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Bruno Stieger, Bruno Hagenbuch
Cells need to strictly control their internal milieu, a function which is performed by the plasma membrane. Selective passage of molecules across the plasma membrane is controlled by transport proteins. As the liver is the central organ for drug metabolism, hepatocytes are equipped with numerous drug transporters expressed at the plasma membrane. Drug disposition includes absorption, distribution, metabolism, and elimination of a drug and hence multiple passages of drugs and their metabolites across membranes...
2016: F1000Research
Stevan W Djuric, Charles W Hutchins, Nari N Talaty
This review covers recent advances in the implementation of enabling chemistry technologies into the drug discovery process. Areas covered include parallel synthesis chemistry, high-throughput experimentation, automated synthesis and purification methods, flow chemistry methodology including photochemistry, electrochemistry, and the handling of "dangerous" reagents. Also featured are advances in the "computer-assisted drug design" area and the expanding application of novel mass spectrometry-based techniques to a wide range of drug discovery activities...
2016: F1000Research
Christopher J Berg, Jonathan D Kaunitz
The ability of humans to sense chemical signals in ingested substances is implicit in the ability to detect the five basic tastes; sweet, sour, bitter, salty, and umami. Of these, sweet, bitter, and umami tastes are detected by lingual G-protein-coupled receptors (GPCRs). Recently, these receptors were also localized to the gut mucosa. In this review, we will emphasize recent advances in the understanding of the mechanisms and consequences of foregut luminal chemosensing, with special emphasis on cell surface GPCRs such as the sweet and proteinaceous taste receptors (TASRs), short- and long-chain fatty acid (FA) receptors, and bile acid receptors...
2016: F1000Research
Christian O Häusler, Michael Hanke
Here we present an annotation of locations and temporal progression depicted in the movie "Forrest Gump", as an addition to a large public functional brain imaging dataset ( The annotation provides information about the exact timing of each of the 870 shots, and the depicted location after every cut with a high, medium, and low level of abstraction. Additionally, four classes are used to distinguish the differences of the depicted time between shots. Each shot is also annotated regarding the type of location (interior/exterior) and time of day...
2016: F1000Research
Sampathkumar Rangasamy, Shannon Olfers, Brittany Gerald, Alex Hilbert, Sean Svejda, Vinodh Narayanan
Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutation in the X-linked MECP2 gene, encoding methyl-CpG-binding protein 2. We have created a mouse model ( Mecp2 A140V "knock-in" mutant) expressing the recurrent human MECP2 A140V mutation linked to an X-linked mental retardation/Rett syndrome phenotype. Morphological analyses focused on quantifying soma and nucleus size were performed on primary hippocampus and cerebellum granule neuron (CGN) cultures from mutant ( Mecp2(A140V/y)) and wild type ( Mecp2(+/y)) male mice...
2016: F1000Research
Jaime A Cardona-Ospina, Juan C Sepúlveda-Arias, L Mancilla, Luis G Gutierrez-López
Plant expression systems could be used as biofactories of heterologous proteins that have the potential to be used with biopharmaceutical aims and vaccine design. This technology is scalable, safe and cost-effective and it has been previously proposed as an option for vaccine and protein pharmaceutical development in developing countries. Here we present a proposal of how plant expression systems could be used to address Zika and chikungunya outbreaks through development of vaccines and rapid diagnostic kits...
2016: F1000Research
Israel Amirav, Mary Roduta Roberts, Huda Mussaffi, Avigdor Mandelberg, Yehudah Roth, Revital Abitbul, Anthony Luder, Hannah Blau, Soliman Alkrinawi, Micha Aviram, Marta Ben-Ami, Moshe Rotschild, Lea Bentur, David Shoseyov, Malena Cohen-Cymberknoh, Eitan Kerem, Avraham Avital, Chaim Springer, Avigdor Hevroni, Husein Dabbah, Arnon Elizur, Elie Picard, Shmuel Goldberg, Joseph Rivlin, Galit Livnat, Moran Lavie, Nael Alias, Ruth Soferman, Heike Olbrich, Johanna Raidt, Julia Wallmeier, Claudius Werner, Niki T Loges, Heymut Omran
Rationale: Primary ciliary dyskinesia (PCD) is under diagnosed and underestimated. Most clinical research has used some form of questionnaires to capture data but none has been critically evaluated particularly with respect to its end-user feasibility and utility. Objective: To critically appraise a clinical data collection questionnaire for PCD used in a large national PCD consortium in order to apply conclusions in future PCD research. Methods: We describe the development, validation and revision process of a clinical questionnaire for PCD and its evaluation during a national clinical PCD study with respect to data collection and analysis, initial completion rates and user feedback...
2016: F1000Research
David N Ku, Sarah K Ku, Beth Helfman, Nael A McCarty, Bernard J Wolff, Jonas M Winchell, Larry J Anderson
Background: Identifying lung pathogens and acute spikes in lung counts remain a challenge in the treatment of patients with cystic fibrosis (CF). Bacteria from the deep lung may be sampled from aerosols produced during coughing. Methods: A new device was used to collect and measure bacteria levels from cough aerosols of patients with CF. Sputum and oral specimens were also collected and measured for comparison. Pseudomonas aeruginosa, Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus mitis were detected in specimens using Real-Time Polymerase Chain Reaction (RT-PCR) molecular assays...
2016: F1000Research
Kateryna S Pantiukh, Nikolay N Chekanov, Igor V Zaigrin, Alexei M Zotov, Alexander M Mazur, Egor B Prokhortchouk
Concerns of traditional prenatal aneuploidy testing methods, such as low accuracy of noninvasive and health risks associated with invasive procedures, were overcome with the introduction of novel noninvasive methods based on genetics (NIPT). These were rapidly adopted into clinical practice in many countries after a series of successful trials of various independent submethods. Here we present results of own NIPT trial carried out in Moscow, Russia. 1012 samples were subjected to the method aimed at measuring chromosome coverage by massive parallel sequencing...
2016: F1000Research
M Amin Arnaout
Integrins comprise a large family of αβ heterodimeric cell adhesion receptors that are expressed on all cells except red blood cells and that play essential roles in the regulation of cell growth and function. The leukocyte integrins, which include members of the β 1, β 2, β 3, and β 7 integrin family, are critical for innate and adaptive immune responses but also can contribute to many inflammatory and autoimmune diseases when dysregulated. This review focuses on the β 2 integrins, the principal integrins expressed on leukocytes...
2016: F1000Research
Jonathan B Shurin, Michael D Burkart, Stephen P Mayfield, Val H Smith
Modern society is fueled by fossil energy produced millions of years ago by photosynthetic organisms. Cultivating contemporary photosynthetic producers to generate energy and capture carbon from the atmosphere is one potential approach to sustaining society without disrupting the climate. Algae, photosynthetic aquatic microorganisms, are the fastest growing primary producers in the world and can therefore produce more energy with less land, water, and nutrients than terrestrial plant crops. We review recent progress and challenges in developing bioenergy technology based on algae...
2016: F1000Research
Nomi L Harris, Peter J A Cock, Brad Chapman, Christopher J Fields, Karsten Hokamp, Hilmar Lapp, Monica Muñoz-Torres, Heather Wiencko
Message from the ISCB: The Bioinformatics Open Source Conference (BOSC) is a yearly meeting organized by the Open Bioinformatics Foundation (OBF), a non-profit group dedicated to promoting the practice and philosophy of Open Source software development and Open Science within the biological research community. BOSC has been run since 2000 as a two-day Special Interest Group (SIG) before the annual ISMB conference. The 17th annual BOSC ( took place in Orlando, Florida in July 2016...
2016: F1000Research
Zhonghui Guan, Judith Hellman, Mark Schumacher
Tissue injury, whether by trauma, surgical intervention, metabolic dysfunction, ischemia, or infection, evokes a complex cellular response (inflammation) that is associated with painful hyperalgesic states. Although in the acute stages it is necessary for protective reflexes and wound healing, inflammation may persist well beyond the need for tissue repair or survival. Prolonged inflammation may well represent the greatest challenge mammalian organisms face, as it can lead to chronic painful conditions, organ dysfunction, morbidity, and death...
2016: F1000Research
Robert P Fisher
How and when eukaryotic cells make the irrevocable commitment to divide remain central questions in the cell-cycle field. Parallel studies in yeast and mammalian cells seemed to suggest analogous control mechanisms operating during the G1 phase-at Start or the restriction (R) point, respectively-to integrate nutritional and developmental signals and decide between distinct cell fates: cell-cycle arrest or exit versus irreversible commitment to a round of division. Recent work has revealed molecular mechanisms underlying this decision-making process in both yeast and mammalian cells but also cast doubt on the nature and timing of cell-cycle commitment in multicellular organisms...
2016: F1000Research
Andreas Hartmann
In patients with severe, treatment-refractory Gilles de la Tourette syndrome (GTS), deep brain stimulation (DBS) of various targets has been increasingly explored over the past 15 years. The multiplicity of surgical targets is intriguing and may be partly due to the complexity of GTS, specifically the various and frequent associated psychiatric comorbidities in this disorder. Thus, the target choice may not only be aimed at reducing tics but also comorbidities. While this approach is laudable, it also carries the risk to increase confounding factors in DBS trials and patient evaluation...
2016: F1000Research
Wim E Crusio, Esha Dhawan, Elissa J Chesler, Anna Delprato
In this study we identified a quantitative trait locus (QTL) on mouse Chromosome 7 associated with locomotor activity and rearing post morphine treatment. This QTL was revealed after correcting for the effects of another QTL peak on Chromosome 10 using composite interval mapping. The positional candidate genes are Syt9 and Ppfibp2. Several other genes within the interval are linked to neural processes, locomotor activity, and the defensive response to harmful stimuli.
2016: F1000Research
Edward Gilbert-Kawai, Jonny Coppel, Hennis Phillip, Michael Grocott, Can Ince, Daniel Martin
Present knowledge of how the microcirculation is altered by prolonged exposure to hypoxia at high altitude is incomplete and modification of existing analytical techniques may improve our knowledge considerably. We set out to use a novel simplified method of measuring in vivo capillary density during an expedition to high altitude using a CytoCam incident dark field imaging video-microscope. The simplified method of data capture involved recording one-second images of the mucosal surface of the inner lip to reveal data about microvasculature density in ten individuals...
2016: F1000Research
Lilah Toker, Min Feng, Paul Pavlidis
Concern about the reproducibility and reliability of biomedical research has been rising. An understudied issue is the prevalence of sample mislabeling, one impact of which would be invalid comparisons. We studied this issue in a corpus of human transcriptomics studies by comparing the provided annotations of sex to the expression levels of sex-specific genes. We identified apparent mislabeled samples in 46% of the datasets studied, yielding a 99% confidence lower-bound estimate for all studies of 33%. In a separate analysis of a set of datasets concerning a single cohort of subjects, 2/4 had mislabeled samples, indicating laboratory mix-ups rather than data recording errors...
2016: F1000Research
Nowlan Selvapatt, Ashley Brown
Objectives: To assess the uptake of pegylated interferon (PegIFN) plus ribavirin (RBV)-based regimens in patients with hepatitis C virus (HCV) in a large, single-centre, real-world setting over 10 years. Methods: This was a single centre, retrospective analysis of data from patients who attended their first appointment for treatment of HCV genotype 1-3 between 2003 and 2013. Patients were stratified by HCV genotype. The total number of patients who attended their first appointment, incidence of patients who did not proceed to treatment and associated reasons, and incidence of patients treated were analysed...
2016: F1000Research
Rainer Engelken, Farzad Farkhooi, David Hansel, Carl van Vreeswijk, Fred Wolf
Neuronal activity in the central nervous system varies strongly in time and across neuronal populations. It is a longstanding proposal that such fluctuations generically arise from chaotic network dynamics. Various theoretical studies predict that the rich dynamics of rate models operating in the chaotic regime can subserve circuit computation and learning. Neurons in the brain, however, communicate via spikes and it is a theoretical challenge to obtain similar rate fluctuations in networks of spiking neuron models...
2016: F1000Research
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