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https://www.readbyqxmd.com/read/29352755/a-mos1-transposase-in-vivo-assay-to-screen-new-hiv-1-integrase-inhibitors
#1
Mariana Cancian, Elgion L S Loreto
The integrase and transposase enzymes of retrovirus and transposons, respectively, share the catalytic DDE domain. In vitro assays showed that inhibitors of HIV-1 integrase generally inhibit the mariner Mos1 transposase. Using a Drosophila strain in which the mobilisation of the mariner element can be quantified by mosaic eyes, we showed that flies maintained in medium containing 210 µM to 4 mM of raltegravir, or 1 or 2 mM of dolutegravir, which are HIV-1 integrase inhibitor used in AIDS treatment, have 23-33% less somatic mobilisation in mosaic eyes when treated with raltegravir and 28-32% when treated with dolutegravir...
January 19, 2018: Genetica
https://www.readbyqxmd.com/read/29352747/clathrin-and-ap1-are-required-for-apical-sorting-of-gpi-aps-in-biosynthetic-and-recycling-routes-in-mdck-cells
#2
Guillaume Alain Castillon, Patricia Burriat-Couleru, Daniel Abegg, Nina Criado Santos, Reika Watanabe
Recently studies in animal models demonstrate potential roles for clathrin and AP1 in apical protein sorting in epithelial tissue. However, the precise functions of these proteins in apical protein transport remain unclear. Here, we reveal mis-targeting of endogenous GPI-APs and soluble secretory proteins in MDCK cells upon clathrin heavy chain or AP1 subunit knockdown (KD). Using a novel directional endocytosis and recycling assay, we found that these KD cells are not only affected for apical sorting of GPI-APs in biosynthetic pathway but also for their apical recycling and basal to apical transcytosis routes...
January 20, 2018: Traffic
https://www.readbyqxmd.com/read/29352739/determination-of-protein-oligomeric-structure-from-small-angle-x-ray-scattering
#3
REVIEW
David A Korasick, John J Tanner
Small-angle X-ray scattering (SAXS) is useful for determining the oligomeric states and quaternary structures of proteins in solution. The average molecular mass in solution can be calculated directly from a single SAXS curve collected on an arbitrary scale from a sample of unknown protein concentration, without the need for beamline calibration or protein standards. The quaternary structure in solution can be deduced by comparing the experimental SAXS curve to theoretical curves calculated from proposed models of the oligomer...
January 20, 2018: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/29352735/s-nitrosated-poly-propylene-sulfide-nanoparticles-for-enhanced-nitric-oxide-delivery-to-lymphatic-tissues
#4
Alex Schudel, Lauren F Sestito, Susan N Thomas
Nitric oxide (NO) is a therapeutic implicated for the treatment of diseases affecting lymphatic tissues, which range from infectious and cardiovascular diseases to cancer. Existing technologies available for NO therapy, however, provide poor bioactivity within lymphatic tissues. In this work, we address this technology gap with a NO encapsulation and delivery strategy leveraging the formation of S-nitrosothiols on lymphatic-targeting Pluronic-stabilized, poly(propylene sulfide)-core nanoparticles (SNO-NP). We evaluated in vivo the lymphatic versus systemic delivery of NO resulting from intradermal administration of SNO-NP benchmarked against a commonly used, commercially available small molecule S-nitrosothiol NO donor, examined signs of toxicity systemically as well as localized to the site of injection, and investigated SNO effects on lymphatic transport and NP uptake by LN-resident cells...
January 20, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29352734/resistance-to-tyrosine-kinase-inhibitors-in-non-small-cell-lung-cancer-the-role-of-cancer-stem-cells
#5
REVIEW
Marzia Del Re, Elena Arrigoni, Giuliana Restante, Antonio Passaro, Eleonora Rofi, Stefania Crucitta, Filippo De Marinis, Antonello Di Paolo, Romano Danesi
Among the potential mechanisms involved in resistance to tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC), the manifestation of stem-like properties in cancer cells seems to have a crucial role. Alterations involved in the development of TKI resistance may be acquired in a very early phase of tumorigenesis, supporting the hypothesis that these aberrations may be present in cancer stem cells (CSCs). In this regard, the characterization of tumor subclones in the initial phase and the identification of the CSCs may be helpful in planning a specific treatment to target selected biomarkers, suppress tumor growth, and prevent drug resistance...
January 20, 2018: Stem Cells
https://www.readbyqxmd.com/read/29352727/re-evaluation-of-target-lipid-model-derived-hc5-predictions-for-hydrocarbons
#6
Joy A McGrath, Christopher J Fanelli, Dominic M Di Toro, Thomas F Parkerton, Aaron D Redman, Miriam Leon Paumen, Mike Comber, Charles V Eadsforth, Klaas den Haan
The Target Lipid Model (TLM) has been previously applied to predict the aquatic toxicity of hydrocarbons and other non-ionic organic chemicals and for deriving HC5 values, concentrations above which 95% of species should be protected. Several concerns were identified with the TLM-derived HC5 when applied in a substance risk assessment context. These shortcomings were addressed by expanding the acute and chronic toxicity databases to include more diverse taxonomic groups and increase the number of species. The TLM was recalibrated with these expanded databases resulting in critical target lipid body burdens and acute-to-chronic ratios that met the required guidelines for using species sensitivity distributions in substance risk assessment...
January 20, 2018: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/29352717/should-we-use-cell-of-origin-and-dual-protein-expression-in-treating-dlbcl
#7
REVIEW
Peter A Riedell, Sonali M Smith
Treatment outcomes in diffuse large B-cell lymphoma (DLBCL) following standard R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) therapy is highly variable and dependent on a number of clinical, biologic, and genetic features. The identification of molecular heterogeneity via gene expression profiling dichotomizes patients based on the cell of origin (COO) model into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) subsets, with ABC-DLBCL having a worse outcome...
December 24, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/29352708/a-systematic-review-and-discussion-of-symptom-specific-cognitive-behavioural-approaches-to-delusions-and-hallucinations
#8
Tania M Lincoln, Emmanuelle Peters
Studies on cognitive behavioural therapy for psychosis (CBTp) have developed from evaluating generic approaches to focusing on specific symptoms. The evidence for targeted studies on delusions and hallucinations was reviewed. We included randomized controlled trials (RCTs) examining the effect of individualized CBT-based interventions focusing either on delusions or on hallucinations. Twelve suitable RCTs were identified. Four RCTs focused on delusions, of which three took a focused approach targeting mechanisms assumed causal to persecutory delusions...
January 16, 2018: Schizophrenia Research
https://www.readbyqxmd.com/read/29352706/environmental-conditions-in-health-care-facilities-in-low-and-middle-income-countries-coverage-and-inequalities
#9
Ryan Cronk, Jamie Bartram
Safe environmental conditions and the availability of standard precaution items are important to prevent and treat infection in health care facilities (HCFs) and to achieve Sustainable Development Goal (SDG) targets for health and water, sanitation, and hygiene. Baseline coverage estimates for HCFs have yet to be formed for the SDGs; and there is little evidence describing inequalities in coverage. To address this, we produced the first coverage estimates of environmental conditions and standard precaution items in HCFs in low- and middle-income countries (LMICs); and explored factors associated with low coverage...
January 11, 2018: International Journal of Hygiene and Environmental Health
https://www.readbyqxmd.com/read/29352669/tms-of-primary-motor-cortex-with-a-biphasic-pulse-activates-two-independent-sets-of-excitable-neurones
#10
Martin Sommer, Matteo Ciocca, Raffaella Chieffo, Paul Hammond, Andreas Neef, Walter Paulus, John C Rothwell, Ricci Hannah
BACKGROUND: Biphasic pulses produced by most commercially available TMS machines have a cosine waveform, which makes it difficult to study the interaction between the two phases of stimulation. OBJECTIVE: We used a controllable pulse TMS (cTMS) device delivering quasi-rectangular pulse outputs to investigate whether monophasic are more effective than biphasic pulses. METHODS: Temporally symmetric ("biphasic") or highly asymmetric ("monophasic") charge-balanced biphasic stimuli were used to target the hand area of motor cortex in the anterior-posterior (AP) or posterior-anterior (PA) initial current direction...
January 5, 2018: Brain Stimulation
https://www.readbyqxmd.com/read/29352668/the-effect-of-single-and-repeated-prefrontal-intermittent-theta-burst-stimulation-on-cortical-reactivity-and-working-memory
#11
Sung Wook Chung, Nigel C Rogasch, Kate E Hoy, Paul B Fitzgerald
BACKGROUND: With an increasing interest in the use of theta burst stimulation (TBS) as a cognitive enhancer and a potential therapeutic tool for psychiatric disorders, there is a need to identify optimal parameters of TBS in the prefrontal cortex. OBJECTIVE/HYPOTHESIS: This study examined the effect of two blocks of prefrontal intermittent TBS (iTBS) on cortical reactivity and working memory performance, compared to one block of iTBS and sham stimulation. We hypothesized that greater cortical effects would be obtained with two blocks of iTBS...
January 8, 2018: Brain Stimulation
https://www.readbyqxmd.com/read/29352629/an-in-silico-comparative-dosimetric-study-of-postmastectomy-locoregional-irradiation-using-intensity-modulated-vs-3-dimensional-conventional-radiotherapy
#12
Pooja Khullar, Charu Garg, Sujit Nath Sinha, Inderjit Kaur, Niloy Ranjan Datta
An in silico dosimetric evaluation of intensity-modulated radiation therapy (IMRT) vs 3-dimensional conventional radiation therapy (3D-CRT) treatment plans in postmastectomy radiation therapy (PMRT) to the chest wall and regional lymphatics was conducted. Twenty-five consecutive patients with breast cancer referred for locoregional PMRT, stages T2-4 with N1-3, were planned to receive 50 Gy in 25 fractions with IMRT. Additionally, a 3D-CRT plan was generated using identical contours for the clinical target volumes (CTV), planning target volumes (PTV), and organs at risk (OAR)...
January 15, 2018: Medical Dosimetry: Official Journal of the American Association of Medical Dosimetrists
https://www.readbyqxmd.com/read/29352609/induction-of-mitophagy-in-the-hei-oc1-auditory-cell-line-and-activation-of-the-atg12-lc3-pathway-in-the-organ-of-corti
#13
Cristian Setz, Anne-Sophie Benischke, Anna Catharina Pinho Ferreira Bento, Yves Brand, Soledad Levano, Franziska Paech, Katharina Leitmeyer, Daniel Bodmer
Autophagy is a highly evolutionary conserved quality control defense mechanism within cells, which has also been implicated in cell death processes. In the mammalian inner ear, autophagy has been shown to play a role during early morphogenesis as well as in adult cochlear hair cells exposed to ototoxic insults. Mitophagy, a selective autophagic cell process targeting mitochondria, hasn't been studied in the inner ear so far. On this work, we searched for molecular indicators of mitophagy within House Ear Institute-Organ of Corti-1 (HEI-OC1) cells as well as in the organ of Corti (OC)...
January 11, 2018: Hearing Research
https://www.readbyqxmd.com/read/29352607/integrated-lung-tissue-mechanics-one-piece-at-a-time-computational-modeling-across-the-scales-of-biology
#14
REVIEW
Kelly S Burrowes, Amin Iravani, Wendy Kang
The lung is a delicately balanced and highly integrated mechanical system. Lung tissue is continuously exposed to the environment via the air we breathe, making it susceptible to damage. As a consequence, respiratory diseases present a huge burden on society and their prevalence continues to rise. Emergent function is produced not only by the sum of the function of its individual components but also by the complex feedback and interactions occurring across the biological scales - from genes to proteins, cells, tissue and whole organ - and back again...
January 12, 2018: Clinical Biomechanics
https://www.readbyqxmd.com/read/29352599/-detection-of-chlamydia-abortus-in-bovine-reproductive-losses-in-the-province-of-la-pampa-argentina
#15
María Del C Rojas, Marcelo Fort, Simone Bettermann, Carolina Entrocassi, Sixto R Costamagna, Konrad Sachse, Marcelo Rodríguez Fermepin
Reproductive losses linked to an infectious etiology in bovine cattle are a major economic concern worldwide. In Argentina, more than 50% of abortion cases have unknown causes. Species belonging to Chlamydiaceae family are frequent etiologic agents of abortion around the world; however, there is yet no information on their prevalence in Argentina. The objective of this work was to identify Chlamydia spp., and particularly C. abortus in reproductive losses from bovine cattle in La Pampa, Argentina. Real time PCR targeting Chlamydiaceae-specific DNA fragments was performed on 251 samples obtained from bovine abortions and stillborns, and ArrayTube was used for species identification on positive samples...
January 16, 2018: Revista Argentina de Microbiología
https://www.readbyqxmd.com/read/29352597/potential-drug-targets-in-the-mycobacterium-tuberculosis-cytochrome-p450-system
#16
REVIEW
Paul R Ortiz de Montellano
The Mycobacterium tuberculosis genome encodes twenty cytochrome P450 enzymes, most or all of which appear to have specific physiological functions rather than being devoted to the removal of xenobiotics. However, in many cases their specific functions remain obscure. Considerable spectroscopic, biophysical, crystallographic, and catalytic information is available on nine of these cytochrome P450 enzymes, although gaps exist in our knowledge of even these enzymes. The available evidence indicates that at least three of the better-characterized enzymes are promising targets for antituberculosis drug discovery...
January 12, 2018: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/29352570/the-nlrp3-inflammasome-and-the-emerging-role-of-colchicine-to-inhibit-atherosclerosis-associated-inflammation
#17
REVIEW
Gonzalo J Martínez, David S Celermajer, Sanjay Patel
Atherosclerosis is considered a chronic inflammatory disease of the arterial wall. Recently, compelling evidence has arisen for the role of monocytes and neutrophils and a particular protein complex that resides within these cells - the NLRP3 inflammasome - in atherosclerosis-associated inflammation. It is now also known that cholesterol crystals are present through all stages of atherosclerosis and can activate the NLRP3 inflammasome within these inflammatory cells to produce interleukin 1β and interleukin 18 - key mediators in the inflammatory cascade that drive plaque progression and instability...
December 25, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29352551/prevention-of-child-maltreatment-strategic-targeting-of-a-curvilinear-relationship-between-adversity-and-psychiatric-impairment
#18
John N Constantino
No abstract text is available yet for this article.
February 2018: World Psychiatry: Official Journal of the World Psychiatric Association (WPA)
https://www.readbyqxmd.com/read/29352548/prediction-of-psychosis-across-protocols-and-risk-cohorts-using-automated-language-analysis
#19
Cheryl M Corcoran, Facundo Carrillo, Diego Fernández-Slezak, Gillinder Bedi, Casimir Klim, Daniel C Javitt, Carrie E Bearden, Guillermo A Cecchi
Language and speech are the primary source of data for psychiatrists to diagnose and treat mental disorders. In psychosis, the very structure of language can be disturbed, including semantic coherence (e.g., derailment and tangentiality) and syntactic complexity (e.g., concreteness). Subtle disturbances in language are evident in schizophrenia even prior to first psychosis onset, during prodromal stages. Using computer-based natural language processing analyses, we previously showed that, among English-speaking clinical (e...
February 2018: World Psychiatry: Official Journal of the World Psychiatric Association (WPA)
https://www.readbyqxmd.com/read/29352539/income-inequality-and-depression-a-systematic-review-and-meta-analysis-of-the-association-and-a-scoping-review-of-mechanisms
#20
Vikram Patel, Jonathan K Burns, Monisha Dhingra, Leslie Tarver, Brandon A Kohrt, Crick Lund
Most countries have witnessed a dramatic increase of income inequality in the past three decades. This paper addresses the question of whether income inequality is associated with the population prevalence of depression and, if so, the potential mechanisms and pathways which may explain this association. Our systematic review included 26 studies, mostly from high-income countries. Nearly two-thirds of all studies and five out of six longitudinal studies reported a statistically significant positive relationship between income inequality and risk of depression; only one study reported a statistically significant negative relationship...
February 2018: World Psychiatry: Official Journal of the World Psychiatric Association (WPA)
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