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Vasiliki Tsakraklides, Annapurna Kamineni, Andrew L Consiglio, Kyle MacEwen, Jonathan Friedlander, Hannah G Blitzblau, Maureen A Hamilton, Donald V Crabtree, Austin Su, Jonathan Afshar, John E Sullivan, W Greg LaTouf, Colin R South, Emily H Greenhagen, A Joe Shaw, Elena E Brevnova
Background: Oleate-enriched triacylglycerides are well-suited for lubricant applications that require high oxidative stability. Fatty acid carbon chain length and degree of desaturation are key determinants of triacylglyceride properties and the ability to manipulate fatty acid composition in living organisms is critical to developing a source of bio-based oil tailored to meet specific application requirements. Results: We sought to engineer the oleaginous yeast Yarrowia lipolytica for production of high-oleate triacylglyceride oil...
2018: Biotechnology for Biofuels
Valeria I Fink, Cathy A Jenkins, Jessica L Castilho, Anna K Person, Bryan E Shepherd, Beatriz Grinsztejn, Juliana Netto, Brenda Crabtree-Ramirez, Claudia P Cortés, Denis Padgett, Karu Jayathilake, Catherine McGowan, Pedro Cahn
Background: This study aimed to evaluate trends and predictors of survival after cancer diagnosis in persons living with HIV in the Caribbean, Central, and South America network for HIV epidemiology cohort. Methods: Demographic, cancer, and HIV-related data from HIV-positive adults diagnosed with cancer ≤ 1 year before or any time after HIV diagnosis from January 1, 2000-June 30, 2015 were retrospectively collected. Cancer cases were classified as AIDS-defining cancers (ADC) and non-AIDS-defining cancers (NADC)...
2018: Infectious Agents and Cancer
Jennifer R Hemler, Jennifer D Hall, Raja A Cholan, Benjamin F Crabtree, Laura J Damschroder, Leif I Solberg, Sarah S Ono, Deborah J Cohen
PURPOSE: Practice facilitators ("facilitators") can play an important role in supporting primary care practices in performing quality improvement (QI), but they need complete and accurate clinical performance data from practices' electronic health records (EHR) to help them set improvement priorities, guide clinical change, and monitor progress. Here, we describe the strategies facilitators use to help practices perform QI when complete or accurate performance data are not available...
May 2018: Journal of the American Board of Family Medicine: JABFM
Michael D Crabtree, Carolina A T F Mendonça, Quenton R Bubb, Jane Clarke
Intrinsically disordered regions are present in one third of eukaryotic proteins and are overrepresented in cellular processes such as signaling, suggesting that intrinsically disordered proteins (IDPs) may have a functional advantage over folded proteins. Upon interacting with a partner macromolecule, a subset of IDPs can fold and bind to form a well-defined three-dimensional conformation. For example, disordered BH3-only proteins bind promiscuously to a large number of homologous BCL-2-family proteins, where they fold to a helical structure in a groove on the BCL-2-like protein surface...
May 1, 2018: Journal of Biological Chemistry
Jean E Crabtree, Silja Wessler
Twenty-five years ago, Helicobacter pylori was identified as the causative agent of gastric disorders,ranging from acute inflammation [...].
April 26, 2018: Toxins
Shawn J Waller, Laura E Knighton, Lenora M Crabtree, Abigail L Perkins, Adam M Reitzel, Andrew W Truman
Marine organisms experience abiotic stressors such as fluctuations in temperature, UV radiation, salinity, and oxygen concentration. Heat shock proteins (HSPs) assist in the response of cells to these stressors by refolding and maintaining the activity of damaged proteins. The well-conserved Hsp70 chaperone family is essential for cell viability as well as the response to stress. Organisms possess a variety of Hsp70 isoforms that differ slightly in amino acid sequence, yet very little is known about their functional relevance...
April 25, 2018: Cell Stress & Chaperones
Sophie J Bradley, Colin Molloy, Christoffer Bundgaard, Adrian J Mogg, Karen J Thompson, Louis Dwomoh, Helen E Sanger, Michael Crabtree, Simon M Brooke, Patrick M Sexton, Christian C Felder, Arthur Christopoulos, Lisa M Broad, Andrew B Tobin, Christopher J Langmead
The realisation of the therapeutic potential of targeting the M1 muscarinic acetylcholine receptor (M1 mAChR) for the treatment of cognitive decline in Alzheimer's disease has prompted the discovery of M1 mAChR ligands showing efficacy in alleviating cognitive dysfunction in both rodents and humans. Among these is GSK1034702, described previously as a potent M1 receptor allosteric agonist, which showed pro-cognitive effects in rodents and improved immediate memory in a clinical nicotine withdrawal test but induced significant side-effects...
April 25, 2018: Molecular Pharmacology
Makoto Imura, Ryo Iwakiri, Takeshi Bamba, Eiichiro Fukusaki
The budding yeast Saccharomyces cerevisiae is an important microorganism for fermentation and the food industry. However, during production, S. cerevisiae commonly uses the ethanol fermentation pathway for glucose utilization if excess sugar is present, even in the presence of sufficient oxygen levels. This aerobic ethanol fermentation, referred to as "the Crabtree effect" is one of the most significant reasons for low cell yield. To weaken the Crabtree effect in fed-batch and continuous culture, sugar flow should be limited...
April 20, 2018: Journal of Bioscience and Bioengineering
Yanink Caro-Vega, Anna Schultze, Anne Marie W Efsen, Frank A Post, Alexander Panteleev, Aliaksandr Skrahin, Jose M Miro, Enrico Girardi, Daria N Podlekareva, Jens D Lundgren, Juan Sierra-Madero, Javier Toibaro, Jaime Andrade-Villanueva, Simona Tetradov, Jan Fehr, Joan Caylà, Marcelo H Losso, Robert F Miller, Amanda Mocroft, Ole Kirk, Brenda Crabtree-Ramírez
BACKGROUND: Efavirenz-based antiretroviral therapy (ART) regimens are preferred for treatment of adult HIV-positive patients co-infected with tuberculosis (HIV/TB). Few studies have compared outcomes among HIV/TB patients treated with efavirenz or non-efavirenz containing regimens. METHODS: HIV-positive patients aged ≥16 years with a diagnosis of tuberculosis recruited to the TB:HIV study between Jan 1, 2011, and Dec 31, 2013 in 19 countries in Eastern Europe (EE), Western Europe (WE), and Latin America (LA) who received ART concomitantly with TB treatment were included...
April 23, 2018: BMC Infectious Diseases
Elaine Crabtree, Charlotte Wilson, Rosaleen McElvaney
Despite a recent focus highlighting the systemic impact of childhood sexual abuse (CSA), the needs of nonabused siblings have been largely overlooked. This interpretative phenomenological analysis study explored the lived experience of nonabused adult siblings of survivors of CSA. Semistructured interviews were undertaken with five adult siblings who were, or had been attending a support service. Emergent themes demonstrated the personal and relational impact of CSA on siblings which were captured across five domains: trying to make sense of it all, struggling to provide support, managing the impact on the wider family, feeling silenced and finding a voice, and rescripting the future...
April 1, 2018: Journal of Interpersonal Violence
Jin Young Park, David Forman, Langgeng Agung Waskito, Yoshio Yamaoka, Jean E Crabtree
Gastric cancer is a major health burden and is the fifth most common malignancy and the third most common cause of death from cancer worldwide. Development of gastric cancer involves several aspects, including host genetics, environmental factors, and Helicobacter pylori infection. There is increasing evidence from epidemiological studies of the association of H. pylori infection and specific virulence factors with gastric cancer. Studies in animal models indicate H. pylori is a primary factor in the development of gastric cancer...
April 19, 2018: Toxins
Justine P Wu, Laura J Damschroder, Michael D Fetters, Brian J Zikmund-Fisher, Benjamin F Crabtree, Shawna V Hudson, Mack T Ruffin Iv, Juliana Fucinari, Minji Kang, L Susan Taichman, John W Creswell
BACKGROUND: Women with chronic medical conditions, such as diabetes and hypertension, have a higher risk of pregnancy-related complications compared with women without medical conditions and should be offered contraception if desired. Although evidence based guidelines for contraceptive selection in the presence of medical conditions are available via the United States Medical Eligibility Criteria (US MEC), these guidelines are underutilized. Research also supports the use of decision tools to promote shared decision making between patients and providers during contraceptive counseling...
April 18, 2018: JMIR Research Protocols
Danielle M Graef, Valerie McLaughlin Crabtree, Deo Kumar Srivastava, Chenghong Li, Michele Pritchard, Pamela S Hinds, Belinda Mandrell
OBJECTIVE: Disrupted sleep is common in pediatric cancer, which is associated with psychological distress and may impact neural recovery. Information regarding sleep during pediatric brain tumor treatment is limited. This study aimed to describe objective sleep-wake patterns and examine the sleep-mood relation in youth hospitalized for intensive chemotherapy and stem cell rescue. METHODS: Participants included 37 patients (M age =9.6 ± 4.2 years) enrolled on a medulloblastoma protocol (SJMB03) and their parents...
April 17, 2018: Psycho-oncology
Yumiko Nambu-Nishida, Keiji Nishida, Tomohisa Hasunuma, Akihiko Kondo
Kluyveromyces marxianus is a thermotolerant, crabtree-negative yeast, which preferentially directs metabolism (e.g., from the tricarboxylic acid cycle) to aerobic alcoholic fermentation. Thus K. marxianus has great potential for engineering to produce various materials under aerobic cultivation conditions. In this study, we engineered K. marxianus to produce and secrete a single-chain antibody (scFv), a product that is highly valuable but has historically proven difficult to generate at large scale. scFv production was obtained with strains carrying either plasmid-borne or genomically integrated constructs using various combinations of promoters (P MDH1 or P ACO1 ) and secretion signal peptides (KmINUss or Scα-MFss)...
April 12, 2018: AMB Express
Carlos A Hinojosa, Ana E Nunez-Salgado, Javier E Anaya-Ayala, Hugo Laparra-Escareno, Laura J Ortiz-Lopez, Jaime O Herrera-Caceres, Brenda E Crabtree-Ramirez, Juan G Sierra-Madero
Objectives The longer survival of patients with human immunodeficiency virus/acquired immunodeficiency syndrome and the introduction of the highly active antiretroviral therapy have increased the number of chronic conditions; among these, cardiovascular diseases. The aim of this study is to determine patient, disease, and factors associated with peripheral arterial disease in a population of patients with human immunodeficiency virus/acquired immunodeficiency syndrome. Methods A prospective nested case-control study of a cohort of patients with human immunodeficiency virus/acquired immunodeficiency syndrome was conducted in a tertiary medical center in Mexico City...
January 1, 2018: Vascular
Adrian J Mogg, Thomas Eessalu, Megan Johnson, Rebecca Wright, Helen E Sanger, Hongling Xiou, Michael Crabtree, Alex Smith, Ellen Colvin, Douglas Schober, Donald Gehlert, Cynthia Jesudason, Paul Goldsmith, Michael P Johnson, Christian C Felder, Vanessa N Barth, Lisa M Broad
In the search for improved symptomatic treatment options for neurodegenerative and neuropsychiatric diseases, muscarinic acetylcholine M1 receptors (M1 mAChRs) have received significant attention. Drug development efforts have identified a number of novel ligands, some of which have advanced to the clinic. However, a significant issue for progressing these therapeutics is the lack of robust, translatable and validated biomarkers. One valuable approach to assessing target engagement is to utilize PET tracers...
April 11, 2018: Journal of Pharmacology and Experimental Therapeutics
Gillian Douglas, Ashley B Hale, Jyoti Patel, Surawee Chuaiphichai, Ayman Al Haj Zen, Victoria S Rashbrook, Lucy Trelfa, Mark J Crabtree, Eileen McNeill, Keith M Channon
Introduction: GTP cyclohydrolase I (GTPCH) catalyses the first and rate-limiting reaction in the synthesis of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthases (NOS). Both eNOS and iNOS have been implicated in the progression of atherosclerosis, with opposing effects in eNOS and iNOS knockout mice. However, the pathophysiologic requirement for BH4 in regulating both eNOS and iNOS function, and the effects of loss of BH4 on the progression of atherosclerosis remains unknown...
March 27, 2018: Cardiovascular Research
Angela Hassiotis, Michaela Poppe, Andre Strydom, Victoria Vickerstaff, Ian Hall, Jason Crabtree, Rumana Omar, Michael King, Rachael Hunter, Alessandro Bosco, Asit Biswas, Victoria Ratti, Jessica Blickwedel, Vivien Cooper, William Howie, Mike Crawford
BACKGROUND: Preliminary studies have indicated that training staff in Positive Behaviour Support (PBS) may help to reduce challenging behaviour among people with intellectual disability (ID). OBJECTIVE: To evaluate whether or not such training is clinically effective in reducing challenging behaviour in routine care. The study also included longer-term follow-up (approximately 36 months). DESIGN: A multicentre, single-blind, two-arm, parallel-cluster randomised controlled trial...
March 2018: Health Technology Assessment: HTA
Benjamin Z Stanton, Emma J Chory, Gerald R Crabtree
Proximity, or the physical closeness of molecules, is a pervasive regulatory mechanism in biology. For example, most posttranslational modifications such as phosphorylation, methylation, and acetylation promote proximity of molecules to play deterministic roles in cellular processes. To understand the role of proximity in biologic mechanisms, chemical inducers of proximity (CIPs) were developed to synthetically model biologically regulated recruitment. Chemically induced proximity allows for precise temporal control of transcription, signaling cascades, chromatin regulation, protein folding, localization, and degradation, as well as a host of other biologic processes...
March 9, 2018: Science
Olga Tymejczyk, Ellen Brazier, Constantin Yiannoutsos, Kara Wools-Kaloustian, Keri Althoff, Brenda Crabtree-Ramírez, Kinh Van Nguyen, Elizabeth Zaniewski, Francois Dabis, Jean d'Amour Sinayobye, Nanina Anderegg, Nathan Ford, Radhika Wikramanayake, Denis Nash
BACKGROUND: The effect of antiretroviral treatment (ART) eligibility expansions on patient outcomes, including rates of timely ART initiation among those enrolling in care, has not been assessed on a large scale. In addition, it is not known whether ART eligibility expansions may lead to "crowding out" of sicker patients. METHODS AND FINDINGS: We examined changes in timely ART initiation (within 6 months) at the original site of HIV care enrollment after ART eligibility expansions among 284,740 adult ART-naïve patients at 171 International Epidemiology Databases to Evaluate AIDS (IeDEA) network sites in 22 countries where national policies expanding ART eligibility were introduced between 2007 and 2015...
March 2018: PLoS Medicine
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