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https://www.readbyqxmd.com/read/28737935/the-current-state-of-peptide-drug-discovery-back-to-the-future
#1
Antoine Henninot, James C Collins, John M Nuss
Over the last decade, peptide drug discovery has experienced a revival of interest and scientific momentum, as the pharmaceutical industry has come to appreciate the role that peptide therapeutics can play in addressing unmet medical needs, and how this class of compounds can be an excellent complement or even preferable alternative to small molecule and biological therapeutics. In this perspective we give a concise description of the recent progress in peptide drug discovery in a holistic manner, highlighting enabling technological advances affecting nearly every aspect of this field: from lead discovery, to synthesis and optimization, to peptide drug delivery...
July 24, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28737448/mast-cell-and-m1-macrophage-infiltration-and-local-pro-inflammatory-factors-were-attenuated-with-incretin-based-therapies-in-obesity-related-glomerulopathy
#2
Jiao He, Geheng Yuan, Fangxiao Cheng, Junqing Zhang, Xiaohui Guo
BACKGROUND: The global increase of obesity parallels the obesity-related glomerulopathy (ORG) epidemic. Dipeptidyl peptidase 4 inhibitors and glucagon-like peptide-1 receptor agonists were well recognized to attenuate renal injury independent of glucose control in diabetic nephropathy. There are limited studies focusing on their effects on ORG. We explored the effects of incretin-based therapies on early ORG and the inflammatory responses involved mainly concentrated on mast cell (MC) and macrophage (M) infiltration and local pro-inflammatory factors...
July 24, 2017: Metabolic Syndrome and related Disorders
https://www.readbyqxmd.com/read/28737021/infection-therapy-the-problem-of-drug-resistance-and-possible-solutions
#3
Harald Brüssow
The rising antibiotic resistance in major bacterial pathogens together with the breakdown of the antibiotic discovery platform creates a critical situation for infection therapy. Recent developments reviving new antibiotic discovery from defining chemical rules for membrane-passing compounds to isolation chips for soil bacteria and exploring the human microbiome for antibiotic-producing bacteria are discussed. The potential of bacteriocins, tailocins, phage lysins, phages, probiotics and commensal blends as alternatives to antibiotics is evaluated...
July 24, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28732395/microalgae-bacteria-models-evolution-from-microalgae-steady-state-to-integrated-microalgae-bacteria-wastewater-treatment-models-a-comparative-review
#4
REVIEW
Alessandro Solimeno, Joan García
The search for environmentally neutral alternative fuels had revived the interest for microalgae-bacteria wastewater treatment systems. The potential achieving of bioproducts from microalgae biomass has also greatly contributed. The reactions that occur in these systems are complex, and the degree of scientific knowledge is still scarce compared to that of conventional bacteria wastewater treatments. Mathematical models offer a great opportunity to study the simultaneous effect of the multiple factors affecting microalgae and bacteria, thus allowing for the prediction of final biomass production, and contributing to the system design optimization in terms of operation and control...
July 17, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28725387/origins-of-two-hemiclonal-hybrids-among-three-hexagrammos-species-teleostei-hexagrammidae-genetic-diversification-through-host-switching
#5
Hiroyuki Munehara, Miho Horita, Motoko R Kimura-Kawaguchi, Aya Yamazaki
Two natural, hemiclonal hybrid strains were discovered in three Hexagrammos species. The natural hybrids, all of which were females that produced haploid eggs containing only the Hexagrammos octogrammus genome (maternal ancestor; hereafter Hoc), generated F1 hybrid-type offspring by fertilization with haploid sperm of Hexagrammos agrammus or Hexagrammos otakii (paternal species; Hag and Hot, respectively). This study was performed to clarify the extent of diversification between the two hybrids and the maternal ancestor...
October 2016: Ecology and Evolution
https://www.readbyqxmd.com/read/28724254/effects-of-calcium-on-the-performance-bacterial-population-and-microbial-metabolism-of-a-denitrifying-phosphorus-removal-system
#6
Hongliang Dai, Yifeng Wu, Lihong Peng, Zheqin Dai, Xiang Li, Xiwu Lu
A sequencing batch reactor was operated to study the effects of influent Ca(2+) on the efficiency, bacterial population, and microbial metabolism of denitrifying phosphorus removal system. Results showed that high Ca(2+) loading (≥80mg/L) significantly inhibited the performance of simultaneous nitrogen and phosphorus removal. The abundance of phosphorus removal-related organisms (Dechloromonas and Candidatus Accumulibacter) decreased with increasing Ca(2+) concentration from 20 to 140mg/L, while the abundance of glycogen-accumulating organisms and other bacteria increased...
July 8, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28716289/devic-s-disease-before-devic-on-the-contribution-of-friedrich-albin-schanz-1863-1923
#7
S Jarius, B Wildemann
Neuromyelitis optica (NMO, Devic's disease) is an autoimmune disorder of the CNS that mainly affects the optic nerves and spinal cord and, if not treated, can leave patients blind and wheelchair-bound. NMO was long considered a clinical variant of multiple sclerosis (MS). While the history of MS has been studied extensively, relatively little is known about the early history of NMO. A dissertation written by Fernand Gault (1873-1936), a doctoral student to Eugène Devic (1858-1930), a Lyon-based neurologist after whom the disease would later be named, is considered by many the first review of NMO...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28711284/financialisation-in-health-care-an-analysis-of-private-equity-fund-investments-in-turkey
#8
Ipek Eren Vural
The 2007-2008 global financial crisis revived interest in the impacts of financial markets and actors on our social and economic life. Nevertheless, research on health care financialisation remains scant. This article presents findings from research on one modality of financial investments in health care: global private equity funds' investments in private hospitals. Adopting a political economy approach, it analyses the drivers and impacts of the upsurge of global private equity investments in the Turkish private hospital sector amid the global financial crisis...
June 9, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/28709374/nanoparticles-as-efflux-pump-and-biofilm-inhibitor-to-rejuvenate-bactericidal-effect-of-conventional-antibiotics
#9
REVIEW
Divya Gupta, Ajeet Singh, Asad U Khan
The universal problem of bacterial resistance to antibiotic reflects a serious threat for physicians to control infections. Evolution in bacteria results in the development of various complex resistance mechanisms to neutralize the bactericidal effect of antibiotics, like drug amelioration, target modification, membrane permeability reduction, and drug extrusion through efflux pumps. Efflux pumps acquire a wide range of substrate specificity and also the tremendous efficacy for drug molecule extrusion outside bacterial cells...
December 2017: Nanoscale Research Letters
https://www.readbyqxmd.com/read/28705869/auditory-cortex-interneuron-development-requires-cadherins-operating-hair-cell-mechanoelectrical-transduction
#10
Baptiste Libé-Philippot, Vincent Michel, Jacques Boutet de Monvel, Sébastien Le Gal, Typhaine Dupont, Paul Avan, Christine Métin, Nicolas Michalski, Christine Petit
Many genetic forms of congenital deafness affect the sound reception antenna of cochlear sensory cells, the hair bundle. The resulting sensory deprivation jeopardizes auditory cortex (AC) maturation. Early prosthetic intervention should revive this process. Nevertheless, this view assumes that no intrinsic AC deficits coexist with the cochlear ones, a possibility as yet unexplored. We show here that many GABAergic interneurons, from their generation in the medial ganglionic eminence up to their settlement in the AC, express two cadherin-related (cdhr) proteins, cdhr23 and cdhr15, that form the hair bundle tip links gating the mechanoelectrical transduction channels...
July 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28705361/changing-perceived-importance-of-religion-in-mainland-china-1990-2012-an-age-period-cohort-analysis
#11
Anning Hu
The comprehensive social reform and relaxation of religious regulation in mainland China have encouraged scholars to propose a revival thesis of religion, predicting a rising prevalence of religious adherence in the Reform Era. This study extends the revival thesis by focusing attention on people's subjective religiosity, and investigates age, period, and cohort effects on the transition in perceived importance of religion from 1990 to 2012. Capitalizing on the repeated cross-sectional data of the China sample in the World Values Survey, this study shows that (1) The senior population, relative to the younger counterpart, attaches greater importance to religion...
August 2017: Social Science Research
https://www.readbyqxmd.com/read/28704688/occurrences-biosynthesis-and-properties-of-aurones-as-high-end-evolutionary-products
#12
REVIEW
Benjamin Boucherle, Marine Peuchmaur, Ahcène Boumendjel, Romain Haudecoeur
Recent years have witnessed a considerable renewed interest for the uncommon flavonoid class of aurones. The characterization of two major biosynthetic machineries involved in their biosynthesis in flowers has encouraged the revival of phytochemical studies and identification of original structures, a process started almost seventy-five years ago. This review draws up an exhaustive map of natural occurrences of aurones their biosynthetic pathways and roles, with the aim to link their original structural properties among flavonoids to their place in evolution and the selective advantages they bring to some of the most advanced taxa in the plant kingdom...
July 10, 2017: Phytochemistry
https://www.readbyqxmd.com/read/28701416/eukaryotic-transcription-factors-paradigms-of-protein-intrinsic-disorder
#13
REVIEW
Lasse Staby, Charlotte O'Shea, Martin Willemoës, Frederik Theisen, Birthe B Kragelund, Karen Skriver
Gene-specific transcription factors (TFs) are key regulatory components of signaling pathways, controlling, for example, cell growth, development, and stress responses. Their biological functions are determined by their molecular structures, as exemplified by their structured DNA-binding domains targeting specific cis-acting elements in genes, and by the significant lack of fixed tertiary structure in their extensive intrinsically disordered regions. Recent research in protein intrinsic disorder (ID) has changed our understanding of transcriptional activation domains from 'negative noodles' to ID regions with function-related, short sequence motifs and molecular recognition features with structural propensities...
July 12, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28692059/air-stable-and-freestanding-lithium-alloy-graphene-foil-as-an-alternative-to-lithium-metal-anodes
#14
Jie Zhao, Guangmin Zhou, Kai Yan, Jin Xie, Yuzhang Li, Lei Liao, Yang Jin, Kai Liu, Po-Chun Hsu, Jiangyan Wang, Hui-Ming Cheng, Yi Cui
Developing high-capacity anodes is a must to improve the energy density of lithium batteries for electric vehicle applications. Alloy anodes are one promising option, but without pre-stored lithium, the overall energy density is limited by the low-capacity lithium metal oxide cathodes. Recently, lithium metal has been revived as a high-capacity anode, but faces several challenges owing to its high reactivity and uncontrolled dendrite growth. Here, we show a series of Li-containing foils inheriting the desirable properties of alloy anodes and pure metal anodes...
July 10, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28686451/revival-of-the-intermolecular-nuclear-overhauser-effect-for-mapping-local-protein-hydration-dynamics
#15
Daniel Braun, Michael Schmollngruber, Othmar Steinhauser
The highly heterogeneous hydration dynamics of protein-water interfaces is considered important for protein stability and dynamics, protein folding, enzymatic activity, and even drug design. The nuclear Overhauser effect (NOE) between protein and water protons is the only experimental observable which, in principle, can provide a map of locally resolved hydration dynamics. However, its utility was questioned in various theoretical studies that emphasized the contributions of long-range NOE interactions. We show by a detailed analysis based on molecular dynamics simulations that, contrary to recent claims, the protein-water NOE is an excellent observable to map local hydration dynamics at the protein surface...
July 12, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28679221/revival-of-oscillations-from-deaths-in-diffusively-coupled-nonlinear-systems-theory-and-experiment
#16
Wei Zou, Michael Sebek, István Z Kiss, Jürgen Kurths
Amplitude death (AD) and oscillation death (OD) are two structurally different oscillation quenching phenomena in coupled nonlinear systems. As a reverse issue of AD and OD, revival of oscillations from deaths attracts an increasing attention recently. In this paper, we clearly disclose that a time delay in the self-feedback component of the coupling destabilizes not only AD but also OD, and even the AD to OD transition in paradigmatic models of coupled Stuart-Landau oscillators under diverse death configurations...
June 2017: Chaos
https://www.readbyqxmd.com/read/28675916/-termination-of-reimbursement-of-arthroscopy-in-osteoarthritis-of-the-knee-is-this-decision-based-on-scientific-grounds
#17
Thoralf Randolph Liebs, Steffen Berger
Background In Germany, arthroscopy of the knee used to be an accepted procedure in the treatment of osteoarthritis of the knee. However, as of April 1, 2016 reimbursement for this procedure has been discontinued. This was a decision of the Joint Federal Committee (Gemeinsamer Bundesausschuss, G-BA). That decision was based on a report of the German Institute for Quality and Efficiency in Health Care (IQWiG). This report is essentially based on a few studies, three of which have been published in the renowned New England Journal of Medicine...
July 4, 2017: Zeitschrift Für Orthopädie und Unfallchirurgie
https://www.readbyqxmd.com/read/28675422/reviving-cochrane-s-contribution-to-evidence-based-medicine-bridging-the-gap-between-evidence-of-efficacy-and-evidence-of-effectiveness-and-cost-effectiveness
#18
Jack E James
Evidence-based medicine (EBM) has been widely adopted as the main means for transforming medical practice informed by individual practitioner experience to that informed by science. Yet, as a movement for comprehensive change, EBM has not been as transformative as had been widely anticipated. Evidence of clinical efficacy is often organized hierarchically with the randomized controlled trial located towards the apex of an imaginary pyramid. This familiar hierarchy of evidence in medical education, practice, and science serves to guide evaluations of the internal validity of randomized controlled trials, thereby establishing the "efficacy" of clinical interventions...
July 4, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28671051/autobiographical-memory-functions-of-nostalgia-in-comparison-to-rumination-and-counterfactual-thinking-similarity-and-uniqueness
#19
Wing-Yee Cheung, Tim Wildschut, Constantine Sedikides
We compared and contrasted nostalgia with rumination and counterfactual thinking in terms of their autobiographical memory functions. Specifically, we assessed individual differences in nostalgia, rumination, and counterfactual thinking, which we then linked to self-reported functions or uses of autobiographical memory (Self-Regard, Boredom Reduction, Death Preparation, Intimacy Maintenance, Conversation, Teach/Inform, and Bitterness Revival). We tested which memory functions are shared and which are uniquely linked to nostalgia...
July 1, 2017: Memory
https://www.readbyqxmd.com/read/28665694/surveying-the-opinions-of-pennsylvania-chiefs-of-police-toward-officers-carrying-and-administering-naloxone
#20
Paul A Smyser, Jeffrey S Lubin
BACKGROUND: Recent legislation in Pennsylvania allows police officers to administer naloxone to individuals in an opioid overdose. Pressure has subsequently been placed on police departments to adopt naloxone programs. OBJECTIVE: To survey Pennsylvania Chiefs of Police regarding potential obstacles to officer-administered naloxone, and their overall opinion toward such programs. METHODS: A confidential survey was administered at the Annual Conference for the Pennsylvania Chiefs of Police Association and online over the organization's listserv...
June 30, 2017: American Journal of Drug and Alcohol Abuse
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