A. Davis, Pei-Jung Wu, Calvin F. Cahall, Cong Li, Anuhya Gottipati, Brad J. Berron

Chemical and Materials Engineering Faculty Publications

The research community is intent on harnessing increasingly complex biological building blocks. At present, cells represent a highly functional component for integration into higher order systems. In this review, we discuss the current application space for cellular coating technologies and emphasize the relationship between the target application and coating design. We also discuss how the cell and the coating interact in common analytical techniques, and where caution must be exercised in the interpretation of results. Finally, we look ahead at emerging application areas that are ideal for innovation in cellular coatings. In all, cellular coatings leverage the machinery unique to …

Antisense Oligonucleotides Targeting Angiotensinogen: Insights From Animal Studies, Chia-Hua Wu, Ya Wang, Murong Ma, Adam E. Mullick, Rosanne M. Crooke, Mark J. Graham, Alan Daugherty, Hong S. Lu

Saha Cardiovascular Research Center Faculty Publications

Angiotensinogen (AGT) is the unique substrate of all angiotensin peptides. We review the recent preclinical research of AGT antisense oligonucleotides (ASOs), a rapidly evolving therapeutic approach. The scope of the research findings not only opens doors for potentially new therapeutics of hypertension and many other diseases, but also provides insights into understanding critical physiological and pathophysiological roles mediated by AGT.

Good To The Last Drop: The Emergence Of Coffee Ringspot Virus, Michael Goodin, Antonia Dos Reis Figueira

Plant Pathology Faculty Publications

Two and a half billion times per day a human hand reaches for a fresh cup of coffee. Although arguably dispensable for life per se, with an industry value of US$174 billion, coffee provides the lifeblood that sustains economies of producing countries located in the “coffee belt” situated between the Tropics of Cancer and Capricorn. As a “solvent” in which many human interactions take place, coffee is witness to the broad spectrum of human activities from the mundane to the pleasurable and personal. However, in opposition to its economic, cultural, and physiological importance, diseases such as coffee rust (caused by …

Allogeneic Hematopoietic Cell Transplantation Provides Effective Salvage Despite Refractory Disease Or Failed Prior Autologous Transplant In Angioimmunoblastic T-Cell Lymphoma: A Cibmtr Analysis, Narendranath Epperla, Kwang W. Ahn, Carlos Litovich, Sairah Ahmed, Minoo Battiwalla, Jonathon B. Cohen, Parastoo Dahi, Nosha Farhadfar, Umar Farooq, Cesar O. Freytes, Nilanjan Ghosh, Bradley Haverkos, Alex Herrera, Mark Hertzberg, Gerhard C. Hildebrandt, David Inwards, Mohamed A. Kharfan-Dabaja, Farhad Khimani, Hillard Lazarus, Aleksandr Lazaryan, Lazaros Lekakis, Hemant Murthy, Sunita Nathan, Taiga Nishihori, Attaphol Pawarode, Tim Prestidge, Praveen Ramakrishnan, Andrew R. Rezvani, Rizwan Romee, Nirav N. Shah

Internal Medicine Faculty Publications

Background: There is a paucity of data on the role of allogeneic hematopoietic cell transplantation (allo-HCT) in patients with angioimmunoblastic T-cell lymphoma (AITL). Using the CIBMTR registry, we report here the outcomes of AITL patients undergoing an allo-HCT.

Methods: We evaluated 249 adult AITL patients who received their first allo-HCT during 2000–2016.

Results: The median patient age was 56 years (range = 21–77). Majority of the patients were Caucasians (86%), with a male predominance (60%). Graft-versus-host disease (GVHD) prophylaxis was predominantly calcineurin inhibitor-based approaches while the most common graft source was peripheral blood (97%). Median follow-up of survivors was 49 …

Bishydrazone-Based Antifungal Agents, Sylvie Garneau-Tsodikova, David S. Watt

Pharmaceutical Sciences Faculty Patents

Hydrazone compounds and pharmaceutical compositions including same are disclosed as having antifungal activity. Such compounds are useful for treating or preventing fungal conditions in a subject in need thereof by administering same.

Plasmodium Para-Aminobenzoate Synthesis And Salvage Resolve Avoidance Of Folate Competition And Adaptation To Host Diet, Joachim Michael Matz, Mutsumi Watanabe, Mofolusho Falade, Takayuki Tohge, Rainer Hoefgen, Kai Matuschewski

Pharmaceutical Sciences Faculty Publications

Folate metabolism is essential for DNA synthesis and a validated drug target in fast-growing cell populations, including tumors and malaria parasites. Genome data suggest that Plasmodium has retained its capacity to generate folates de novo. However, the metabolic plasticity of folate uptake and biosynthesis by the malaria parasite remains unresolved. Here, we demonstrate that Plasmodium uses an aminodeoxychorismate synthase and an aminodeoxychorismate lyase to promote the biogenesis of the central folate precursor para-aminobenzoate (pABA) in the cytoplasm. We show that the parasite depends on de novo folate synthesis only when dietary intake of pABA by …

Star-Related Lipid Transfer Protein 10 (Stard10): A Novel Key Player In Alcohol-Induced Breast Cancer Progression, Andrea Floris, Jia Luo, Jacqueline A. Frank, Jennifer Zhou, Sandro Orrù, Michela Biancolella, Sabina Pucci, Augusto Orlandi, Paolo Campagna, Antonella Balzano, Komal Ramani, Maria Lauda Tomasi

Pharmacology and Nutritional Sciences Faculty Publications

Background: Ethanol abuse promotes breast cancer development, metastasis and recurrence stimulating mammary tumorigenesis by mechanisms that remain unclear. Normally, 35% of breast cancer is Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2)-positive that predisposes to poor prognosis and relapse, while ethanol drinking leads to invasion of their ERBB2 positive cells triggering the phosphorylation status of mitogen-activated protein kinase. StAR-related lipid transfer protein 10 (STARD10) is a lipid transporter of phosphatidylcholine (PC) and phosphatidylethanolamine (PE); changes on membrane composition of PC and PE occur before the morphological tumorigenic events. Interestingly, STARD10 has been described to be highly expressed in 35–40% of ERBB2-positive breast …

Maternal Work Hours And Childhood Obesity: Evidence Using Instrumental Variables Related To Sibling School Eligibility, Charles J. Courtemanche, Rusty Tchernis, Xilin Zhou

Economics Faculty Publications

This study exploits plausibly exogenous variation derived from the youngest sibling’s school eligibility to estimate the effects of maternal work on the weight outcomes of older children. We first show that mothers’ work hours increase gradually along both the extensive and intensive margins as the age of the youngest child rises, whereas mothers’ spouses’ work hours do not appear to be responsive. We develop an instrumental-variables model that shows that mothers’ work hours lead to larger increases in children’s body mass index z-scores and probabilities of being overweight/obese than those identified in previous studies. Subsample analyses find that the …

Toward An Understanding Of Behavioral And Sensory Experiences When Living With Dementia And Related Disorders: An Environmental Gerontology Perspective, Elizabeth K. Rhodus

Theses and Dissertations--Gerontology

Behavioral and psychological symptoms of dementia create challenges for those living with neurodegenerative cognitive impairment and their care partners. Pharmacological approaches for treatment of challenging behaviors seen in dementia have limited success and serious side effects. Because of this, nonpharmacological approaches are being investigated with increasing frequency. Of particular interest are nonpharmacological approaches involving environmental stimulation to change behaviors. Success of such approaches relies on sensory processing systems, personal preferences, and environmental congruence. There is limited evidence describing behaviors of persons with cognitive impairment in relation to these components. Currently, there is no guiding model for implementation of environmental and …

A Not-So Beautiful Mind: A Review Of The Genetics Of Schizophrenia, Lydia Pack

Oswald Research and Creativity Competition

Schizophrenia is often called “the cancer of the brain” because of the lifelong, horrendous implications of the disease. Though research has been conducted on schizophrenia for a century or more, it has just recently been realized how large a role genetics may play in the development of the disease. This review will discuss why research on schizophrenia genes has been difficult, what genes have been found, how the current treatments are being revolutionized, and how to progress in this field. The difficulty in research is due in part to the complex genetics behind the disease as well as possible environmental …

2018 Kentucky River Watershed Watch: Annual Report, Malissa Mcalister

Kentucky River Watershed Watch

No abstract provided.