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https://www.readbyqxmd.com/read/29454281/probing-the-%C3%AE-pocket-of-the-active-site-of-human-liver-glycogen-phosphorylase-with-3-c-%C3%AE-d-glucopyranosyl-5-4-substituted-phenyl-1-2-4-triazole-inhibitors
#1
Efthimios Kyriakis, Theodora G A Solovou, Sándor Kun, Katalin Czifrák, Béla Szőcs, László Juhász, Éva Bokor, George A Stravodimos, Anastassia L Kantsadi, Demetra S M Chatzileontiadou, Vassiliki T Skamnaki, László Somsák, Demetres D Leonidas
Human liver glycogen phosphorylase (hlGP), a key enzyme in glycogen metabolism, is a valid pharmaceutical target for the development of new anti-hyperglycaemic agents for type 2 diabetes. Inhibitor discovery studies have focused on the active site and in particular on glucopyranose based compounds with a β-1 substituent long enough to exploit interactions with a cavity adjacent to the active site, termed the β-pocket. Recently, C-β-d-glucopyranosyl imidazoles and 1, 2, 4-triazoles proved to be the best known glucose derived inhibitors of hlGP...
February 12, 2018: Bioorganic Chemistry
https://www.readbyqxmd.com/read/29454272/dealing-with-the-nucleus-during-cell-migration
#2
REVIEW
Francisco J Calero-Cuenca, Cátia S Janota, Edgar R Gomes
The position of the nucleus within cells is a key event during cell migration. The movement and positioning of the nucleus strongly impacts cell migration. Notably, the last two years largely contributed to emphasise the dynamicity of the nucleus-cytoskeleton interactions that occur during cell migration. Nuclei are under continuous tension from opposing intracellular forces and its tether to the cytoskeleton can be regulated at different levels. Interestingly, it was showed how nuclear positioning is highly related to cell function...
February 14, 2018: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29454183/the-fine-balance-between-mutualism-and-antagonism-in-the-epichlo%C3%A3-festucae-grass-symbiotic-interaction
#3
REVIEW
Barry Scott, Kimberly Green, Daniel Berry
Epichloë endophytes form mutualistic symbiotic associations with aerial tissues of temperate grasses. Intercalary growth of hyphae within the leaves enables fungal growth to be synchronized with host leaf growth, leading to formation of a highly structured and tightly regulated symbiotic network. Mutations in fungal genes that disrupt cell-cell fusion and other key signalling pathways lead to an antagonistic interaction characterized by unregulated growth of endophytic hyphae and detrimental effects on host growth...
February 14, 2018: Current Opinion in Plant Biology
https://www.readbyqxmd.com/read/29454079/a-novel-metric-that-quantifies-risk-stratification-for-evaluating-diagnostic-tests-the-example-of-evaluating-cervical-cancer-screening-tests-across-populations
#4
Hormuzd A Katki, Mark Schiffman
Our work involves assessing whether new biomarkers might be useful for cervical-cancer screening across populations with different disease prevalences and biomarker distributions. When comparing across populations, we show that standard diagnostic accuracy statistics (predictive values, risk-differences, Youden's index and Area Under the Curve (AUC)) can easily be misinterpreted. We introduce an intuitively simple statistic for a 2 × 2 table, Mean Risk Stratification (MRS): the average change in risk (pre-test vs...
February 14, 2018: Preventive Medicine
https://www.readbyqxmd.com/read/29454068/o-glcnacylation-of-rack1-promotes-hepatocellular-carcinogenesis
#5
Fangfang Duan, Hao Wu, Dongwei Jia, Weicheng Wu, Shifang Ren, Lan Wang, Shushu Song, Xinying Guo, Fenglin Liu, Yuanyuan Ruan, Jianxin Gu
BACKGROUND & AIMS: Aberrant oncogenic mRNA translation and protein O-linked β-N-acetylglucosaminylation (O-GlcNAcylation) are general features during tumorigenesis. Nevertheless, whether and how these two pathways are interlinked remain unknown. Our previous study indicated that ribosomal RACK1 promoted the chemoresistance and growth in hepatocellular carcinoma (HCC). The aim of this study is to examine the role of RACK1 O-GlcNAcylation in oncogene translation and HCC carcinogenesis...
February 14, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29454038/dendritic-cells-as-cancer-therapeutics
#6
REVIEW
Christian E Bryant, Sarah Sutherland, Benjamin Kong, Michael S Papadimitrious, Derek N J Hart
The ability of immune therapies to control cancer has recently generated intense interest. This therapeutic outcome is reliant on T cell recognition of tumour cells. The natural function of dendritic cells (DC) is to generate adaptive responses, by presenting antigen to T cells, hence they are a logical target to generate specific anti-tumour immunity. Our understanding of the biology of DC is expanding, and they are now known to be a family of related subsets with variable features and function. Most clinical experience to date with DC vaccination has been using monocyte-derived DC vaccines...
February 14, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29453986/sterol-o-acyltransferase-1-deficiency-improves-defective-insulin-signaling-in-the-brains-of-mice-fed-a-high-fat-diet
#7
Ning Xu, Hao Meng, Tian-Yi Liu, Ying-Li Feng, Yuan Qi, Dong-Huan Zhang, Hong-Lei Wang
Insulin resistance induced by a high-fat diet (HFD) is related to metabolic diseases, and sterol O-acyltransferase 1 (SOAT1) is a key enzyme for the biosynthesis of cholesteryl ester. In the present study, wild-type (WT) mice and SOAT1-knockout (KO) mice with a C57BL6 background fed a HFD were used to explore the role of SOAT1 in the hypothalamus. The results show that the WT mice exhibited a significant increase in body weight as well as hepatic histologic changes; they also had a lower glucose and insulin tolerance than the WT mice fed a normal diet...
February 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29453982/glucagon-like-peptide-1-contributes-to-increases-abca1-expression-by-downregulating-mir-758-to-regulate-cholesterol-homeostasis
#8
Yue Yao, Qiang Li, Ping Gao, Wei Wang, Lili Chen, Jinchao Zhang, Yi Xu
Abnormal regulation of lipid metabolism is associated with type 2 diabetes mellitus (T2DM). GLP-1 as a new treatment for T2DM, has unique effects in modulating cholesterol homeostasis. However, the mechanism of this effect is largely missing. The aim of this study was to determine the effects of GLP-1 on cholesterol-induced lipotoxicity in hepatocytes and examine the underlying mechanisms. The cell viability was determined, and caspase-3 was used to detect the effects of GLP-1 on cholesterol-induced apoptosis...
February 14, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29453960/synaptic-dysfunction-and-altered-excitability-in-c9orf72-als-ftd
#9
Alexander Starr, Rita Sattler
Amyotrophic lateral sclerosis (ALS) is characterized by a progressive degeneration of upper and lower motor neurons, resulting in fatal paralysis due to denervation of the muscle. Due to genetic, pathological and symptomatic overlap, ALS is now considered a spectrum disease together with frontotemporal dementia (FTD), the second most common cause of dementia in individuals under the age of 65. Interestingly, in both diseases, there is a large prevalence of RNA binding proteins (RBPs) that are mutated and considered disease-causing, or whose dysfunction contribute to disease pathogenesis...
February 14, 2018: Brain Research
https://www.readbyqxmd.com/read/29453950/towards-elimination-of-schistosomiasis-after-5000-years-of-endemicity-in-egypt
#10
REVIEW
Iman F Abou-El-Naga
Schistosomiasis is a snail-transmitted infectious disease caused by a long lasting infection with a blood fluke of the genus Schistosoma. S. haematobium and S. mansoni are the species endemic in Egypt. The country has been plagued and seriously suffered from schistosomiasis over the past 5000 years. Great strides had been done in controlling the disease since 1922. The history, epidemiology and the different control approaches were reviewed. Currently, Egypt is preparing towards schistosomiasis elimination by 2020...
February 14, 2018: Acta Tropica
https://www.readbyqxmd.com/read/29453948/noncritical-signaling-role-of-a-kinase-receptor-interaction-surface-in-the-escherichia-coli-chemosensory-core-complex
#11
Germán E Piñas, Michael D DeSantis, John S Parkinson
In E. coli chemosensory arrays, transmembrane receptors, a histidine autokinase CheA, and a scaffolding protein CheW interact to form an extended hexagonal lattice of signaling complexes. One interaction, previously assigned a crucial signaling role, occurs between chemoreceptors and the CheW-binding P5 domain of CheA. Structural studies showed a receptor helix fitting into a hydrophobic cleft at the boundary between P5 subdomains. Our work aimed to elucidate the in vivo roles of the receptor-P5 interface, employing as a model the interaction between E...
February 14, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29453930/ensemble-survival-tree-models-to-reveal-pairwise-interactions-of-variables-with-time-to-events-outcomes-in-low-dimensional-setting
#12
Jean-Eudes Dazard, Hemant Ishwaran, Rajeev Mehlotra, Aaron Weinberg, Peter Zimmerman
Unraveling interactions among variables such as genetic, clinical, demographic and environmental factors is essential to understand the development of common and complex diseases. To increase the power to detect such variables interactions associated with clinical time-to-events outcomes, we borrowed established concepts from random survival forest (RSF) models. We introduce a novel RSF-based pairwise interaction estimator and derive a randomization method with bootstrap confidence intervals for inferring interaction significance...
February 17, 2018: Statistical Applications in Genetics and Molecular Biology
https://www.readbyqxmd.com/read/29453928/cd4-cd25-cd127low-foxp3-regulatory-t-cells-in-crohn-s-disease
#13
Ali Khalili, Soheil Ebrahimpour, Iradj Maleki, Saeid Abediankenari, Mousa Mohammadnia Afrouzi
BACKGROUND: Regulatory T (Treg) cell play a key role in autoimmune diseases. We evaluated the regulatory function and frequency of Treg cells and secreted IL-10, IL-35 concentration in Crohn's disease (CD). METHODS: Twenty-three patients with CD and 25 healthy controls (HC) were included in this study. We analysed the alteration of Tregs frequency using flow cytometry for CD4, CD25, CD127 and FoxP3 markers. Surface expression of CD4, CD25 and CD127 markers were used for isolation of a relatively pure Treg cells...
February 16, 2018: Romanian Journal of Internal Medicine, Revue Roumaine de Médecine Interne
https://www.readbyqxmd.com/read/29453864/-lpcat1-controls-phosphate-homeostasis-in-a-zinc-dependent-manner
#14
Mushtak Kisko, Nadia Bouain, Alaeddine Safi, Anna Medici, Robert C Akkers, David Secco, Gilles Fouret, Gabriel Krouk, Mark Gm Aarts, Wolfgang Busch, Hatem Rouached
All living organisms require a variety of essential elements for their basic biological functions. While the homeostasis of nutrients is highly intertwined, the molecular and genetic mechanisms of these dependencies remains poorly understood. Here, we report a discovery of a molecular pathway that control phosphate (Pi) accumulation plants in Zn deficiency. Using genome-wide association studies we first identified allelic variation of the Lyso-PhosphatidylCholine (PC) AcylTransferase 1 ( LPCAT1 ) gene as the key determinant of shoot Pi accumulation under Zn deficiency...
February 17, 2018: ELife
https://www.readbyqxmd.com/read/29453862/insights-into-transcriptional-silencing-and-anti-silencing-in-shigella-flexneri-a-detailed-molecular-analysis-of-the-icsp-virulence-locus
#15
Natasha Weatherspoon-Griffin, Michael A Picker, Krystle L Pew, Hiromichi S Park, Daren Ginete, Monika M Karney, Pashtana Usufzy, Maria I Castellanos, Juan Carlos Duhart, Dustin J Harrison, Jillian N Socea, Alexander D Karabachev, Christopher T Hensley, Amber J Howerton, Rosa Ojeda-Daulo, Joy A Immak, Helen J Wing
Transcriptional silencing and anti-silencing mechanisms modulate bacterial physiology and virulence in many human pathogens. In Shigella species, many virulence plasmid genes are silenced by the histone-like nucleoid structuring protein H-NS and anti-silenced by the virulence gene regulator VirB. Despite the key role that these regulatory proteins play in Shigella virulence, their mechanisms of transcriptional control remain poorly understood. Here, we characterize the regulatory elements and their relative spacing requirements needed for the transcriptional silencing and anti-silencing of icsP, a locus that requires remotely located regulatory elements for both types of transcriptional control...
February 17, 2018: Molecular Microbiology
https://www.readbyqxmd.com/read/29453861/virus-like-particle-engineering-from-rational-design-to-versatile-applications
#16
REVIEW
Xuanwei Ding, Dong Liu, George Booth, Wei Gao, Yuan Lu
As mimicking natural virus structures, virus-like particles (VLPs) have evolved to become a widely accepted technology used for humans which are safe, highly efficacious and profitable. Several remarkable advantages have been achieved to revolutionize the molecule delivery for diverse applications in nanotechnology, biotechnology, and medicine. Here, we review the rational structure design, manufacturing process, functionalization strategy, and emerging applications of VLPs. The situation and challenges in the VLP engineering, the key development orientation, and future applications have been discussed...
February 17, 2018: Biotechnology Journal
https://www.readbyqxmd.com/read/29453844/integrating-scenario-planning-and-cost-benefit-methods
#17
Stephen C Aldrich
By their nature, the most vexing social problems reflect collisions between social and economic interests of parties with highly divergent views and perspectives on the cause and character of what is at issue and the consequences that flow from it. Conflicts around biotechnology applications are good examples of these problems. When considering the potential consequences of proposed biotechnology applications, an enormous range of perspectives arise reflecting the breadth of different and often competing interests with a stake in life's future...
January 2018: Hastings Center Report
https://www.readbyqxmd.com/read/29453807/tunable-poly-methacrylic-acid-co-acrylamide-nanoparticles-through-inverse-emulsion-polymerization
#18
Justin X Zhong, John R Clegg, Eric W Ander, Nicholas A Peppas
Environmentally responsive biomaterials have played key roles in the design of biosensors and drug delivery vehicles. Their physical response to external stimuli, such as temperature or pH, can transduce a signal or trigger the release of a drug. In this work, we designed a robust, highly tunable, pH responsive nanoscale hydrogel system. We present the design and characterization of poly((methacrylic acid) - co - acrylamide) hydrogel nanoparticles, crosslinked with methylenebisacrylamide, through inverse emulsion polymerization...
February 17, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29453803/competition-for-nutrients-and-light-testing-advances-in-resource-competition-with-a-natural-phytoplankton-community
#19
Amanda Burson, Maayke Stomp, Emma Greenwell, Julia Grosse, Jef Huisman
A key challenge in ecology is to understand how nutrients and light affect the biodiversity and community structure of phytoplankton and plant communities. According to resource competition models, ratios of limiting nutrients are major determinants of the species composition. At high nutrient levels, however, species interactions may shift to competition for light, which might make nutrient ratios less relevant. The "nutrient-load hypothesis" merges these two perspectives, by extending the classic model of competition for two nutrients to include competition for light...
February 17, 2018: Ecology
https://www.readbyqxmd.com/read/29453790/amyloid-beta-1-40-is-associated-with-alterations-in-ng2-pericyte-population-ex-vivo-and-in-vitro
#20
Nina Schultz, Kristoffer Brännström, Elin Byman, Simon Moussaud, Henrietta M Nielsen, Anders Olofsson, Malin Wennström
The population of brain pericytes, a cell type important for vessel stability and blood brain barrier function, has recently been shown altered in patients with Alzheimer's disease (AD). The underlying reason for this alteration is not fully understood, but progressive accumulation of the AD characteristic peptide amyloid-beta (Aβ) has been suggested as a potential culprit. In the current study, we show reduced number of hippocampal NG2+ pericytes and an association between NG2+ pericyte numbers and Aβ1-40 levels in AD patients...
February 17, 2018: Aging Cell
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