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https://www.readbyqxmd.com/read/28640808/transmembrane-helical-interactions-in-the-cftr-channel-pore
#1
Jhuma Das, Andrei A Aleksandrov, Liying Cui, Lihua He, John R Riordan, Nikolay V Dokholyan
Mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene affect CFTR protein biogenesis or its function as a chloride channel, resulting in dysregulation of epithelial fluid transport in the lung, pancreas and other organs in cystic fibrosis (CF). Development of pharmaceutical strategies to treat CF requires understanding of the mechanisms underlying channel function. However, incomplete 3D structural information on the unique ABC ion channel, CFTR, hinders elucidation of its functional mechanism and correction of cystic fibrosis causing mutants...
June 22, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28640668/absence-of-the-fragile-x-mental-retardation-protein-results-in-defects-of-rna-editing-of-neuronal-mrnas-in-mouse
#2
Alice Filippini, Daniela Bonini, Caroline Lacoux, Laura Pacini, Maria Zingariello, Laura Sancillo, Daniela Bosisio, Valentina Salvi, Jessica Mingardi, Luca La Via, Francesca Zalfa, Claudia Bagni, Alessandro Barbon
The fragile X syndrome (FXS), the most common form of inherited intellectual disability, is due to the absence of FMRP, a protein regulating RNA metabolism. Recently, an unexpected function of FMRP in modulating the activity of Adenosine Deaminase Acting on RNA (ADAR) enzymes has been reported both in Drosophila and Zebrafish. ADARs are RNA-binding proteins that increase transcriptional complexity through a post-transcriptional mechanism called RNA editing. In order to evaluate the ADAR2-FMRP interaction in mammals we analysed several RNA editing re-coding sites in the fmr1 knockout (KO) mice...
June 22, 2017: RNA Biology
https://www.readbyqxmd.com/read/28636915/probing-the-structural-dynamics-of-the-nmda-receptor-activation-by-coarse-grained-modeling
#3
Wenjun Zheng, Han Wen, Gary J Iacobucci, Gabriela K Popescu
N-Methyl-D-aspartate (NMDA) receptors are glutamate-gated excitatory channels that play essential roles in brain functions. High-resolution structures have been solved for an allosterically inhibited and agonist-bound form of a functional NMDA receptor; however, other key functional states (particularly the active open-channel state) were only resolved at moderate resolutions by cryo-electron microscopy (cryo-EM). To decrypt the mechanism of the NMDA receptor activation, structural modeling is essential to provide presently missing information about structural dynamics...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28636906/flexible-fitting-of-atomic-models-into-cryo-em-density-maps-guided-by-helix-correspondences
#4
Hang Dou, Derek W Burrows, Matthew L Baker, Tao Ju
Although electron cryo-microscopy (cryo-EM) has recently achieved resolutions of better than 3 Å, at which point molecular modeling can be done directly from the density map, analysis and annotation of a cryo-EM density map still primarily rely on fitting atomic or homology models to the density map. In this article, we present, to our knowledge, a new method for flexible fitting of known or modeled protein structures into cryo-EM density maps. Unlike existing methods that are guided by local density gradients, our method is guided by correspondences between the α-helices in the density map and model, and does not require an initial rigid-body fitting step...
June 20, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/28636123/sem-imaging-of-the-stimulatory-response-of-raw264-7-cells-against-porphyromonas-gingivalis-using-a-simple-technique-employing-new-conductive-materials
#5
Chisato Takahashi, Yoshiki Umemura, Ayako Naka, Hiromitsu Yamamoto
In the medical biology, it is essential to understand not only biological morphology but also the interaction between biological materials and agents. To study these, electron microscopy (EM) is often utilized. However, sample preparation techniques for EM require a high level of skill and a considerable time. Here, we conducted EM using a simple technique employing a conductive liquid, BEL-1, and compared the results with another simple technique employing an ionic liquid, 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4 ])...
June 21, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
https://www.readbyqxmd.com/read/28635275/infrared-determination-of-the-protonation-state-of-a-key-histidine-residue-in-the-photosynthetic-water-oxidizing-center
#6
Shin Nakamura, Takumi Noguchi
Photosynthetic water oxidation is performed at the Mn4CaO5 cluster in photosystem II (PSII). The protonation structures of amino acid residues and water molecules around the Mn4CaO5 cluster are crucial in water oxidation reactions. In this study, we determined the protonation state of a key His residue in water oxidation, D1-H337, which is directly hydrogen bonded with the oxygen atom of the Mn4CaO5 cluster, using polarized attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy. Flash-induced polarized ATR-FTIR difference spectra upon the S1→S2 transition of oriented PSII membranes showed broad negative and positive features around 2600 and 2900 cm-1, respectively, with large dichroic ratios, accompanied with several minor peaks attributable to the Fermi resonance of a His NH vibration...
June 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28634165/diabetes-em-movimento-a-portuguese-web-based-platform-to-support-exercise-prescription-by-medical-doctors
#7
Romeu Mendes, Nelson Sousa, Marcos Agostinho, Victor Machado Reis, José Luís Themudo-Barata
No abstract text is available yet for this article.
June 20, 2017: British Journal of Sports Medicine
https://www.readbyqxmd.com/read/28632306/analytical-modeling-provides-new-insight-into-complex-mutual-coupling-between-surface-loops-at-ultrahigh-fields
#8
N I Avdievich, A Pfrommer, I A Giapitzakis, A Henning
Ultrahigh-field (UHF) (≥7 T) transmit (Tx) human head surface loop phased arrays improve both the Tx efficiency (B1(+) /√P) and homogeneity in comparison with single-channel quadrature Tx volume coils. For multi-channel arrays, decoupling becomes one of the major problems during the design process. Further insight into the coupling between array elements and its dependence on various factors can facilitate array development. The evaluation of the entire impedance matrix Z for an array loaded with a realistic voxel model or phantom is a time-consuming procedure when performed using electromagnetic (EM) solvers...
June 20, 2017: NMR in Biomedicine
https://www.readbyqxmd.com/read/28632272/interfacial-synthesis-of-a-three-dimensional-hierarchical-mos2-ns-ag-np-nanocomposite-as-a-sers-nanosensor-for-ultrasensitive-thiram-detection
#9
Xiu Liang, Yi-Shuo Wang, Ting-Ting You, Xiao-Juan Zhang, Nan Yang, Guang-Sheng Wang, Peng-Gang Yin
Interfacial self-assembly of ordered nanostructures at oil-water interfaces towards the fabrication of nanofilms has attracted the interest of plenty of scientists, since its discovery in 2004. Herein, further developments have been achieved, and we report a new strategy for the synthesis of a three-dimensional (3D) hierarchical nanostructure, through an interfacial synthesis driven microemulsion process. Thus, the synthesis route has been simplified, with the rigorous experimental conditions of traditional compositing technology...
June 20, 2017: Nanoscale
https://www.readbyqxmd.com/read/28631581/the-writer-s-guide-to-education-scholarship-in-emergency-medicine-education-innovations-part-3
#10
Andrew K Hall, Carly Hagel, Teresa M Chan, Brent Thoma, Aleisha Murnaghan, Farhan Bhanji
OBJECTIVE: The scholarly dissemination of innovative medical education practices helps broaden the reach of this type of work, allowing scholarship to have an impact beyond a single institution. There is little guidance in the literature for those seeking to publish program evaluation studies and innovation papers. This study aims to derive a set of evidence-based features of high-quality reports on innovations in emergency medicine (EM) education. METHODS: We conducted a scoping review and thematic analysis to determine quality markers for medical education innovation reports, with a focus on EM...
June 20, 2017: CJEM
https://www.readbyqxmd.com/read/28631295/an-em-algorithm-for-nonparametric-estimation-of-the-cumulative-incidence-function-from-repeated-imperfect-test-results
#11
Birgit I Witte, Johannes Berkhof, Marianne A Jonker
In screening and surveillance studies, event times are interval censored. Besides, screening tests are imperfect so that the interval at which an event takes place may be uncertain. We describe an expectation-maximization algorithm to find the nonparametric maximum likelihood estimator of the cumulative incidence function of an event based on screening test data. Our algorithm has a closed-form solution for the combined expectation and maximization step and is computationally undemanding. A simulation study indicated that the bias of the estimator tends to zero for large sample size, and its mean squared error is in general lower than the mean squared error of the estimator that assumes the screening test is perfect...
June 20, 2017: Statistics in Medicine
https://www.readbyqxmd.com/read/28630393/sample-size-re-estimation-without-un-blinding-for-time-to-event-outcomes-in-oncology-clinical-trials
#12
Huang Lihong, Bai Jianling, Yu Hao, Chen Feng
Sample size re-estimation is essential in oncology studies. However, the use of blinded sample size reassessment for survival data has been rarely reported. Based on the density function of the exponential distribution, an expectation-maximization (EM) algorithm of the hazard ratio was derived, and several simulation studies were used to verify its applications. The method had obvious variation in the hazard ratio estimates and overestimation for the relatively small hazard ratios. Our studies showed that the stability of the EM estimation results directly correlated with the sample size, the convergence of the EM algorithm was impacted by the initial values, and a balanced design produced the best estimates...
June 20, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28629288/p53-mutation-and-epigenetic-imprinted-igf2-h19-gene-analysis-in-mesenchymal-stem-cells-derived-from-amniotic-fluid-amnion-endometrium-and-wharton-s-jelly
#13
Tatsanee Phermthai, Puttachart Pokathikorn, Suparat Wichitwiengrat, Sasiprapa Thongbopit, Kittima Tungprasertpol, Suphakde Julavijitphong
Mesenchymal stem cells (MSC) are promising cells for medical therapy. In in vitro expansion, MSC can give rise to progeny with genomic and epigenomic alterations, resulting in senescence, loss terminal differentiation and transformation to cancer. However, MSC genome protects its genetic instability via a guardian function of the P53 tumor suppressor gene and epigenetic balance system during MSC culture. Mutations of P53 and epigenetic alterations have been reported to disrupt the quality and quantity of MSC and initiate tumorigenesis...
June 19, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/28628789/challenges-and-opportunities-in-the-high-resolution-cryo-em-visualization-of-microtubules-and-their-binding-partners
#14
REVIEW
Eva Nogales, Elizabeth H Kellogg
As non-crystallizable polymers, microtubules have been the target of cryo-electron microscopy (cryo-EM) studies since the technique was first established. Over the years, image processing strategies have been developed that take care of the unique, pseudo-helical symmetry of the microtubule. With recent progress in data quality and data processing, cryo-EM reconstructions are now reaching resolutions that allow the generation of atomic models of microtubules and the factors that bind them. These include cellular partners that contribute to microtubule cellular functions, or small ligands that interfere with those functions in the treatment of cancer...
June 16, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28628788/cryo-em-structures-of-human-%C3%AE-secretase
#15
REVIEW
Guanghui Yang, Rui Zhou, Yigong Shi
γ-secretase, a membrane-embedded aspartate protease, catalyzes peptide bond hydrolysis of a large variety of type I integral membrane proteins exemplified by amyloid precursor protein (APP). Cleavage of APP leads to formation of β-amyloid plaque, which is a hallmark of Alzheimer's disease (AD). Over 200 AD-associated mutations are mapped to presenilin 1 (PS1), the catalytic component of γ-secretase. In the past three years, several cryo-electron microscopy (cryo-EM) structures of human γ-secretase have been determined at near atomic resolutions...
June 16, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28628693/understanding-the-role-of-photolyases-photoprotection-and-beyond
#16
Neal Bhatia, Brian Berman, Roger I Ceilley, Leon H Kircik
<p>The limitations of photoprotection modalities have been the inability to arrest the progression of photodamage. Chemoprevention strategies involving a sunscreen has been incomplete because of the need to induce sustained repair of mutations and slow carcinogenesis. Photolyases, or photoreactivation enzymes, serve the role of repairing mutations and damage to DNA induced by ultraviolet (UV) radiation and therefore influence the initiation phases of carcinogenesis. As these enzymes are absent in humans, exogenous forms have been manufactured and are now utilized in topical agents to supplement and augment the innate repair mechanisms that are mostly inefficient...
May 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28628691/eruptive-melanocytic-acral-nevi-in-the-setting-of-6-mercaptopurine-therapy
#17
Arpan V Prabhu, Kristin Bibee, Joseph C English
<p>Eruptive melanocytic nevi (EMN) are a rare clinical finding characterized by sudden-onset nevi that often present in a grouped distribution. They have been associated with chemotherapy, immunosuppression, bullous diseases, and medications including multikinase and BRAF inhibitors. It is important for dermatologists to be able to identify patients with sudden development of new melanocytic nevi secondary to particular medications. Herein, we describe a case of eruptive melanocytic acral nevi secondary to 6-mercaptopurine therapy...
May 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28628690/case-report-of-multiple-keratoacanthomas-and-squamous-cell-carcinomas-in-a-patient-receiving-pembrolizumab
#18
Soham Chaudhari, Argentina Leon, Ethan Levin, Isaac Neuhaus, Wilson Liao
<p>PD-1 is expressed on antigen-stimulated T cells and induces a downstream signaling pathway that works by negative feedback to inhibit T cell proliferation, cytokine release, and cytotoxicity. PD-1 antibodies increase tumor cell killing peripherally and have a role in advanced melanoma treatment. We describe a case of an 84 year old female with stage 4 metastatic melanoma in a trial of the PD-1 inhibitor pembrolizumab who developed multiple keratoacanthomas after several months of treatment. While keratoacanthomas have been reported in patients taking BRAF inhibitors, no such reports exist for those on pembrolizumab, making this the first case report to point out this association for further investigative studies...
May 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28628689/aggressive-skin-cancers-occurring-in-patients-treated-with-the-janus-kinase-inhibitor-ruxolitinib
#19
Adam B Blechman, Christine E Cabell, Christine H Weinberger, Anna Duckworth, Justin J Leitenberger, Fiona O Zwald, Mark A Russell
<p>The Food and Drug Administration approved Ruxolitinib in 2011 for the treatment of primary myelofibrosis. Five-year safety data showed a higher incidence of skin cancer in patients treated with Ruxolitinib compared to best available therapy for myelofibrosis. This report presents a series of five patients with history of myelofibrosis treated with Ruxolitinib who subsequently developed numerous skin cancers with aggressive biological behavior. Each patient in this report was treated by a Mohs surgeon affiliated with an academic institution...
May 1, 2017: Journal of Drugs in Dermatology: JDD
https://www.readbyqxmd.com/read/28628688/effectiveness-of-a-nutraceutical-during-non-ablative-1927-nm-fractional-laser-on-patients-with-facial-hyperpigmentation-and-photoaging
#20
Joely Kaufman-Janette, Alex Cazzaniga, Annelyse Ballin, Rachel Swanson-Garcell
<p>Background: Fractional lasers have been proven to treat hyperpigmentation and photoaging. Little research has been done on the effects of supplements on healing post-laser resurfacing. A nutraceutical could offer the benefit of faster healing of the skin and fewer side effects.</p> <p>Objective: Evaluate the effectiveness of a nutraceutical associated with fractional 1927 nm laser in healing time and effectiveness on hyperpigmentation and photoaging.</p> <p>Methods & Materials: A prospective, randomized, evaluator-blinded, pilot study included Fitzpatrick skin types I-III patients with hyperpigmentation and photoaging randomly assigned to two groups...
May 1, 2017: Journal of Drugs in Dermatology: JDD
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