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https://www.readbyqxmd.com/read/29244501/origins-of-enzyme-catalysis-experimental-findings-for-c-h-activation-new-models-and-their-relevance-to-prevailing-theoretical-constructs
#1
Judith P Klinman, Adam R Offenbacher, Shenshen Hu
The physical basis for enzymatic rate accelerations is a subject of great fundamental interest and of direct relevance to areas that include the de novo design of green catalysts and the pursuit of new drug regimens. Extensive investigations of C-H activating systems have provided considerable insight into the relationship between an enzyme's overall structure and the catalytic chemistry at its active site. This Perspective highlights recent experimental data for two members of distinct, yet iconic C-H activation enzyme classes, lipoxygenases and prokaryotic alcohol dehydrogenases...
December 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29244109/gadd45a-promotes-active-dna-demethylation-of-the-mmp-9-promoter-via-base-excision-repair-pathway-in-ages-treated-keratinocytes-and-in-diabetic-male-rat-skin
#2
Liyan Zhou, Wei Wang, Chuan Yang, Tingting Zeng, Mengdie Hu, Xiaoyi Wang, Na Li, Kan Sun, Chuan Wang, Jing Zhou, Meng Ren, Li Yan
Diabetes elevates matrix metalloproteinase-9 (MMP-9) levels in the skin and its keratinocytes, and activated MMP-9 impairs skin wound healing. Epigenetic regulation of the DNA methylation status within the MMP-9 promoter plays an important role in the alteration of MMP-9 expression. Our aim was to investigate the role and mechanism of growth arrest and DNA damage-inducible 45a (GADD45a), a well-known DNA demethylation regulatory protein that mediates DNA methylation, in the regulation of MMP-9 expression. In this study, we showed that GADD45a was markedly upregulated in skin tissues from patients with diabetic foot ulcers, in diabetic rats and in human keratinocyte (HaCaT) cells exposed to advanced glycation end products (AGEs)...
December 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/29244009/inference-of-genetic-relatedness-between-viral-quasispecies-from-sequencing-data
#3
Olga Glebova, Sergey Knyazev, Andrew Melnyk, Alexander Artyomenko, Yury Khudyakov, Alex Zelikovsky, Pavel Skums
BACKGROUND: RNA viruses such as HCV and HIV mutate at extremely high rates, and as a result, they exist in infected hosts as populations of genetically related variants. Recent advances in sequencing technologies make possible to identify such populations at great depth. In particular, these technologies provide new opportunities for inference of relatedness between viral samples, identification of transmission clusters and sources of infection, which are crucial tasks for viral outbreaks investigations...
December 6, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29243807/microrna-as-a-systemic-intervention-in-the-specific-breast-cancer-subtypes-with-c-myc-impacts-introducing-subtype-based-appraisal-tool
#4
REVIEW
Vida Pourteimoor, Mahdi Paryan, Samira Mohammadi-Yeganeh
Breast cancer is indisputably a heterogeneous disease, in which a formidable combination of definitely dis-regulated C-MYC and microRNA (miRNA) profiles along with other factors are responsible to generate a specific type of breast cancer. C-MYC as a master regulator of more than 20,000 genes can modify the expression of genes underlying to perform diverse conflicting functional frameworks. The functional spectra of miRNA in the new areas of the evolution of cell behaviors are identified. Here, we endeavor to summarize some recent advances of miRNA applications that can be recruited as combinatorial targeted therapy for patients with breast cancer...
December 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29243741/impact-of-copy-neutral-loss-of-heterozygosity-and-total-genome-aberrations-on-survival-in-myelodysplastic-syndrome
#5
Cecilia C S Yeung, Scott McElhone, Xue Yan Chen, David Ng, Barry E Storer, H Joachim Deeg, Min Fang
Myelodysplastic syndromes (MDS) are a heterogeneous group of diseases with varying genetic aberrations. Half of MDS patients have normal karyotype, obscuring the underlying condition indicating a need for new markers for improved diagnostics and prognosis. We performed a retrospective review of sequential MDS patients who underwent chromosomal genetic array testing (CGAT) between November 2008 and March 2014. Total Genomic Aberration (TGA) scores, with and without copy-neutral loss of heterozygosity (cnLOH), were compared to pathology and clinical data...
December 15, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29243735/orbital-decompression-for-thyroid-eye-disease-methods-outcomes-and-complications
#6
J M Jefferis, R K Jones, Z I Currie, J H Tan, S M Salvi
PurposeTo determine the safety and effectiveness of orbital decompression for thyroid eye disease (TED) in our unit. To put this in the context of previously published literature.Patients and methodsA retrospective case review of all patients undergoing orbital decompression for TED under the care of one orbital surgeon (SMS) between January 2009 and December 2015. A systematic literature review of orbital decompression for TED.ResultsWithin the reviewed period, 93 orbits of 55 patients underwent decompression surgery for TED...
December 15, 2017: Eye
https://www.readbyqxmd.com/read/29243581/anticancer-natural-coumarins-as-lead-compounds-for-the-discovery-of-new-drugs
#7
Diana C G A Pinto, Artur M S Silva
Cancer is one of the most serious illnesses of our civilization. The International Agency for Research on Cancer estimated that 14.1 million new cancer cases were diagnosed. Therefore, the cure efficiency of cancer chemotherapy depends not only on how the anticancer drug is delivered to its targets but also on the anticancer drug itself. Among the approved drugs 80% are derived from natural compounds. In this sense, coumarins, natural polyphenols for which anticancer activity has been proved, can be a source or inspire the synthesis of new anticancer agents...
December 14, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29243579/recent-development-of-coumarin-derivatives-as-potential-antiplasmodial-and-antimalarial-agents
#8
Xin-Liang Hu, Chuan Gao, Zhi Xu, Ming-Liang Liu, Lian-Shun Feng, Guang-De Zhang
Malaria still remains one of the leading deadliest diseases throughout the world, leading to around 1 million deaths annually. The emergence and spread of growing resistance to the first-line antimalarials, alarming the serious problem in malaria control and demanding the need for new drugs more potent than earlier with improved absorption, distribution, metabolism, and excretion (ADME) profiles. Coumarins, which exhibited various biological properties, also displayed potential in vitro antiplasmodial and in vivo antimalarial activities...
December 14, 2017: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/29243558/ex-vivo-and-in-vivo-genome-editing-a-regulatory-scientific-framework-from-early-development-to-clinical-implementation
#9
Houria Bachtarzi
Recent advances in human genome science have paved the way to a new class of human gene therapies based on gene editing, with the potential to provide a long-lasting curative strategy for many debilitating and complex disorders, for which there is an unmet medical need. Therapeutic genome editing encompasses both ex vivo and in vivo gene correction modalities, for which similar and also application-specific considerations apply, which dictate the overall strategy to be followed from a scientific, clinical and regulatory perspective...
December 15, 2017: Regenerative Medicine
https://www.readbyqxmd.com/read/29243546/changes-in-medication-use-in-a-cohort-of-patients-with-advanced-cancer-the-international-multicentre-prospective-european-palliative-care-cancer-symptom-study
#10
Kristel Paque, Monique Elseviers, Robert Vander Stichele, Koen Pardon, Marianne J Hjermstad, Stein Kaasa, Tinne Dilles, Martine De Laat, Simon Van Belle, Thierry Christiaens, Luc Deliens
BACKGROUND: Information on medication use in the last months of life is limited. AIM: To describe which medications are prescribed and deprescribed in advanced cancer patients receiving palliative care in relation to time before death and to explore associations with demographic variables. DESIGN: Prospective study, using case report forms for monthly data collection. Medication included cancer treatment and 19 therapeutic groups, grouped into four categories for: (1) cancer therapy, (2) specific cancer-related symptom relief, (3) other symptom relief and (4) long-term prevention...
December 1, 2017: Palliative Medicine
https://www.readbyqxmd.com/read/29243483/relative-binding-free-energy-calculations-in-drug-discovery-recent-advances-and-practical-considerations
#11
Zoe Cournia, Bryce Allen, Woody Sherman
Accurate in silico prediction of protein-ligand binding affinities has been a primary objective of structure-based drug design for decades due to the putative value it would bring to the drug discovery process. However, computational methods have historically failed to deliver value in real-world drug discovery applications due to a variety of scientific, technical, and practical challenges. Recently, a family of approaches commonly referred to as relative binding free energy (RBFE) calculations, which rely on physics-based molecular simulations and statistical mechanics, have shown promise in reliably generating accurate predictions in the context of drug discovery projects...
December 15, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29243413/clinical-response-to-apatinib-monotherapy-in-advanced-non-small-cell-lung-cancer
#12
Jianping Xu, Xiaoyan Liu, Sheng Yang, Xiangru Zhang, Yuankai Shi
AIM: Apatinib, an oral tyrosine kinase inhibitor mainly targeting VEGFR-2, exerts both antiangiogenesis and antiproliferation effects. Apatinib shows clinical benefit in advanced non-small cell lung cancer (NSCLC) at an initial dose of 750 mg qd. We further assessed the efficacy and safety of apatinib at a more frequently used dose of 500 mg qd. The preliminary clinical outcome of apatinib in patients with brain metastases was also reported. METHODS: We retrospectively reviewed the clinical data of 25 patients who received apatinib between August 2015 and May 2016...
December 15, 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29243171/ipscs-based-generation-of-vascular-cells-reprogramming-approaches-and-applications
#13
REVIEW
Diana Klein
Recent advances in the field of induced pluripotent stem cells (iPSCs) research have opened a new avenue for stem cell-based generation of vascular cells. Based on their growth and differentiation potential, human iPSCs constitute a well-characterized, generally unlimited cell source for the mass generation of lineage- and patient-specific vascular cells without any ethical concerns. Human iPSCs-derived vascular cells are perfectly suited for vascular disease modeling studies because patient-derived iPSCs possess the disease-causing mutation, which might be decisive for full expression of the disease phenotype...
December 14, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29242990/the-influence-of-cochlear-morphology-on-the-final-electrode-array-position
#14
M C Ketterer, A Aschendorff, S Arndt, F Hassepass, T Wesarg, R Laszig, R Beck
OBJECTIVE: Preoperative information about cochlear morphology and size increasingly seems to be a defining factor of electrode choice in cochlear implant surgery. Different types of electrodes differ in length and diameter to accommodate individual cochlear anatomy. Smaller cochlear size results in increased insertion depth with a higher risk to dislocate and causes cochlear trauma with reduced postoperative outcome. The objective of the current study is to describe the three-dimensional size of the cochlea, to compare interindividual differences, to determine the relationship between cochlear size and insertion angle, and to define risk factors for dislocation during insertion...
December 14, 2017: European Archives of Oto-rhino-laryngology
https://www.readbyqxmd.com/read/29242981/a%C3%A2-new-look-at-the-heart-novel-imaging-techniques
#15
REVIEW
C M Johnston, A J Krafft, M F Russe, E A Rog-Zielinska
The development and successful implementation of cutting-edge imaging technologies to visualise cardiac anatomy and function is a key component of effective diagnostic efforts in cardiology. Here, we describe a number of recent exciting advances in the field of cardiology spanning from macro- to micro- to nano-scales of observation, including magnetic resonance imaging, computed tomography, optical mapping, photoacoustic imaging, and electron tomography. The methodologies discussed are currently making the transition from scientific research to routine clinical use, albeit at different paces...
December 14, 2017: Herzschrittmachertherapie & Elektrophysiologie
https://www.readbyqxmd.com/read/29242834/novel-its1-fungal-primers-for-characterization-of-the-mycobiome
#16
Mykhaylo Usyk, Christine P Zolnik, Hitesh Patel, Michael H Levi, Robert D Burk
Studies of the human microbiome frequently omit characterization of fungal communities (the mycobiome), which limits our ability to investigate how fungal communities influence human health. The internal transcribed spacer 1 (ITS1) region of the eukaryotic ribosomal cluster has features allowing for wide taxonomic coverage and has been recognized as a suitable barcode region for species-level identification of fungal organisms. We developed custom ITS1 primer sets using iterative alignment refinement. Primer performance was evaluated using in silico testing and experimental testing of fungal cultures and human samples...
November 2017: MSphere
https://www.readbyqxmd.com/read/29242522/amyloid-%C3%AE-and-tau-complexity-towards-improved-biomarkers-and-targeted-therapies
#17
REVIEW
Juan Carlos Polanco, Chuanzhou Li, Liviu-Gabriel Bodea, Ramon Martinez-Marmol, Frederic A Meunier, Jürgen Götz
Most neurodegenerative diseases are proteinopathies, which are characterized by the aggregation of misfolded proteins. Although many proteins have an intrinsic propensity to aggregate, particularly when cellular clearance systems start to fail in the context of ageing, only a few form fibrillar aggregates. In Alzheimer disease, the peptide amyloid-β (Aβ) and the protein tau aggregate to form plaques and tangles, respectively, which comprise the histopathological hallmarks of this disease. This Review discusses the complexity of Aβ biogenesis, trafficking, post-translational modifications and aggregation states...
December 15, 2017: Nature Reviews. Neurology
https://www.readbyqxmd.com/read/29242391/method-verification-requirements-for-an-advanced-imaging-system-for-microbial-plate-count-enumeration
#18
David Jones, Tony Cundell
Technical Abstract: The Growth Direct™ System that automates the incubation and reading of membrane filtration microbial counts on soybean-casein digest, Sabouraud dextrose and R2A agar differs only from the traditional method in that micro-colonies on the membrane are counted using an advanced imaging system up to 50% earlier in the incubation. Based on the recommendations in USP <1223> Validation of New Microbiological Testing Methods, the system may be implemented in a microbiology laboratory after simple method verification and not a full method validation...
December 14, 2017: PDA Journal of Pharmaceutical Science and Technology
https://www.readbyqxmd.com/read/29242381/therapeutic-targeting-of-non-coding-rnas-in-cancer
#19
REVIEW
Ondrej Slaby, Richard Laga, Ondrej Sedlacek
The majority of the human genome encodes RNAs that do not code for proteins. These non-coding RNAs (ncRNAs) affect normal expression of the genes, including oncogenes and tumour suppressive genes, which make them a new class of targets for drug development in cancer. Although microRNAs (miRNAs) are the most studied regulatory ncRNAs to date, and miRNA-targeted therapeutics have already reached clinical development, including the mimics of the tumour suppressive miRNAs miR-34 and miR-16, which reached phase I clinical trials for the treatment of liver cancer and mesothelioma, the importance of long non-coding RNAs (lncRNAs) is increasingly being recognised...
December 14, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29242344/activation-of-surface-lattice-oxygen-in-single-atom-pt-ceo2-for-low-temperature-co-oxidation
#20
Lei Nie, Donghai Mei, Haifeng Xiong, Bo Peng, Zhibo Ren, Xavier Isidro Pereira Hernandez, Andrew DeLaRiva, Meng Wang, Mark H Engelhard, Libor Kovarik, Abhaya K Datye, Yong Wang
To improve fuel efficiency, advanced combustion engines are being designed to minimize the amount of heat wasted in the exhaust. Hence, future generations of catalysts must perform at temperatures that are 100°C lower than current exhaust-treatment catalysts. Achieving low-temperature activity, while surviving the harsh conditions encountered at high engine loads, remains a formidable challenge. In this study, we demonstrate how atomically dispersed ionic platinum (Pt2+) on ceria (CeO2), which is already thermally stable, can be activated via steam treatment (at 750°C) to simultaneously achieve the goals of low-temperature carbon monoxide (CO) oxidation activity while providing outstanding hydrothermal stability...
December 15, 2017: Science
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