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https://www.readbyqxmd.com/read/28052200/structure-activity-relationship-of-the-antimalarial-ozonide-artefenomel-oz439
#1
Yuxiang Dong, Xiaofang Wang, Sriraghavan Kamaraj, Vivek J Bulbule, Francis C K Chiu, Jacques Chollet, Manickam Dhanasekaran, Christopher D Hein, Petros Papastogiannidis, Julia Morizzi, David M Shackleford, Helena Barker, Eileen Ryan, Christian Scheurer, Yuanqing Tang, Qingjie Zhao, Lin Zhou, Karen L White, Heinrich Urwyler, William N Charman, Hugues Matile, Sergio Wittlin, Susan A Charman, Jonathan L Vennerstrom
Building on insights gained from the discovery of the antimalarial ozonide arterolane (OZ277), we now describe the structure-activity relationship (SAR) of the antimalarial ozonide artefenomel (OZ439). Primary and secondary amino ozonides had higher metabolic stabilities than tertiary amino ozonides, consistent with their higher pKa and lower log D7.4 values. For primary amino ozonides, addition of polar functional groups decreased in vivo antimalarial efficacy. For secondary amino ozonides, additional functional groups had variable effects on metabolic stability and efficacy, but the most effective members of this series also had the highest log D7...
January 18, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27984662/long-term-structural-and-biomass-dynamics-of-virgin-tsuga-canadensis-pinus-strobus-forests-after-hurricane-disturbance
#2
Anthony W D'Amato, David A Orwig, David R Foster, Audrey Barker Plotkin, Peter K Schoonmaker, Maggie R Wagner
The development of old-growth forests in northeastern North America has largely been within the context of gap-scale disturbances given the rarity of stand-replacing disturbances. Using the 10-ha old-growth Harvard Tract and its associated 90-year history of measurements, including detailed surveys in 1989 and 2009, we document the long-term structural and biomass development of an old-growth Tsuga canadensis-Pinus strobus forest in southern New Hampshire, USA following a stand-replacing hurricane in 1938. Measurements of aboveground biomass pools were integrated with data from second- and old-growth T...
December 16, 2016: Ecology
https://www.readbyqxmd.com/read/27979592/synthesis-and-antiproliferative-activity-of-2-chlorophenyl-carboxamide-thienopyridines
#3
Michelle van Rensburg, Euphemia Leung, Natalie A Haverkate, Chatchakorn Eurtivong, Lisa I Pilkington, J├│hannes Reynisson, David Barker
3-Amino-2-arylcarboxamide-thieno[2,3-b]pyridines are a known class of antiproliferative compounds with activity against the phospholipase C enzyme. To further investigate the structure activity relationships of these derivatives a series of analogues were prepared modifying key functional groups. It was determined that modification of the 3-amino and 2-aryl carboxamide functionalities resulted in complete elimination of activity, whilst modification at C-5 allowed compounds of greater activity to be prepared...
January 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27977294/house-dust-endotoxin-levels-are-associated-with-adult-asthma-in-a-u-s-farming-population
#4
Megan Ulmer Carnes, Jane A Hoppin, Nervana Metwali, Annah B Wyss, John L Hankinson, Elizabeth Long O'Connell, Marie Richards, Stuart Long, Laura E Beane Freeman, Dale P Sandler, Paul K Henneberger, Christie Barker-Cummings, David M Umbach, Peter S Thorne, Stephanie J London
RATIONALE: Endotoxin initiates a pro-inflammatory response from the innate immune system. Studies in children suggest endotoxin exposure from house dust may be an important risk factor for asthma, but few studies have been conducted in adult populations. OBJECTIVES: To investigate the association of house dust endotoxin levels with asthma and related phenotypes (wheeze, atopy, and pulmonary function) in a large U.S. farming population. METHODS: Dust was collected from the bedrooms (n=2,485) of participants enrolled in a case-control study of current asthma (927 cases) nested within the Agricultural Health Study...
December 15, 2016: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/27940449/next-generation-sequencing-of-circulating-cell-free-dna-for-evaluating-mutations-and-gene-amplification-in-metastatic-breast-cancer
#5
Karen Page, David S Guttery, Daniel Fernandez-Garcia, Allison Hills, Robert K Hastings, Jinli Luo, Kate Goddard, Vedia Shahin, Laura Woodley-Barker, Brenda M Rosales, R Charles Coombes, Justin Stebbing, Jacqueline A Shaw
BACKGROUND: Breast cancer tissues are heterogeneous and show diverse somatic mutations and somatic copy number alterations (CNAs). We used a novel targeted next generation sequencing (NGS) panel to examine cell-free DNA (cfDNA) to detect somatic mutations and gene amplification in women with metastatic breast cancer (MBC). METHODS: cfDNA from pretreated patients (n = 42) and 9 healthy controls were compared with matched lymphocyte DNA by NGS, using a custom 158 amplicon panel covering hot-spot mutations and CNAs in 16 genes, with further validation of results by droplet digital PCR...
December 9, 2016: Clinical Chemistry
https://www.readbyqxmd.com/read/27940388/the-impact-of-sleep-and-psychiatric-symptoms-on-alcohol-consequences-among-young-adults
#6
Mary Beth Miller, Eliza Van Reen, David H Barker, Brandy M Roane, Brian Borsari, John E McGeary, Ronald Seifer, Mary A Carskadon
OBJECTIVE: Independent lines of research have documented links between psychiatric symptoms and poor sleep quality, psychiatric symptoms and alcohol use, and alcohol use and poor sleep quality. The current study examined the synergistic effect of poor sleep quality and psychiatric symptoms on alcohol-related consequences in heavy-drinking young adults. METHOD: Matriculating college students reporting at least one heavy drinking episode over the first nine weeks of the semester (N=385, 52% female) were categorized as experiencing 'good' (n=280) versus 'poor' sleep quality (n=105) and screening 'positive' (n=203) or 'negative' (n=182) for a psychiatric disorder...
March 2017: Addictive Behaviors
https://www.readbyqxmd.com/read/27918078/nuclear-ca-2-signalling-in-arbuscular-mycorrhizal-and-actinorhizal-endosymbioses-on-the-trail-of-novel-underground-signals
#7
REVIEW
David G Barker, Mireille Chabaud, Guilia Russo, Andrea Genre
I. II. III. IV. References SUMMARY: Root endosymbioses are beneficial associations formed between terrestrial plants and either bacterial or fungal micro-organisms. A common feature of these intracellular symbioses is the requirement for mutual recognition between the two partners before host-regulated microbial entry. As part of this molecular dialogue, symbiosis-specific microbial factors set in motion a highly conserved plant signal transduction pathway, of which a central component is the activation of sustained nuclear Ca(2+) oscillations in target cells of the host epidermis...
December 5, 2016: New Phytologist
https://www.readbyqxmd.com/read/27910188/comparing-rewarding-and-reinforcing-properties-between-bath-salt-3-4-methylenedioxypyrovalerone-mdpv-and-cocaine-using-ultrasonic-vocalizations-in-rats
#8
Steven J Simmons, Ryan A Gregg, Fionya H Tran, Lili Mo, Eva von Weltin, David J Barker, Taylor A Gentile, Lucas R Watterson, Scott M Rawls, John W Muschamp
Abuse of synthetic psychostimulants like synthetic cathinones has risen in recent years. 3,4-Methylenedioxypyrovalerone (MDPV) is one such synthetic cathinone that demonstrates a mechanism of action similar to cocaine. Compared to cocaine, MDPV is more potent at blocking dopamine and norepinephrine reuptake and is readily self-administered by rodents. The present study compared the rewarding and reinforcing properties of MDPV and cocaine using systemic injection dose-response and self-administration models...
December 1, 2016: Addiction Biology
https://www.readbyqxmd.com/read/27894631/elderly-woman-with-altered-mental-status-and-hypoxia
#9
Rebecca A Martin, David Wharton, Chad Barker, Claudia D Haivas, Berneet Kaur, Jessica Whittle
No abstract text is available yet for this article.
December 2016: Annals of Emergency Medicine
https://www.readbyqxmd.com/read/27889361/adult-bronchiectasis-patients-a-first-look-at-the-united-states-bronchiectasis-research-registry
#10
Timothy R Aksamit, Anne E O'Donnell, Alan Barker, Kenneth N Olivier, Kevin L Winthrop, M Leigh Anne Daniels, Margaret Johnson, Edward Eden, David Griffith, Michael Knowles, Mark Metersky, Matthias Salathe, Byron Thomashow, Gregory Tino, Gerard Turino, Betsy Carretta, Charles L Daley
OBJECTIVE: We sought to describe the characteristics of adult bronchiectasis patients enrolled in the United States Bronchiectasis Research Registry (BRR). METHODS: The BRR is a database of non-cystic fibrosis bronchiectasis (NCFB) patients enrolled at 13 sites within the United States. Baseline demographic, spirometric, imaging, microbiologic, and therapeutic data were entered into a central web-based database. Patients were subsequently analyzed by the presence NTM...
November 23, 2016: Chest
https://www.readbyqxmd.com/read/27845237/early-life-farm-exposures-and-adult-asthma-and-atopy-in-the-agricultural-lung-health-study
#11
John S House, Annah B Wyss, Jane A Hoppin, Marie Richards, Stuart Long, David M Umbach, Paul K Henneberger, Laura E Beane Freeman, Dale P Sandler, Elizabeth Long O'Connell, Christie Barker-Cummings, Stephanie J London
BACKGROUND: Previous studies, mostly from Europe, suggest that early-life farming exposures protect against childhood asthma and allergy; few data exist on asthma and allergy in adults. OBJECTIVE: We sought to examine associations between early-life farming exposures and current asthma and atopy in an older adult US farming population. METHODS: We analyzed data from 1746 farmers and 1555 spouses (mean age, 63) from a case-control study nested within the Agricultural Health Study...
November 12, 2016: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/27834372/the-pangenome-of-an-agronomically-important-crop-plant-brassica-oleracea
#12
Agnieszka A Golicz, Philipp E Bayer, Guy C Barker, Patrick P Edger, HyeRan Kim, Paula A Martinez, Chon Kit Kenneth Chan, Anita Severn-Ellis, W Richard McCombie, Isobel A P Parkin, Andrew H Paterson, J Chris Pires, Andrew G Sharpe, Haibao Tang, Graham R Teakle, Christopher D Town, Jacqueline Batley, David Edwards
There is an increasing awareness that as a result of structural variation, a reference sequence representing a genome of a single individual is unable to capture all of the gene repertoire found in the species. A large number of genes affected by presence/absence and copy number variation suggest that it may contribute to phenotypic and agronomic trait diversity. Here we show by analysis of the Brassica oleracea pangenome that nearly 20% of genes are affected by presence/absence variation. Several genes displaying presence/absence variation are annotated with functions related to major agronomic traits, including disease resistance, flowering time, glucosinolate metabolism and vitamin biosynthesis...
November 11, 2016: Nature Communications
https://www.readbyqxmd.com/read/27812161/a-deterministic-model-to-quantify-risk-and-guide-mitigation-strategies-to-reduce-bluetongue-virus-transmission-in-california-dairy-cattle
#13
Christie Mayo, Courtney Shelley, N James MacLachlan, Ian Gardner, David Hartley, Christopher Barker
The global distribution of bluetongue virus (BTV) has been changing recently, perhaps as a result of climate change. To evaluate the risk of BTV infection and transmission in a BTV-endemic region of California, sentinel dairy cows were evaluated for BTV infection, and populations of Culicoides vectors were collected at different sites using carbon dioxide. A deterministic model was developed to quantify risk and guide future mitigation strategies to reduce BTV infection in California dairy cattle. The greatest risk of BTV transmission was predicted within the warm Central Valley of California that contains the highest density of dairy cattle in the United States...
2016: PloS One
https://www.readbyqxmd.com/read/27805026/adenovirally-induced-polyfunctional-t-cells-do-not-necessarily-recognize-the-infected-target-lessons-from-a-phase-i-trial-of-the-aeras-402-vaccine
#14
Melissa Nyendak, Gwendolyn M Swarbrick, Amanda Duncan, Meghan Cansler, Ervina Winata Huff, David Hokey, Tom Evans, Lewellys Barker, Gretta Blatner, Jerald Sadoff, Macaya Douoguih, Maria Grazia Pau, Deborah A Lewinsohn, David M Lewinsohn
The development of a vaccine for Mycobacterium tuberculosis (Mtb) has been impeded by the absence of correlates of protective immunity. One correlate would be the ability of cells induced by vaccination to recognize the Mtb-infected cell. AERAS-402 is a replication-deficient serotype 35 adenovirus containing DNA expressing a fusion protein of Mtb antigens 85A, 85B and TB10.4. We undertook a phase I double-blind, randomized placebo controlled trial of vaccination with AERAS-402 following BCG. Analysis of the vaccine-induced immune response revealed strong antigen-specific polyfunctional CD4(+) and CD8(+) T cell responses...
November 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27799297/neuroendocrine-abnormalities-in-parkinson-s-disease
#15
REVIEW
Eduardo De Pablo-Fernández, David P Breen, Pierre M Bouloux, Roger A Barker, Thomas Foltynie, Thomas T Warner
Neuroendocrine abnormalities are common in Parkinson's disease (PD) and include disruption of melatonin secretion, disturbances of glucose, insulin resistance and bone metabolism, and body weight changes. They have been associated with multiple non-motor symptoms in PD and have important clinical consequences, including therapeutics. Some of the underlying mechanisms have been implicated in the pathogenesis of PD and represent promising targets for the development of disease biomarkers and neuroprotective therapies...
October 31, 2016: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/27797978/what-factors-predict-length-of-stay-in-a-neonatal-unit-a-systematic-review
#16
Sarah E Seaton, Lisa Barker, David Jenkins, Elizabeth S Draper, Keith R Abrams, Bradley N Manktelow
OBJECTIVE: In the UK, 1 in 10 babies require specialist neonatal care. This care can last from hours to months depending on the need of the baby. The increasing survival of very preterm babies has increased neonatal care resource use. Evidence from multiple studies is crucial to identify factors which may be important for predicting length of stay (LOS). The ability to predict LOS is vital for resource planning, decision-making and parent counselling. The objective of this review was to identify which factors are important to consider when predicting LOS in the neonatal unit...
October 18, 2016: BMJ Open
https://www.readbyqxmd.com/read/27791373/enantioselective-synthesis-of-2-3-disubstituted-benzomorpholines-analogues-of-lignan-natural-products
#17
Eun-Kyung Jung, Lisa I Pilkington, David Barker
The enantioselective synthesis of 2,3-disubstituted benzomorpholines, analogues of 1,4-benzodioxane natural products, has been achieved via addition of electron-rich aromatic donors to acyl-iminium ions derived from benzomorpholine aminols. Subsequent modification of the benzomorpholine scaffold allows side chains mimicking those found in 1,4-benzodioxane lignans to be added. Antiproliferative testing of the prepared analogues showed promising results against MDA-MB-231 and HCT116 cancer cell lines.
December 2, 2016: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/27789514/effectiveness-of-alternative-listening-devices-to-conventional-hearing-aids-for-adults-with-hearing-loss-a-systematic-review-protocol
#18
David W Maidment, Alex B Barker, Jun Xia, Melanie A Ferguson
INTRODUCTION: Hearing loss is a major public health concern, affecting over 11 million people in the UK. While hearing aids are the most common clinical intervention for hearing loss, the majority of people that would benefit from using hearing aids do not take them up. Recent technological advances have led to a rapid increase of alternative listening devices to conventional hearing aids. These include hearing aids that can be customised using a smartphone, smartphone-based 'hearing aid' apps, personal sound amplification products and wireless hearing products...
October 27, 2016: BMJ Open
https://www.readbyqxmd.com/read/27774781/fetal-programming-of-neuropsychiatric-disorders
#19
REVIEW
Gavino Faa, Mirko Manchia, Roberta Pintus, Clara Gerosa, Maria Antonietta Marcialis, Vassilios Fanos
Starting from the Developmental Origins of Health and Disease (DOHaD) hypotheses proposed by David Barker, namely fetal programming, in the past years, there is a growing evidence of the major role played by epigenetic factors during the intrauterine life and the perinatal period. Furthermore, it has been assessed that these factors can affect the health status in infancy and even in adulthood. In this review, we focus our attention on the fetal programming of the brain, analyzing the most recent literature concerning the epigenetic factors that can influence the development of neuropsychiatric disorders such as bipolar disorders, major depressive disorders, and schizophrenia...
September 2016: Birth Defects Research. Part C, Embryo Today: Reviews
https://www.readbyqxmd.com/read/27739678/evidence-of-lipid-exchange-in-styrene-maleic-acid-lipid-particle-smalp-nanodisc-systems
#20
Gavin Hazell, Thomas Arnold, Robert D Barker, Luke A Clifton, Nina-Juliane Steinke, Cecilia Tognoloni, Karen J Edler
Styrene-alt-maleic acid lipid particles (SMALPs) are self-assembled discoidal structures composed of a polymer belt and a segment of lipid bilayer, which are capable of encapsulating membrane proteins directly from the cell membrane. Here we present evidence of the exchange of lipids between such "nanodiscs" and lipid monolayers adsorbed at either solid-liquid or air-liquid interfaces. This behavior has important implications for the potential uses of nanodiscs.
November 15, 2016: Langmuir: the ACS Journal of Surfaces and Colloids
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