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Gitte Berkers, Peter van Mourik, Annelotte M Vonk, Evelien Kruisselbrink, Johanna F Dekkers, Karin M de Winter-de Groot, Hubertus G M Arets, Rozemarijn E P Marck-van der Wilt, Jasper S Dijkema, Maaike M Vanderschuren, Roderick H J Houwen, Harry G M Heijerman, Eduard A van de Graaf, Sjoerd G Elias, Christof J Majoor, Gerard H Koppelman, Jolt Roukema, Marleen Bakker, Hettie M Janssens, Renske van der Meer, Robert G J Vries, Hans C Clevers, Hugo R de Jonge, Jeffrey M Beekman, Cornelis K van der Ent
In vitro drug tests using patient-derived stem cell cultures offer opportunities to individually select efficacious treatments. Here, we provide a study that demonstrates that in vitro drug responses in rectal organoids from individual patients with cystic fibrosis (CF) correlate with changes in two in vivo therapeutic endpoints. We measured individual in vitro efficaciousness using a functional assay in rectum-derived organoids based on forskolin-induced swelling and studied the correlation with in vivo effects...
February 12, 2019: Cell Reports
Thomas H Thatcher, Collynn F Woeller, Claire E McCarthy, Patricia J Sime
Exposure to air pollution and other environmental inhalation hazards, such as occupational exposures to dusts and fumes, aeroallergens, and tobacco smoke, is a significant cause of chronic lung inflammation leading to respiratory disease. It is now recognized that resolution of inflammation is an active process controlled by a novel family of small lipid mediators termed "specialized pro-resolving mediators" or SPMs, derived mainly from dietary omega-3 polyunsaturated fatty acids. Chronic inflammation results from an imbalance between pro-inflammatory and pro-resolution pathways...
February 10, 2019: Pharmacology & Therapeutics
Ahmed M Elmansi, Mohamed E Awad, Nada H Eisa, Dmitry Kondrikov, Khaled A Hussein, Alexandra Aguilar-Pérez, Samuel Herberg, Sudharsan Periyasamy-Thandavan, Sadanand Fulzele, Mark W Hamrick, Meghan E McGee-Lawrence, Carlos M Isales, Brian F Volkman, William D Hill
Dipeptidyl peptidase 4 (DPP4) is an exopeptidase found either on cell surfaces where it is highly regulated in terms of its expression and surface availability (CD26) or in a free/circulating soluble constitutively available and intrinsically active form. It is responsible for proteolytic cleavage of many peptide substrates. In this review we discuss the idea that DPP4-cleaved peptides are not necessarily inactivated, but rather can possess either a modified receptor selectivity, modified bioactivity, new antagonistic activity, or even a novel activity relative to the intact parent ligand...
February 10, 2019: Pharmacology & Therapeutics
Raquel F Guedes-Monteiro, Leticia V R Franco, Bruno S Moda, Alexander Tzagoloff, Mário H Barros
Mitochondrial tRNAs are processed at their 5'ends by highly divergent but ubiquitous RNase P. In Saccharomyces cerevisiae, Rpm2p is the protein component of RNase P. Here, we identify four novel genes MTA1, MTA2, GEP5 and PET130 of the Saccharomycetaceae family that are necessary for an efficient processing of mitochondrial tRNAs. Null mutants of mta1, mta2 and gep5 have severely reduced levels of mitochondrial tRNAs; in addition, temperature sensitive (ts) mutants of mta1, mta2, pet130 and gep5 accumulated tRNAs precursor transcripts at the restrictive but not at the permissive temperature...
February 10, 2019: Biochimica et biophysica acta. Molecular cell research
Guixia Hao, Susan McCormick, Martha Vaughan, Todd Naumann, Hye-Seon Kim, Robert H Proctor, Amy Kelly, Todd Ward
Fusarium head blight (FHB) of wheat and barley caused by the fungus Fusarium graminearum reduces crop yield and contaminates grain with mycotoxins. In this study, we investigated two exo-1, 5-α-L-arabinanases (Arb93A and Arb93B) secreted by F. graminearum, and their effect on wheat head blight development. Arabinan is an important component of plant cell walls, but it was not known if these arabinanases play a role in FHB. Both ARB93A and ARB93B were induced during the early stages of infection. arb93A mutants did not exhibit a detectable change in ability to cause FHB, whereas, arb93B mutants caused lower levels of FHB symptoms and deoxynivalenol contamination compared to the wild type...
February 13, 2019: Molecular Plant-microbe Interactions: MPMI
Dan-Qing Yu, Ping-Ping Lv, Yi-Shang Yan, Guan-Xin Xu, Annapurna Sadhukhan, Shan Dong, Yan Shen, Jun Ren, Xue-Ying Zhang, Chun Feng, Yi-Ting Huang, Shen Tian, Yin Zhou, Yi-Ting Cai, Zhen-Hua Ming, Guo-Lian Ding, Hong Zhu, Jian-Zhong Sheng, Min Jin, He-Feng Huang
Brown adipose tissue (BAT) is an exclusive tissue of nonshivering thermogenesis. It is fueled by lipids and glucose and involved in energy and metabolic homeostasis. Intrauterine exposure to hyperglycemia during gestational diabetes mellitus may result in abnormal fetal development and metabolic phenotypes in adulthood. However, whether intrauterine hyperglycemia influences the development of BAT is unknown. In this study, mouse embryos were exposed to the intrauterine hyperglycemia environment by injecting streptozocin into pregnant mice at 1 d post coitum (dpc)...
February 13, 2019: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Veronique Gouverneur, Robert Szpera, Daniel F J Moseley, Lewis B Smith, Alistair J Sterling
This Review summarizes the advances in fluorination via C(sp2)-H and C(sp3)-H activation. Transition metal catalyzed approaches championed by palladium have allowed the installation of a fluorine substituent at C(sp2) and C(sp3) sites exploiting the reactivity of high oxidation transition metal fluoride complexes combined with the use of directing group (some transient) to control regio- and stereoselectivity. The large majority of known methods employ electrophilic fluorination reagents, but methods combining a nucleophilic fluoride source with an oxidant have appeared...
February 13, 2019: Angewandte Chemie
Chintan K Gandhi, Romel Holmes, Ira H Gewolb, Bruce D Uhal
BACKGROUND: Pancreatic digestive enzymes present in meconium might be responsible for meconium-induced lung injury. The local Renin Angiotensin System plays an important role in lung injury and inflammation. Particularly, angiotensin converting enzyme-2 (ACE-2) has been identified as a protective lung enzyme against the insult. ACE-2 converts pro-apoptotic Angiotensin II to anti-apoptotic Angiotensin 1-7. However, the effect of meconium on ACE-2 has never been studied before. OBJECTIVE: To study the effect of meconium on ACE-2, and whether inhibition of proteolytic enzymes present in the meconium reverses its effects on ACE-2...
February 13, 2019: Lung
Jessica F Wilhelm, Daniel J Bain, Mark B Green, Kathleen F Bush, William H McDowell
Mobilization of trace metals from soils to surface waters can impact both human and ecosystem health. This study resamples a water sample archive to explore the spatial pattern of streamwater total concentrations of arsenic, cadmium, copper, lead, and zinc and their associations with biogeochemical controls in northern New England. Road deicing appears to result in elevated trace metal concentrations, as trace metal concentrations are strongly related to sodium concentrations and are most elevated when the sodium: chloride ratio is near 1...
2019: PloS One
Francois Kiemde, Massa Dit Achille Bonko, Marc Christian Tahita, Petra F Mens, Halidou Tinto, Henk D F H Schallig, Michael Boele van Hensbroek
BACKGROUND: Malaria rapid diagnostic tests (RDT) have limitations due to the persistence of histidine-rich protein 2 (HRP2) antigen after treatment and low sensitivity of Plasmodium lactate dehydrogenase (pLDH) based RDTs. To improve the diagnosis of malaria in febrile children, two diagnostic algorithms, based on sequential interpretation of a malaria rapid diagnostic test detecting two different targets of Plasmodium species and followed by expert microscopy, were evaluated. METHODS: Two diagnostic algorithms were evaluated using 407 blood samples collected between April and October 2016 from febrile children and the diagnostic accuracy of both algorithms was determined...
2019: PloS One
Katia R Vaz de Azevedo, Cristiane B Lopes, Rosana H T L R Andrade, Fernanda F N Pacheco da Costa, Lúcio S Gonçalves, Rachel Medeiros Dos Santos, Flávio R F Alves
INTRODUCTION: The study aimed to evaluate, through in vivo tomographic analysis, the prevalence of C-shaped canals in mandibular first and second molars of Brazilian individuals, analyzing its frequency by thirds of the roots, and in contralateral teeth. METHODS: Images of 801 mandibular molars (379 first molars and 422 second molars) from 334 Brazilian individuals (142 men and 192 women) were identified through 1544 cone beam computed tomography (CBCT) exams, obtained from a private oral radiologic clinic...
2019: PloS One
Nadine Ferris France, Stephen H-F Macdonald, Ronan R Conroy, Patrick Chiroro, Deirdre Ni Cheallaigh, Masimba Nyamucheta, Bekezela Mapanda, Godsway Shumba, Dennis Mudede, Elaine Byrne
INTRODUCTION: Self-stigma-negative self-judgements resulting in shame, worthlessness and self-blame-may play a crucial role in emotional reactions and cause emotional distress among many people living with HIV and other chronic illnesses. Furthermore, self-stigma negatively impacts on self-agency, quality of life, adherence to treatment, and access to services. High levels of self-stigma have been reported across many countries, however few programmes or interventions exist to specifically tackle this phenomenon...
2019: PloS One
William A E Parker, Rachel C Orme, Jessica Hanson, Hannah M Stokes, Claire M Bridge, Patricia A Shaw, Wael Sumaya, Kirstie Thorneycroft, Giovanna Petrucci, Benedetta Porro, Heather M Judge, Ramzi A Ajjan, Bianca Rocca, Robert F Storey
Higher aspirin doses may be inferior in ticagrelor-treated acute coronary syndrome (ACS) patients and reducing bleeding risk whilst maintaining antithrombotic benefits could improve outcomes. We characterized the pharmacodynamics of a novel dual-antiplatelet-therapy regimen consisting of very-low-dose twice-daily (BD) aspirin with standard-dose ticagrelor. A total of 20 ticagrelor-treated ACS patients entered a randomized crossover to take aspirin 20 mg BD (12-hourly) during one 14-day period and 75 mg once-daily (OD) in the other...
February 13, 2019: Platelets
Nan He, Bradley H Rosen, Jaimie S Gray, Idil A Evans, Marina Zieger, Ziying Yan, Florie Borel, Bo Liang, Xingshen Sun, Shashanna R Moll, Michael H Brodsky, Christian Mueller, John F Engelhardt
RATIONALE: The most prevalent genetic cause of chronic obstructive pulmonary disease is alpha-1 antitrypsin (A1AT) deficiency, a disorder that has yet to be widely modeled in animals because of species-specific differences between rodents and humans. OBJECTIVES: To address these challenges, we engineered two A1AT ferret models using zygote gene editing to test the hypothesis that unopposed protease activity within the lung leads to emphysema and bronchitis. METHODS: Guide RNAs targeting exon 2 (for knockout) and exon 5 (for Z-allele mutation, Pi*Z) of the ferret A1AT gene were injected into ferret zygotes with Cas9 mRNA...
December 2018: Annals of the American Thoracic Society
Bárbara E Souza, Marcelo H F Ottoni, Priscila G M de Alvarenga, Agnes Batista Meireles, João V W Silveira, Valéria Gomes Almeida, Michaelle G Dos Santos, Libardo Andrés González-Torres, Cristiane F Fuzer Grael, Gustavo Eustáquio Alvim Brito-Melo, Bethânia A Avelar-Freitas
Agareratum fastigiatum is a Brazilian medicinal plant used as anti-inflammaroty and for wound healing by the folk medicine. In vitro and in vivo studies involving A. fastigiatum essential oil (EOAF) showed indications of anti-inflammatory activity, however, its effect on membrane integrins involved on cell migration is still unclear. Hence, it was evaluated in the present study the effect of EOAF on CD18 frequency on human lymphocytes. By using gas chromatography/mass spectrometry it was identified 9 compounds on EOAF: α-pinene; β-pinene; β-myrcene; d-limonene; β-ocimene; sesquiterpenes; α-copaene; 4,8-β-epóxi-caryophyllene; germacrene and bicyclogermacrene...
February 13, 2019: Natural Product Research
Manish Sharma, Daniel Sethio, Latévi Max Lawson Daku, Hans Hagemann
The closoborane and their derivatives have attracted high interest owing to their superionic conductivity. Very recently, high ionic conductivities have been reported for compounds containing the closoborane ion B12 H12 2- . In this work, we address halogen substituted ions B12 Hn X12-n 2- (n = 0-3, 6, 9-12 and X = F, Cl, Br) using DFT calculations to probe the structures, the chemical stability and the electrochemical stability as well as spectroscopic properties in view of potential future applications. Considering the theoretical reaction n/12 B12 H12 2- + (12-n)/12 B12 X12 2- --> B12 Hn X12-n 2- , it appears that for X = Cl and Br the compounds with n=6 are stabilized by about 100kJ/mol...
February 13, 2019: Journal of Physical Chemistry. A
M B Maina, M G Yunusa, A M Bukar, U Ahmad, A T Salihu, H A Ibrahim, A Muhammad, S K Hamidu, A U Yaro, M A Awadelkareem, F E Nasr, T Baden
No abstract text is available yet for this article.
February 13, 2019: European Journal of Neuroscience
Caroline P Adrian, Kevin K Haussler, Christopher E Kawcak, Raoul F Reiser, Cheryl Riegger-Krugh, Ross H Palmer, C Wayne McIlwraith, Robert A Taylor
OBJECTIVE: Identify relevant electromyography (EMG), kinematic, and kinetic changes resulting from monopolar radiofrequency energy (MRFE)-induced cranial cruciate ligament (CCL) injury and eventual rupture in dogs. STUDY DESIGN: Experimental, repeated measures. ANIMALS: Five purpose-bred female dogs free of orthopedic and neurologic disease. METHODS: Surface EMG, joint kinematics, and ground reaction forces were assessed at a trot in the pelvic limbs at baseline, at 2 and 4 weeks after unilateral MRFE-induced CCL injury, and at 4, 8, and 16 weeks after CCL rupture (CCLR)...
February 13, 2019: Veterinary Surgery: VS
G San Blas, F M Silva Dias, A Specht, M Martins Casagrande, O H Hendrik Mielke
Feltia llanoi (Köhler, 1953) stat. rev. and its hitherto senior subjective synonym Feltia brachystria (Hampson, 1903) are two species of noctuid moths with unusual broadly bipectinate antenna and restricted distribution in central eastern Argentina, southern Brazil, and Uruguay. Examination of the type of specimens and further material from several collections indicates that these names are not synonyms, but valid species, and reveal the occurrence of F. llanoistat. rev. in Brazil. Therefore, F. llanoistat...
February 13, 2019: Neotropical Entomology
H Dralle, F Weber
No abstract text is available yet for this article.
February 13, 2019: Der Chirurg; Zeitschrift Für Alle Gebiete der Operativen Medizen
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