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https://www.readbyqxmd.com/read/28636417/a-novel-antimicrobial-approach-based-on-the-inhibition-of-zinc-uptake-in-salmonella-enterica
#1
Andrea Battistoni, Serena Ammendola, Emilia Chiancone, Andrea Ilari
In this review we discuss evidences suggesting that bacterial zinc homeostasis represents a promising target for new antimicrobial strategies. The ability of the gut pathogen Salmonella enterica sv Typhimurium to withstand the host responses aimed at controlling growth of the pathogen critically depends on the zinc importer ZnuABC. Strains lacking a functional ZnuABC or its soluble component ZnuA display a dramatic loss of pathogenicity, due to a reduced ability to express virulence factors; withstand the inflammatory response; and compete with other gut microbes...
June 21, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28636389/tumor-microenvironment-responsive-multistaged-nanoplatform-for-systemic-rnai-and-cancer-therapy
#2
Xiaoding Xu, Phei Er Saw, Wei Tao, Yujing Li, Xiaoyuan Ji, Mikyung Yu, Morteza Mahmoudi, Jonathan Rasmussen, Dana Ayyash, Yuxiao Zhou, Omid C Farokhzad, Jinjun Shi
While RNA interference (RNAi) therapy has demonstrated significant potential for cancer treatment, effective and safe systemic delivery of RNAi agents such as small interfering RNA (siRNA) into tumor cells in vivo remains challenging. We herein reported a unique multistaged siRNA delivery nanoparticle (NP) platform, which is comprised of (i) a polyethylene glycol (PEG) surface shell, (ii) a sharp tumor microenvironment (TME) pH-responsive polymer that forms the NP core, and (iii) charge-mediated complexes of siRNA and tumor cell-targeting- and penetrating-peptide-amphiphile (TCPA) that are encapsulated in the NP core...
June 21, 2017: Nano Letters
https://www.readbyqxmd.com/read/28636354/rational-design-of-lithium-sulfur-battery-cathodes-based-on-experimentally-determined-maximum-active-material-thickness
#3
Michael J Klein, Gabriel M Veith, Arumugam Manthiram
Rational design of conductive carbon hosts for high energy density lithium-sulfur batteries requires an understanding of the fundamental limitations to insulating active material loading. In this work, we investigate the electrochemistry of lithium sulfide films ranging in thickness from 30 to 3500 nm. We show that films thicker than approximately 40 nm cannot be charged at local charge densities above 1 μA cm-2, and by implication, the maximum useful pore diameter is near 60 nm in a practical cathode. 'Activation' overpotentials for Li2S are identified in thicker films, resulting from polysulfide generation, but are shown not to improve the fundamental areal charge limitations...
June 21, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28636323/ultrafast-dynamic-pressure-sensors-based-on-graphene-hybrid-structure
#4
Shanbiao Liu, Xing Wu, Dongdong Zhang, Congwei Guo, Peng Wang, Weida Hu, Xinming Li, Xiaofeng Zhou, Hejun Xu, Chen Luo, Jian Zhang, Jun-Hao Chu
The development of artificial skin is drawing tremendous attention due to its potential applications in sensing a variety of physical quantities, such as tactility, vibration, and temperature. A strain sensor that can mimic and surpass the subtle pressure-sensing properties of natural skin requires rational material design and array-accessible devices. Here, we report a new and facile preparation of a graphene hybrid structure with an ultrafast dynamic pressure response. Graphene oxide nanosheets are used as a surfactant to prevent graphene restacking in aqueous solution...
June 21, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28636281/aryl-and-heteroaryl-substituted-phenylalanines-as-ampa-receptor-ligands
#5
Ewa Szymańska, Paulina Chałupnik, Tommy N Johansen, Birgitte Nielsen, Ana Maria Cuñado Moral, Darryl S Pickering, Anna Więckowska, Katarzyna Kieć-Kononowicz
A series of racemic unnatural amino acids was rationally designed on the basis of recently published X-ray structures of the GluA2 LBD with bound phenylalanine-based antagonists. Twelve new diaryl- or aryl/heteroaryl-substituted phenylalanine derivatives were synthesized and evaluated in vitro in radioligand binding assays at native rat ionotropic glutamate receptors. The most interesting compound in this series, (RS)-2-amino-3-(3'-hydroxy-5-(1H-pyrazol-4-yl)-[1,1'-biphenyl]-3-yl)propanoic acid 7e, showed the binding affinity of 4...
June 21, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28636269/commentary-on-r-d-trends-away-from-general-medicine-cardiovascular-drugs-can-the-fda-help-reverse-the-trend
#6
R J Meyer
In the latter part of the 20th century, drug development in cardiovascular diseases (CVDs) was a paragon of "modern" therapeutics, bringing about a substantial number of effective, well-tolerated agents targeting some of the most prevalent diseases of the Western world. These drugs were often examples of rational drug development targeting specific pathophysiologic pathways previously elucidated through basic research (e.g., targeting of the renin-angiotensin system or the cholesterol synthesis pathway). The widespread adoption of these ground-breaking medications in practice and into medical guidelines undoubtedly played a role in the fall of morbidity and mortality from CVD in the United States in recent decades...
June 21, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28635378/people-with-autism-spectrum-conditions-make-more-consistent-decisions
#7
George D Farmer, Simon Baron-Cohen, William J Skylark
People with autism spectrum conditions (ASC) show reduced sensitivity to contextual stimuli in many perceptual and cognitive tasks. We investigated whether this also applies to decision making by examining adult participants' choices between pairs of consumer products that were presented with a third, less desirable "decoy" option. Participants' preferences between the items in a given pair frequently switched when the third item in the set was changed, but this tendency was reduced among individuals with ASC, which indicated that their choices were more consistent and conventionally rational than those of control participants...
June 1, 2017: Psychological Science
https://www.readbyqxmd.com/read/28635336/new-advances-in-focal-therapy-for-early-stage-prostate-cancer
#8
Kae Jack Tay, Ariel A Schulman, Christina Sze, Efrat Tsivian, Thomas J Polascik
Prostate focal therapy offers men the opportunity to achieve oncological control while preserving sexual and urinary function. The prerequisites for successful focal therapy are to accurately identify, localize and completely ablate the clinically significant cancer(s) within the prostate. We aim to evaluate the evidence for current and upcoming technologies that could shape the future of prostate cancer focal therapy in the next five years. Areas Covered: Current literature on advances in patient selection using imaging, biopsy and biomarkers, ablation techniques and adjuvant treatments for focal therapy are summarized...
June 21, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28635262/enormous-hydrogen-bond-strength-enhancement-through-%C3%AF-conjugation-gain-implications-for-enzyme-catalysis
#9
Chia-Hua Wu, Keigo Ito, Allyson Buytendyk, Kit Hansell Bowen, Judy I Wu
Surprisingly large "resonance-assistance" effects may explain how some enzymes form extremely short, strong hydrogen bonds to stabilize reactive oxyanion intermediates and facilitate catalysis. Computational models for several enzymic residue-substrate interactions reveal that when a π-conjugated, proton donor (XH) forms a hydrogen bond to a charged substrate (Y-), XH can become significantly more π-electron delocalized, and this "extra" stabilization may boost the [XH…Y-] hydrogen bond strength by up to 15 kcal/mol...
June 21, 2017: Biochemistry
https://www.readbyqxmd.com/read/28635260/development-validation-and-inter-laboratory-evaluation-of-a-quantitative-multiplexing-method-to-assess-levels-of-ten-endogenous-allergens-in-soybean-seed-and-its-application-to-field-trials-spanning-three-growing-seasons
#10
Ryan Christopher Hill, Trent J Oman, Xiujuan Wang, Guomin Shan, Barry Schafer, Rod A Herman, Rowel Tobias, Jeff Shippar, Bhaskar Malayappan, Li Sheng, Austin Xu, Jason Bradshaw
As part of the regulatory approval process in Europe, comparison of endogenous soybean allergen levels between genetically engineered (GE) and non-GE plants has been requested. A quantitative multiplex analytical method using tandem mass spectrometry has been developed and validated to measure ten potential soybean allergens from soybean seed. The analytical method was implemented at six laboratories to demonstrate the robustness of the method and further applied to three soybean field studies across multiple growing seasons (including 21 non-GE soybean varieties) to assess the natural variation of allergen levels...
June 21, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28635215/-retrospective-comparison-of-screening-criteria-for-active-surveillance-for-papillary-thyroid-microcarcinoma
#11
K Qian, T Q Sun, K Guo, X K Zheng, D S Li, W W Wei, Y Wu, Q H Ji, Z Y Wang
Objective: To investigate the rationality of management of active surveillance for papillary thyroid microcarcinoma (PTMC) and the main indications for active surveillance for PTMC. Methods: In this study, two criteria were used to evaluate patients with PTMC: low-risk PTMC conditions defined by Kuma hospital and Chinese Association of Thyroid Oncology (CATO) consensus on PTMC management of active surveillance. The patients had received surgical treatment. Clinicopathological characteristics and prognosis of the patients in different groups were compared...
June 7, 2017: Zhonghua Er Bi Yan Hou Tou Jing Wai Ke za Zhi, Chinese Journal of Otorhinolaryngology Head and Neck Surgery
https://www.readbyqxmd.com/read/28635187/the-viologen-cation-radical-pimer-a-case-of-dispersion-driven-bonding
#12
Margarita Geraskina, Andrew S Dutton, Mark Juetten, Samuel Wood, Arthur Winter
Pi bonds between organic radicals have generated recent excitement as an orthogonal interaction for designing self-assembling architectures in water. Here, we provide the first a systematic investigation of the effect of the viologen cation radical structure on the strength and nature of the pimer bond. A striking and unexpected feature of the this pi bond is that the bond strength is unchanged by substitution with electron-donating groups or withdrawing groups or with increased conjugation. Furthermore, the interaction is undiminished by sterically bulky N-alkyl groups...
June 20, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28635152/a-novel-dna-structure-containing-agi-mediated-g-g-and-c-c-base-pairs
#13
Hehua Liu, Fusheng Shen, Phensinee Haruehanroengra, Qingqing Yao, Yunshan Cheng, Yiqing Chen, Chun Yang, Jing Zhang, Baixing Wu, Qiang Luo, Ruixue Cui, Jixi Li, Jinbiao Ma, Jia Sheng, Jianhua Gan
Metallo-base pairs have been extensively utilized in many research fields, including genetic code extension, novel therapeutics development, and various nanodevice designs. Compared to other cations, AgI is more flexible in pairing with natural base pairs. Herein, we present a DNA structure containing two C-AgI-C pairs and one first time reported G-AgI-G pair in a short 8mer DNA strand. This structure not only discloses the detailed insights into these AgI-base pairing patterns in DNA, but also represents the first nonhelical DNA structure driven by the heavy metal ions, further contributing to the structural diversity of DNA...
June 20, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28635079/oxygen-vacancy-mediated-photocatalysis-of-biocl-reactivity-selectivity-and-perspective
#14
Hao Li, Jie Li, Zhihui Ai, Falong Jia, Lizhi Zhang
Semiconductor photocatalysis is a trustworthy approach to harvest clean solar light for energy conversions, while state-of-the-art catalytic efficiencies are unsatisfactory because of the finite light response and/or robust charge carriers' recombination. Along with the development of modern material characterization techniques and electronic-structure computations, oxygen vacancies (OVs) on real photocatalysts surface, even in infinitesimal concentration, are found to play a more decisive role in determining the kinetics, energetics and mechanisms of photocatalytic reactions...
June 20, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/28634837/heterocyclic-quinodimethanes
#15
REVIEW
Xueliang Shi, Chunyan Chi
This chapter describes a series of heterocyclic quinodimethanes mainly containing O, N, S and Si atoms in their frameworks with either closed- or open-shell electronic structures in the ground state. Their syntheses, structural characterizations and chemical and physical properties are comprehensively reviewed. Some of them are used as materials for dyes/pigments and semiconductors for organic electronics. Some of them show an open-shell singlet diradical character with unusual properties. The purpose of this chapter is to provide fundamental understanding on the structure-property relationships of quinoidal π-conjugated compounds and give some insight into the rational design of such molecules with desirable properties...
August 2017: Topics in Current Chemistry (Journal)
https://www.readbyqxmd.com/read/28634816/critical-biological-parameters-modulate-affinity-as-a-determinant-of-function-in-t-cell-receptor-gene-modified-t-cells
#16
Timothy T Spear, Yuan Wang, Kendra C Foley, David C Murray, Gina M Scurti, Patricia E Simms, Elizabeth Garrett-Mayer, Lance M Hellman, Brian M Baker, Michael I Nishimura
T-cell receptor (TCR)-pMHC affinity has been generally accepted to be the most important factor dictating antigen recognition in gene-modified T-cells. As such, there is great interest in optimizing TCR-based immunotherapies by enhancing TCR affinity to augment the therapeutic benefit of TCR gene-modified T-cells in cancer patients. However, recent clinical trials using affinity-enhanced TCRs in adoptive cell transfer (ACT) have observed unintended and serious adverse events, including death, attributed to unpredicted off-tumor or off-target cross-reactivity...
June 20, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28634769/decision-making-capacity-and-unusual-beliefs-two-contentious-cases-australasian-association-of-bioethics-and-health-law-john-mcphee-law-student-essay-prize-2016
#17
Brent Hyslop
Decision-making capacity is a vital concept in law, ethics, and clinical practice. Two legal cases where capacity literally had life and death significance are NHS Trust v Ms T [2004] and Kings College Hospital v C [2015]. These cases share another feature: unusual beliefs. This essay will critically assess the concept of capacity, particularly in relation to the unusual beliefs in these cases. Firstly, the interface between capacity and unusual beliefs will be examined. This will show that the "using and weighing of information" is the pivotal element in assessment...
June 20, 2017: Journal of Bioethical Inquiry
https://www.readbyqxmd.com/read/28634057/evaluation-of-the-biotechnological-potential-of-a-novel-purified-protease-bs1-from-bacillus-safensis-s406-on-the-chitin-extraction-and-detergent-formulation
#18
Samiha Mhamdi, Intidhar Bkhairia, Rim Nasri, Tahar Mechichi, Moncef Nasri, Alya Sellami Kamoun
The aim of this study is the production of High-Added Value enzyme for Industrial Uses. An extracellular alkaline stable protease BS1 was purified from a newly bacterium, Bacillus safensis S406, isolated from the Sfax Solar Saltern. BS1 was purified by a process involving sulfate d'ammonium sulfate precipitation, sephadex G-75, Mono-Q anion-exchange chromatography and ultrafiltation. The enzyme has a molecular weight of 24kDa and appeared as a single band on native-PAGE. The optimum pH and temperature values of its proteolytic activity were pH 11...
June 17, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28633926/synergic-stimulation-of-serotonin-5-ht1a-receptor-and-%C3%AE-2-adrenoceptors-for-neuropathic-pain-relief-preclinical-effects-of-2-substituted-imidazoline-derivatives
#19
Lorenzo Di Cesare Mannelli, Carla Ghelardini, Laura Micheli, Fabio Del Bello, Mario Giannella, Alessandro Piergentili, Wilma Quaglia
Neuropathic pain affects millions of people causing disability and impairing quality of life. Commonly used analgesics are generally characterized by limited therapeutic outcomes. The serotonin 5-HT1A receptor and the α2 adrenergic receptors are involved in central nociceptive mechanisms with a pivotal role in the inhibitory descending pain pathway. Since their stimulation may modulate the nervous signaling altered by neuropathies, the purpose of the present research is the study of the combined activation of 5-HT1A and α2 receptors by rationally designed imidazoline ligands ((S)-1 and 2-5) in a rat model of neuropathic pain (chronic constriction injury - CCI)...
June 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28633875/rational-drug-loading-of-liposomes-revisited
#20
EDITORIAL
Kinam Parak
No abstract text is available yet for this article.
April 28, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
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