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https://www.readbyqxmd.com/read/28722829/megakaryocytes-enhance-mesenchymal-stromal-cells-proliferation-and-inhibit-differentiation
#1
Arbi M Emmakah, Hussain E Arman, Marta B Alvarez, Paul J Childress, Joseph P Bidwell, William S Goebel, Tien-Min Gabriel Chu, Melissa A Kacena
Megakaryocytes (MKs) can induce proliferation of calvarial osteoblasts [Ciovacco et al., 2009], but this same phenomenon has not been reported for bone marrow stromal populations from long bones. Bone marrow contains several types of progenitor cells which can be induced to differentiate into multiple cell types. Herein, we examined mesenchymal stromal cell proliferation and osteoblastic differentiation when rabbit or mouse MK were cultured with i) rabbit bone marrow stromal cells, ii) rabbit dental pulp stromal cells, or iii) mouse bone marrow stromal cells...
July 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28637206/improving-combination-osteoporosis-therapy-in-a-preclinical-model-of-heightened-osteoanabolism
#2
Yu Shao, Selene Hernandez-Buquer, Paul Childress, Keith R Stayrook, Marta B Alvarez, Hannah Davis, Lilian Plotkin, Yongzheng He, Keith W Condon, David B Burr, Stuart J Warden, Alexander G Robling, Feng-Chun Yang, Ronald C Wek, Matthew R Allen, Joseph P Bidwell
Combining anti-catabolic agents with parathyroid hormone (PTH) to enhance bone mass has yielded mixed results in osteoporosis patients. Towards the goal of enhancing the efficacy of these regimens, we tested their utility in combination with loss of the transcription factor Nmp4 since disabling this gene amplifies PTH-induced increases in trabecular bone in mice by boosting osteoblast secretory activity. We addressed whether combining a sustained anabolic response with an anti-catabolic results in superior bone acquisition compared to PTH mono-therapy...
June 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/28512748/genetic-influences-on-adhd-symptom-dimensions-examination-of-a-priori-candidates-gene-based-tests-genome-wide-variation-and-snp-heritability
#3
L Cinnamon Bidwell, Joshua C Gray, Jessica Weafer, Abraham A Palmer, Harriet de Wit, James MacKillop
Although the heritability of ADHD is estimated to be high, identifying specific genetic markers remains challenging. Most studies to date have examined the genetic basis of ADHD by employing dichotomous diagnostic phenotypes, but, as ADHD symptoms tend to be phenotypically dimensional, an alternative and potentially informative approach is to examine continuous indices of inattention and hyperactivity-impulsivity symptoms. The current study aimed to identify genetic effects on dimensionally-focused adult ADHD-related phenotypes in 990 individuals of European ancestry with intentionally low levels of substance misuse to avoid confounding...
June 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28166328/comparative-effectiveness-of-vancomycin-and-metronidazole-for-the-prevention-of-recurrence-and-death-in-patients-with-clostridium-difficile-infection
#4
COMPARATIVE STUDY
Vanessa W Stevens, Richard E Nelson, Elyse M Schwab-Daugherty, Karim Khader, Makoto M Jones, Kevin A Brown, Tom Greene, Lindsay D Croft, Melinda Neuhauser, Peter Glassman, Matthew Bidwell Goetz, Matthew H Samore, Michael A Rubin
Importance: Metronidazole hydrochloride has historically been considered first-line therapy for patients with mild to moderate Clostridium difficile infection (CDI) but is inferior to vancomycin hydrochloride for clinical cure. The choice of therapy may likewise have substantial consequences on other downstream outcomes, such as recurrence and mortality, although these secondary outcomes have been less studied. Objective: To evaluate the risk of recurrence and all-cause 30-day mortality among patients receiving metronidazole or vancomycin for the treatment of mild to moderate and severe CDI...
April 1, 2017: JAMA Internal Medicine
https://www.readbyqxmd.com/read/28060286/the-use-of-ex-vivo-whole-organ-imaging-and-quantitative-tissue-histology-to-determine-the-bio-distribution-of-fluorescently-labeled-molecules
#5
Jeremy W D McGowan, Gene L Bidwell
Fluorescent labeling is a well-established process for examining the fate of labeled molecules under a variety of experimental conditions both in vitro and in vivo. Fluorescent probes are particularly useful in determining the bio-distribution of administered large molecules, where the addition of a small-molecule fluorescent label is unlikely to affect the kinetics or bio-distribution of the compound. A variety of methods exist to examine bio-distribution that vary significantly in the amount of effort required and whether the resulting measurements are fully quantitative, but using multiple methods in conjunction can provide a rapid and effective system for analyzing bio-distributions...
December 24, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27892853/structure-of-the-germline-genome-of-tetrahymena-thermophila-and-relationship-to-the-massively-rearranged-somatic-genome
#6
Eileen P Hamilton, Aurélie Kapusta, Piroska E Huvos, Shelby L Bidwell, Nikhat Zafar, Haibao Tang, Michalis Hadjithomas, Vivek Krishnakumar, Jonathan H Badger, Elisabet V Caler, Carsten Russ, Qiandong Zeng, Lin Fan, Joshua Z Levin, Terrance Shea, Sarah K Young, Ryan Hegarty, Riza Daza, Sharvari Gujja, Jennifer R Wortman, Bruce W Birren, Chad Nusbaum, Jainy Thomas, Clayton M Carey, Ellen J Pritham, Cédric Feschotte, Tomoko Noto, Kazufumi Mochizuki, Romeo Papazyan, Sean D Taverna, Paul H Dear, Donna M Cassidy-Hanley, Jie Xiong, Wei Miao, Eduardo Orias, Robert S Coyne
The germline genome of the binucleated ciliate Tetrahymena thermophila undergoes programmed chromosome breakage and massive DNA elimination to generate the somatic genome. Here, we present a complete sequence assembly of the germline genome and analyze multiple features of its structure and its relationship to the somatic genome, shedding light on the mechanisms of genome rearrangement as well as the evolutionary history of this remarkable germline/soma differentiation. Our results strengthen the notion that a complex, dynamic, and ongoing interplay between mobile DNA elements and the host genome have shaped Tetrahymena chromosome structure, locally and globally...
November 28, 2016: ELife
https://www.readbyqxmd.com/read/27784692/a-kidney-selective-biopolymer-for-targeted-drug-delivery
#7
Gene L Bidwell, Fakhri Mahdi, Qingmei Shao, Omar C Logue, Jamarius P Waller, Caleb Reese, Alejandro R Chade
Improving drug delivery to the kidney using renal-targeted therapeutics is a promising but underdeveloped area. We aimed to develop a kidney-targeting construct for renal-specific drug delivery. Elastin-like polypeptides (ELPs) are nonimmunogenic protein-based carriers that can stabilize attached small-molecule and peptide therapeutics. We modified ELP at its NH2-terminus with a cyclic, seven-amino acid kidney-targeting peptide (KTP) and at its COOH-terminus with a cysteine residue for tracer conjugation. Comparative in vivo pharmacokinetics and biodistribution in rat and swine models and in vitro cell binding studies using human renal cells were performed...
January 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27660412/intranasal-administration-of-elastin-like-polypeptide-for-therapeutic-delivery-to-the-central-nervous-system
#8
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
https://www.readbyqxmd.com/read/27573812/notch-activation-drives-adipocyte-dedifferentiation-and-tumorigenic-transformation-in-mice
#9
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
https://www.readbyqxmd.com/read/27389588/preeclampsia-and-the-brain-neural-control-of-cardiovascular-changes-during-pregnancy-and-neurological-outcomes-of-preeclampsia
#10
REVIEW
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-)
https://www.readbyqxmd.com/read/27367910/therapeutic-angiogenesis-by-vascular-endothelial-growth-factor-supplementation-for-treatment-of-renal-disease
#11
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
https://www.readbyqxmd.com/read/26972897/placental-origins-of-adverse-pregnancy-outcomes-potential-molecular-targets-an-executive-workshop-summary-of-the-eunice-kennedy-shriver-national-institute-of-child-health-and-human-development
#12
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
https://www.readbyqxmd.com/read/26856261/genomic-insights-into-the-ixodes-scapularis-tick-vector-of-lyme-disease
#13
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...
February 9, 2016: Nature Communications
https://www.readbyqxmd.com/read/26672799/corneal-penetrating-elastin-like-polypeptide-carriers
#14
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
https://www.readbyqxmd.com/read/26541349/renal-therapeutic-angiogenesis-using-a-bioengineered-polymer-stabilized-vascular-endothelial-growth-factor-construct
#15
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
https://www.readbyqxmd.com/read/26455482/human-g109e-inhibitor-1-impairs-cardiac-function-and-promotes-arrhythmias
#16
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
https://www.readbyqxmd.com/read/26410615/an-initial-investigation-of-associations-between-dopamine-linked-genetic-variation-and-smoking-motives-in-african-americans
#17
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
https://www.readbyqxmd.com/read/26244796/genome-wide-mapping-and-interrogation-of-the-nmp4-antianabolic-bone-axis
#18
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
https://www.readbyqxmd.com/read/26228775/challenges-and-new-strategies-for-therapeutic-peptide-delivery-to-the-cns
#19
REVIEW
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
https://www.readbyqxmd.com/read/26165999/nitroreductase-triggered-activation-of-a-novel-caged-fluorescent-probe-obtained-from-methylene-blue
#20
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
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