Read by QxMD icon Read

Gene bidwell

Jeremy Wd McGowan, Qingmei Shao, Parminder Js Vig, Gene L Bidwell
Bypassing the blood-brain barrier is one of the primary considerations when designing compounds intended to function in the central nervous system (CNS). Intranasal (IN) administration of otherwise blood-brain barrier impermeable molecules can result in high CNS concentrations and low systemic accumulation, indicating that IN administration may be a useful method of delivering therapeutics to the CNS. Elastin-like polypeptide (ELP) is a large, non-immunogenic, highly manipulable biopolymer with extensive evidence supporting its use as a carrier with the ability to improve drug pharmacokinetics and drug targeting...
2016: Drug Design, Development and Therapy
Pengpeng Bi, Feng Yue, Anju Karki, Beatriz Castro, Sara E Wirbisky, Chao Wang, Abigail Durkes, Bennett D Elzey, Ourania M Andrisani, Christopher A Bidwell, Jennifer L Freeman, Stephen F Konieczny, Shihuan Kuang
Liposarcomas (LPSs) are the most common soft-tissue cancer. Because of the lack of animal models, the cellular origin and molecular regulation of LPS remain unclear. Here, we report that mice with adipocyte-specific activation of Notch signaling (Ad/N1ICD) develop LPS with complete penetrance. Lineage tracing confirms the adipocyte origin of Ad/N1ICD LPS. The Ad/N1ICD LPS resembles human dedifferentiated LPS in histological appearance, anatomical localization, and gene expression signature. Before transformation, Ad/N1ICD adipocytes undergo dedifferentiation that leads to lipodystrophy and metabolic dysfunction...
September 19, 2016: Journal of Experimental Medicine
Omar C Logue, Eric M George, Gene L Bidwell
Preeclampsia (PE) is a form of gestational hypertension that complicates ∼5% of pregnancies worldwide. Over 70% of the fatal cases of PE are attributed to cerebral oedema, intracranial haemorrhage and eclampsia. The aetiology of PE originates from abnormal remodelling of the maternal spiral arteries, creating an ischaemic placenta that releases factors that drive the pathophysiology. An initial neurological outcome of PE is the absence of the autonomically regulated cardiovascular adaptations to pregnancy...
August 1, 2016: Clinical Science (1979-)
Omar C Logue, Jeremy W D McGowan, Eric M George, Gene L Bidwell
PURPOSE OF REVIEW: Vascular endothelial growth factors (VEGFs) influence renal function through angiogenesis, with VEGF-A being the most potent inducer of vascular formation. In the normal glomerulus, tight homeostatic balance is maintained between the levels of VEGF-A isoforms produced by podocyte cells, and the VEGF receptors (VEGFRs) expressed by glomerular endothelial, mesangial, and podocyte cells. Renal disease occurs when this homeostatic balance is lost, manifesting in the abnormal autocrine and paracrine VEGF-A/VEGFR signaling, ultrastructural glomerular and tubular damage, and impaired filtration...
September 2016: Current Opinion in Nephrology and Hypertension
John V Ilekis, Ekaterini Tsilou, Susan Fisher, Vikki M Abrahams, Michael J Soares, James C Cross, Stacy Zamudio, Nicholas P Illsley, Leslie Myatt, Christine Colvis, Maged M Costantine, David M Haas, Yoel Sadovsky, Carl Weiner, Erik Rytting, Gene Bidwell
Although much progress is being made in understanding the molecular pathways in the placenta that are involved in the pathophysiology of pregnancy-related disorders, a significant gap exists in the utilization of this information for the development of new drug therapies to improve pregnancy outcome. On March 5-6, 2015, the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health sponsored a 2-day workshop titled Placental Origins of Adverse Pregnancy Outcomes: Potential Molecular Targets to begin to address this gap...
July 2016: American Journal of Obstetrics and Gynecology
Monika Gulia-Nuss, Andrew B Nuss, Jason M Meyer, Daniel E Sonenshine, R Michael Roe, Robert M Waterhouse, David B Sattelle, José de la Fuente, Jose M Ribeiro, Karine Megy, Jyothi Thimmapuram, Jason R Miller, Brian P Walenz, Sergey Koren, Jessica B Hostetler, Mathangi Thiagarajan, Vinita S Joardar, Linda I Hannick, Shelby Bidwell, Martin P Hammond, Sarah Young, Qiandong Zeng, Jenica L Abrudan, Francisca C Almeida, Nieves Ayllón, Ketaki Bhide, Brooke W Bissinger, Elena Bonzon-Kulichenko, Steven D Buckingham, Daniel R Caffrey, Melissa J Caimano, Vincent Croset, Timothy Driscoll, Don Gilbert, Joseph J Gillespie, Gloria I Giraldo-Calderón, Jeffrey M Grabowski, David Jiang, Sayed M S Khalil, Donghun Kim, Katherine M Kocan, Juraj Koči, Richard J Kuhn, Timothy J Kurtti, Kristin Lees, Emma G Lang, Ryan C Kennedy, Hyeogsun Kwon, Rushika Perera, Yumin Qi, Justin D Radolf, Joyce M Sakamoto, Alejandro Sánchez-Gracia, Maiara S Severo, Neal Silverman, Ladislav Šimo, Marta Tojo, Cristian Tornador, Janice P Van Zee, Jesús Vázquez, Filipe G Vieira, Margarita Villar, Adam R Wespiser, Yunlong Yang, Jiwei Zhu, Peter Arensburger, Patricia V Pietrantonio, Stephen C Barker, Renfu Shao, Evgeny M Zdobnov, Frank Hauser, Cornelis J P Grimmelikhuijzen, Yoonseong Park, Julio Rozas, Richard Benton, Joao H F Pedra, David R Nelson, Maria F Unger, Jose M C Tubio, Zhijian Tu, Hugh M Robertson, Martin Shumway, Granger Sutton, Jennifer R Wortman, Daniel Lawson, Stephen K Wikel, Vishvanath M Nene, Claire M Fraser, Frank H Collins, Bruce Birren, Karen E Nelson, Elisabet Caler, Catherine A Hill
Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing ∼57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions...
2016: Nature Communications
Eric M George, Fakhri Mahdi, Omar C Logue, Grant G Robinson, Gene L Bidwell
PURPOSE: Elastin-like polypeptide (ELP) is a bioengineered protein widely applied as a drug carrier due to its biocompatibility and amenability to modification with cell-penetrating peptides (CPPs) and therapeutic agents. The purpose of this study was to determine whether topically applied ELP or CPP-fused ELPs penetrate the corneal barrier. METHODS: In vitro binding and cytotoxicity to human corneal epithelial (HCE) cells were determined for ELP or CPP-ELPs. Corneal binding, clearance, and penetration were assessed in a rabbit model following topical application of the fluorescently labeled proteins by quantitative fluorescence imaging and histology...
April 2016: Journal of Ocular Pharmacology and Therapeutics
Alejandro R Chade, Nathan A Tullos, Taylor W Harvey, Fakhri Mahdi, Gene L Bidwell
Renovascular disease (RVD) induces renal microvascular (MV) rarefaction that drives progressive kidney injury. In previous studies, we showed that renal vascular endothelial growth factor (VEGF) therapy attenuated MV damage, but did not resolve renal injury at practical clinical doses. To increase the bioavailability of VEGF, we developed a biopolymer-stabilized elastin-like polypeptide (ELP)-VEGF fusion protein and determined its in vivo potential for therapeutic renal angiogenesis in RVD using an established swine model of chronic RVD...
June 2016: Journal of the American Society of Nephrology: JASN
Kobra Haghighi, Tracy J Pritchard, Guan-Sheng Liu, Vivek P Singh, Philip Bidwell, Chi Keung Lam, Elizabeth Vafiadaki, Parthib Das, Jianyong Ma, Swati Kunduri, Despina Sanoudou, Stela Florea, Erica Vanderbilt, Hong-Shang Wang, Jack Rubinstein, Roger J Hajjar, Evangelia G Kranias
A hallmark of human and experimental heart failure is deficient sarcoplasmic reticulum (SR) Ca-uptake reflecting impaired contractile function. This is at least partially attributed to dephosphorylation of phospholamban by increased protein phosphatase 1 (PP1) activity. Indeed inhibition of PP1 by transgenic overexpression or gene-transfer of constitutively active inhibitor-1 improved Ca-cycling, preserved function and decreased fibrosis in small and large animal models of heart failure, suggesting that inhibitor-1 may represent a potential therapeutic target...
December 2015: Journal of Molecular and Cellular Cardiology
L C Bidwell, J E McGeary, J C Gray, R H C Palmer, V S Knopik, J MacKillop
Nicotine dependence (ND) is a heterogeneous phenotype with complex genetic influences that may vary across ethnicities. The use of intermediate phenotypes may clarify genetic influences and reveal specific etiological pathways. Prior work in European Americans has found that the four Primary Dependence Motives (PDM) subscales (Automaticity, Craving, Loss of Control, and Tolerance) of the Wisconsin Inventory of Smoking Motives represent core features of nicotine dependence and are promising intermediate phenotypes for understanding genetic pathways to ND...
November 2015: Pharmacology, Biochemistry, and Behavior
Paul Childress, Keith R Stayrook, Marta B Alvarez, Zhiping Wang, Yu Shao, Selene Hernandez-Buquer, Justin K Mack, Zachary R Grese, Yongzheng He, Daniel Horan, Fredrick M Pavalko, Stuart J Warden, Alexander G Robling, Feng-Chun Yang, Matthew R Allen, Venkatesh Krishnan, Yunlong Liu, Joseph P Bidwell
PTH is an osteoanabolic for treating osteoporosis but its potency wanes. Disabling the transcription factor nuclear matrix protein 4 (Nmp4) in healthy, ovary-intact mice enhances bone response to PTH and bone morphogenetic protein 2 and protects from unloading-induced osteopenia. These Nmp4(-/-) mice exhibit expanded bone marrow populations of osteoprogenitors and supporting CD8(+) T cells. To determine whether the Nmp4(-/-) phenotype persists in an osteoporosis model we compared PTH response in ovariectomized (ovx) wild-type (WT) and Nmp4(-/-) mice...
September 2015: Molecular Endocrinology
Jeremy Wd McGowan, Gene L Bidwell, Parminder Js Vig
Therapeutic peptides represent a largely untapped resource in medicine today, especially in the central nervous system. Despite their ease of design and remarkably high target specificity, it is difficult to deliver them beyond the blood-brain barrier or into the required intracellular compartments. In addition, the instability of these peptides in vivo precludes their use to combat the symptoms of numerous neurological disorders including Alzheimer's disease and spinocerebellar ataxia. In this review, we aim to characterize recent advances in the delivery of therapeutic peptides to the central nervous system past the blood-brain barrier and discuss the advantages and disadvantages of the examined methods as well as explore new potential directions...
July 2015: Therapeutic Delivery
Jungeun Bae, Louis E McNamara, Manal A Nael, Fakhri Mahdi, Robert J Doerksen, Gene L Bidwell, Nathan I Hammer, Seongbong Jo
A near-infrared fluorescent probe based on methylene blue (p-NBMB) was developed for the detection of nitroreductase. Conjugating methylene blue with a p-nitrobenzyl moiety enables it to be activated by nitroreductase-catalyzed 1,6-elimination, resulting in the release of an active methylene blue fluorophore.
August 18, 2015: Chemical Communications: Chem Comm
Eric M George, Huiling Liu, Grant G Robinson, Fakhri Mahdi, Eddie Perkins, Gene L Bidwell
BACKGROUND: Therapeutic angiogenesis with vascular endothelial growth factor (VEGF), delivered either via recombinant protein infusion or via gene therapy, has shown promise in preclinical models of various diseases including myocardial infarction, renovascular disease, preeclampsia, and neurodegenerative disorders. However, dosing, duration of expression, and tissue specificity are challenges to VEGF gene therapy, and recombinant VEGF delivery suffers from extremely rapid plasma clearance, necessitating continuous infusion and/or direct injection at the site of interest...
2015: Vascular Cell
Kobra Haghighi, Philip Bidwell, Evangelia G Kranias
Depressed sarcoplasmic reticulum (SR) calcium cycling, reflecting impaired SR Ca-transport and Ca-release, is a key and universal characteristic of human and experimental heart failure. These SR processes are regulated by multimeric protein complexes, including protein kinases and phosphatases as well as their anchoring and regulatory subunits that fine-tune Ca-handling in specific SR sub-compartments. SR Ca-transport is mediated by the SR Ca-ATPase (SERCA2a) and its regulatory phosphoprotein, phospholamban (PLN)...
December 2014: Journal of Molecular and Cellular Cardiology
Vivek Krishnakumar, Maria Kim, Benjamin D Rosen, Svetlana Karamycheva, Shelby L Bidwell, Haibao Tang, Christopher D Town
Medicago truncatula, a close relative of alfalfa (Medicago sativa), is a model legume used for studying symbiotic nitrogen fixation, mycorrhizal interactions and legume genomics. J. Craig Venter Institute (JCVI; formerly TIGR) has been involved in M. truncatula genome sequencing and annotation since 2002 and has maintained a web-based resource providing data to the community for this entire period. The website ( has seen major updates in the past year, where it currently hosts the latest version of the genome (Mt4...
January 2015: Plant & Cell Physiology
Rohan H C Palmer, Leslie Brick, Nicole R Nugent, L Cinnamon Bidwell, John E McGeary, Valerie S Knopik, Matthew C Keller
BACKGROUND AND AIMS: Twin and family studies suggest that genetic influences are shared across substances of abuse. However, despite evidence of heritability, genome-wide association and candidate gene studies have indicated numerous markers of limited effects, suggesting that much of the heritability remains missing. We estimated (1) the aggregate effect of common single nucleotide polymorphisms (SNPs) on multiple indicators of comorbid drug problems that are typically employed across community and population-based samples, and (2) the genetic covariance across these measures...
March 2015: Addiction
Gene L Bidwell, Eric M George
The last several decades have seen intensive research into the molecular mechanisms underlying the symptoms of preeclampsia. While the underlying cause of preeclampsia is believed to be defective placental development and resulting placental ischemia, it is only recently that the links between the ischemic placenta and maternal symptomatic manifestation have been elucidated. Several different pathways have been implicated in the development of the disorder; most notably production of the anti-angiogenic protein sFlt-1, induction of auto-immunity and inflammation, and production of reactive oxygen species...
2014: Frontiers in Pharmacology
Eric M George, Huiling Liu, Grant G Robinson, Gene L Bidwell
BACKGROUND: Pregnant females are largely overlooked in drug development due to concerns for fetal health. Additionally, pregnancy is often an exclusion criterion in clinical trials, so the safety of many drugs during pregnancy is unknown. PURPOSE: The goal of this study was to evaluate Elastin-like Polypeptide (ELP), a synthetic protein derived from human elastin, for maternally sequestered drug delivery. ELP is a versatile drug carrier with a long plasma half-life, low immunogenicity, and the ability to be fused to nearly any small molecule or protein-based therapeutic...
December 2014: Journal of Drug Targeting
C A Bidwell, J N Waddell, T M Taxis, H Yu, R L Tellam, M K Neary, N E Cockett
The callipyge phenotype in sheep involves substantial postnatal muscle hypertrophy and other changes to carcass composition. A single nucleotide polymorphism in the DLK1-DIO3 imprinted gene cluster alters gene expression of the paternal allele-specific protein-coding genes and several maternal allele-specific long noncoding RNA and microRNA when the mutation is inherited in cis. The inheritance pattern of the callipyge phenotype is polar overdominant because muscle hypertrophy only occurs in heterozygous animals that inherit a normal maternal allele and the callipyge SNP on the paternal allele (+/C)...
August 2014: Animal Genetics
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"