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https://www.readbyqxmd.com/read/28213391/the-politics-and-policies-of-regulating-generics-in-latin-america-a-survey-of-seventeen-states
#1
Cassandra M Sweet
When patents expire, are equivalent generic alternatives available to citizens? This article contributes to current discussion on access to medicine in the aftermath of the World Trade Organization's Agreement on Trade-Related Aspects of Intellectual Property Rights (TRIPS). The focus is on off-patent or "generic" medicines: their product definitions, quality standards and prescription procedures. Drawing from a survey conducted of seventeen countries across the Latin American region, this article examines the differences in definition of off-patent products and the paradox of their relatively lower consumption across multiple developing states...
February 17, 2017: Journal of Health Politics, Policy and Law
https://www.readbyqxmd.com/read/28213002/a-phase-ii-trial-of-dovitinib-in-previously-treated-advanced-pleural-mesothelioma-the-ontario-clinical-oncology-group
#2
Scott A Laurie, Desiree Hao, Natasha B Leighl, John Goffin, Abderrahim Khomani, Ashish Gupta, Christina L Addison, Anita Bane, Jean Seely, Marc L Filion, Gregory R Pond, Mark N Levine
OBJECTIVES: Following failure of a platinum-antifolate combination regimen, there is no standard therapy for advanced malignant pleural mesothelioma (MPM). The fibroblast growth factor receptor (FGFR) signaling pathways may be a relevant target in MPM. Dovitinib inhibits multiple tyrosine receptor kinases, predominantly the vascular endothelial growth factor receptors (VEGFR), but also FGFRs, and could be active in MPM. METHODS: This open-label multicentre phase II trial [NCT01769547] enrolled fit, consenting adult patients with advanced MPM who had previously received platinum-antifolate combination chemotherapy and up to one additional line of systemic therapy...
February 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28212815/systematic-testing-of-enzyme-perturbation-sensitivities-via-graded-dcas9-modulation-in-saccharomyces-cerevisiae
#3
Matthew Deaner, Hal S Alper
Dissecting genotype-phenotype relationships in a high-throughput and scalable manner is still an unresolved problem facing metabolic engineers. While the RNA-guided nuclease Cas9 has been repurposed as a programmable transcription regulator, its application has typically been limited to binary on/off regulation and thus misses informative and potentially optimal intermediate levels of gene expression. In this work, we establish a rapid method for fine-tuned, graded expression of pathway enzymes via dCas9 regulation by varying sgRNA target location as the dominant parameter...
February 14, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28199309/phosphatidylinositol-3-kinase-%C3%AE-blockade-increases-genomic-instability-in-b-cells
#4
Mara Compagno, Qi Wang, Chiara Pighi, Taek-Chin Cheong, Fei-Long Meng, Teresa Poggio, Leng-Siew Yeap, Elif Karaca, Rafael B Blasco, Fernanda Langellotto, Chiara Ambrogio, Claudia Voena, Adrian Wiestner, Siddha N Kasar, Jennifer R Brown, Jing Sun, Catherine J Wu, Monica Gostissa, Frederick W Alt, Roberto Chiarle
Activation-induced cytidine deaminase (AID) is a B-cell-specific enzyme that targets immunoglobulin genes to initiate class switch recombination and somatic hypermutation. In addition, through off-target activity, AID has a much broader effect on genomic instability by initiating oncogenic chromosomal translocations and mutations involved in the development and progression of lymphoma. AID expression is tightly regulated in B cells and its overexpression leads to enhanced genomic instability and lymphoma formation...
February 15, 2017: Nature
https://www.readbyqxmd.com/read/28197921/sumoylation-in-craniofacial-disorders
#5
Erwin Pauws, Philip Stanier
Craniofacial development requires a complex series of coordinated and finely tuned events to take place, during a relatively short time frame. These events are set in motion by switching on and off transcriptional cascades that involve the use of numerous signalling pathways and a multitude of factors that act at the site of gene transcription. It is now well known that amidst the subtlety of this process lies the intricate world of protein modification, and the posttranslational addition of the small ubiquitin -like modifier, SUMO, is an example that has been implicated in this process...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28193818/processing-of-single-photon-responses-in-the-mammalian-on-and-off-retinal-pathways-at-the-sensitivity-limit-of-vision
#6
Daisuke Takeshita, Lina Smeds, Petri Ala-Laurila
Visually guided behaviour at its sensitivity limit relies on single-photon responses originating in a small number of rod photoreceptors. For decades, researchers have debated the neural mechanisms and noise sources that underlie this striking sensitivity. To address this question, we need to understand the constraints arising from the retinal output signals provided by distinct retinal ganglion cell types. It has recently been shown in the primate retina that On and Off parasol ganglion cells, the cell types likely to underlie light detection at the absolute visual threshold, differ fundamentally not only in response polarity, but also in the way they handle single-photon responses originating in rods...
April 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28191938/constrained-multistate-sequence-design-for-nucleic-acid-reaction-pathway-engineering
#7
Brian R Wolfe, Nicholas J Porubsky, Joseph N Zadeh, Robert M Dirks, Niles A Pierce
We describe a framework for designing the sequences of multiple nucleic acid strands intended to hybridize in solution via a prescribed reaction pathway. Sequence design is formulated as a multistate optimization problem using a set of target test tubes to represent reactant, intermediate, and product states of the system, as well as to model crosstalk between components. Each target test tube contains a set of desired "on-target" complexes, each with a target secondary structure and target concentration, and a set of undesired "off-target" complexes, each with vanishing target concentration...
February 13, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28187707/transcriptome-analysis-of-coding-and-long-non-coding-rnas-highlights-the-regulatory-network-of-cascade-initiation-of-permanent-molars-in-miniature-pigs
#8
Fu Wang, Yang Li, Xiaoshan Wu, Min Yang, Wei Cong, Zhipeng Fan, Jinsong Wang, Chunmei Zhang, Jie Du, Songlin Wang
BACKGROUND: In diphyodont mammals, the additional molars (permanent molars) bud off from the posterior-free end of the primary dental lamina compared with successional teeth (replacement teeth) budding off from the secondary dental lamina. The diphyodont miniature pig has proved to be a valuable model for studying human molar morphogenesis. The additional molars show a sequential initiation pattern related to the specific tooth development stage of additional molars in miniature pigs during the morphogenesis of additional molars...
February 10, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28183259/targeting-melatonin-mt2-receptors-a-novel-pharmacological-avenue-for-inflammatory-and-neuropathic-pain
#9
Luca Posa, Danilo De Gregorio, Gabriella Gobbi, Stefano Comai
Melatonin (MLT) has been implicated in several pathophysiological states, including pain. MLT mostly activates two G-protein coupled receptors, MT1 and MT2. In this review, we present the analgesic properties of MLT in preclinical and clinical studies, giving particular emphasis to the effects mediated by MT2 receptors and to recent investigations demonstrating the analgesic effects of MT2 receptor partial agonists in chronic and acute/inflammatory pain conditions. MT2 receptors are localized in specific brain areas, including the reticular and the ventromedial nuclei of the thalamus (part of the ascending nociceptive pathway) and the ventrolateral periaqueductal grey matter (vlPAG) (part of the descending antinociceptive pathway)...
February 8, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28179977/programmable-genome-editing-tools-and-their-regulation-for-efficient-genome-engineering
#10
REVIEW
Tuhin Kumar Guha, Alvan Wai, Georg Hausner
Targeted genome editing has become a powerful genetic tool for studying gene function or for modifying genomes by correcting defective genes or introducing genes. A variety of reagents have been developed in recent years that can generate targeted double-stranded DNA cuts which can be repaired by the error-prone, non-homologous end joining repair system or via the homologous recombination-based double-strand break repair pathway provided a suitable template is available. These genome editing reagents require components for recognizing a specific DNA target site and for DNA-cleavage that generates the double-stranded break...
2017: Computational and Structural Biotechnology Journal
https://www.readbyqxmd.com/read/28177220/mechanistic-investigation-into-the-effect-of-sulfuration-on-the-few-catalysts-for-the-selective-catalytic-reduction-of-nox-with-nh3
#11
Hui Wang, Zhenping Qu, Shicheng Dong, Chen Tang
Iron tungsten (FeW) catalyst is a potential candidate for the selective catalytic reduction (SCR) of NOx with ammonia because of its excellent performance in a wide operating window. Sulfur poisoning effects in SCR catalysts have long been recognized as a challenge in development of efficient catalysts for applications. In this paper, the impact of sulfuration on catalyst structure, NH3-SCR reaction performance and mechanism was systematically investigated through spectroscopic and temperature-programmed approaches...
February 16, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28166907/practice-makes-perfect-performance-optimisation-in-arboreal-parkour-athletes-illuminates-the-evolutionary-ecology-of-great-ape-anatomy
#12
Lewis G Halsey, Samuel R L Coward, Robin H Crompton, Susannah K S Thorpe
An animal's size is central to its ecology, yet remarkably little is known about the selective pressures that drive this trait. A particularly compelling example is how ancestral apes evolved large body mass in such a physically and energetically challenging environment as the forest canopy, where weight-bearing branches and lianas are flexible, irregular and discontinuous, and the majority of preferred foods are situated on the most flexible branches at the periphery of tree crowns. To date the issue has been intractable due to a lack of relevant fossil material, the limited capacity of the fossil record to reconstruct an animal's behavioural ecology and the inability to measure energy consumption in freely moving apes...
February 2017: Journal of Human Evolution
https://www.readbyqxmd.com/read/28164334/ethylene-response-factor-74-erf74-plays-an-essential-role-in-controlling-a-respiratory-burst-oxidase-homolog-d-rbohd-dependent-mechanism-in-response-to-different-stresses-in-arabidopsis
#13
Yuan Yao, Run Jun He, Qiao Li Xie, Xian Hai Zhao, Xiao Mei Deng, Jun Bo He, Lili Song, Jun He, Alan Marchant, Xiao-Yang Chen, Ai-Min Wu
Recent studies indicate that the ETHYLENE RESPONSE FACTOR VII (ERF-VII) transcription factor is an important regulator of osmotic and hypoxic stress responses in plants. However, the molecular mechanism of ERF-VII-mediated transcriptional regulation remains unclear. Here, we investigated the role of ERF74 (a member of the ERF-VII protein family) by examining the abiotic stress tolerance of an ERF74 overexpression line and a T-DNA insertion mutant using flow cytometry, transactivation and electrophoretic mobility shift assays...
March 2017: New Phytologist
https://www.readbyqxmd.com/read/28163785/efficient-estimation-of-the-maximum-metabolic-productivity-of-batch-systems
#14
Peter C St John, Michael F Crowley, Yannick J Bomble
BACKGROUND: Production of chemicals from engineered organisms in a batch culture involves an inherent trade-off between productivity, yield, and titer. Existing strategies for strain design typically focus on designing mutations that achieve the highest yield possible while maintaining growth viability. While these methods are computationally tractable, an optimum productivity could be achieved by a dynamic strategy in which the intracellular division of resources is permitted to change with time...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/28163187/loss-of-ssq1-leads-to-mitochondrial-dysfunction-activation-of-autophagy-and-cell-cycle-arrest-due-to-iron-overload-triggered-by-mitochondrial-iron-sulfur-cluster-assembly-defects-in-candida-albicans
#15
Yijie Dong, Dan Zhang, Qilin Yu, Qiang Zhao, Chenpeng Xiao, Kai Zhang, Chang Jia, Sijia Chen, Bing Zhang, Biao Zhang, Mingchun Li
Iron-sulfur clusters perform essential functions in enzymatic catalysis and homeostatic regulation. Here we for the first time identified Ssq1 as an essential component for iron-sulfur cluster assembly in Candida albicans. Ssq1 played an important role in cell growth. Shutting off SSQ1 led to accumulation of intracellular iron, especially in mitochondria, and disorder of intracellular iron regulation. In tetO-SSQ1, iron overloading triggered the oxidative damage of mitochondrial function. Surprisingly, disruption of SSQ1 activated autophagic pathway...
February 3, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28163069/adipose-derived-stem-cells-protect-skin-flaps-against-ischemia-reperfusion-injury-via-interleukin-6-expression
#16
Chi-Ming Pu, Chen-Wei Liu, Chan-Jung Liang, Yu-Hsiu Yen, Shun-Hua Chen, Ya-Fen Jiang-Shieh, Chung-Liang Chien, Ya-Chun Chen, Yuh-Lien Chen
Flap necrosis is the most frequent postoperative complication encountered in reconstructive surgery. We elucidated whether adipose-derived stem cells (ADSCs) and their derivatives might induce neovascularization and protect skin flaps during ischemia/reperfusion (I/R) injury. Flaps were subjected to 3 h of ischemia by ligating long thoracic vessels and then to blood reperfusion. Q-tracker-labeled ADSCs, conditioned media (ADSC-CM), or exosomes (ADSC-Exo) were injected into the flaps. These treatments led to significantly increase flap survival and capillary density compared to I/R on postoperative day 5...
February 2, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28161988/therapeutic-inhibition-of-bcl-2-and-related-family-members
#17
Michelle Levy, David Claxton
BCL-2 proteins are key players in the balance of cell life and death. Their roles in the development and biology of cancer have been well established and continue to be investigated. Understanding the mechanisms by which these proteins regulate apoptosis has led to the development of small molecule targeted therapies that act to overcome the cell's ability to evade programmed cell death. Areas covered: The biology of the intrinsic apoptotic pathway is reviewed with attention to the varied roles of the anti-apoptotic members of the BCL-2 family...
February 6, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28161085/erratum-to-off-target-effect-of-sildenafil-on-postsurgical-erectile-dysfunction-alternate-pathways-and-localized-delivery-system
#18
(no author information available yet)
No abstract text is available yet for this article.
February 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/28161040/heavy-pollution-episodes-transport-pathways-and-potential-sources-of-pm2-5-during-the-winter-of-2013-in-chengdu-china
#19
Tingting Liao, Shan Wang, Jie Ai, Ke Gui, Bolong Duan, Qi Zhao, Xiao Zhang, Wanting Jiang, Yang Sun
Air mass concentration data from 8 environmental quality monitoring sites and meteorological data of Chengdu from 1 December 2013 to 28 February 2014 were used in this study. Chengdu suffered five continuous heavy pollutions during this winter due to the basin terrain and the meteorological conditions of low wind speed, low precipitation and high relative humidity. Analysing the hourly resolution time series of pollutants' concentrations, variation of PM2.5 in the urban area followed a growing "saw-tooth cycle" pattern during the heavy pollution, with a daily cycle of bimodal distribution...
February 1, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28160235/characteristics-of-patients-with-an-unplanned-admission-to-an-acute-palliative-care-unit
#20
Sebastiano Mercadante, Claudio Adile, Patrizia Ferrera, Alessandra Casuccio
The aim of this cohort study is to compare the symptom burden of patients who have an unplanned admission to an acute palliative care unit (APCU) with patients who have a regular planned admission. A consecutive sample of advanced cancer patients who were admitted to an APCU was prospectively assessed. The reasons and the kind of admission were recorded (unplanned, UP, or planned, P). Anticancer treatments, whether patients were on/off treatment or uncertain, previous care setting, and who referred the patient to the unit were also recorded...
February 3, 2017: Internal and Emergency Medicine
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