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https://www.readbyqxmd.com/read/29317452/autophagy-sustains-pancreatic-cancer-growth-through-both-cell-autonomous-and-non-autonomous-mechanisms
#1
Annan Yang, Grit Herter-Sprie, Haikuo Zhang, Elaine Y Lin, Douglas Biancur, Xiaoxu Wang, Jiehui Deng, Josephine Hai, Shenghong Yang, Kwok-Kin Wong, Alec C Kimmelman
Autophagy has been shown to be elevated in pancreatic adenocarcinoma (PDAC) and its role in promoting established tumor growth has made it a promising therapeutic target. However, due to limitations of prior mouse models as well as the lack of potent and selective autophagy inhibitors, the ability to fully assess the mechanistic basis of how autophagy supports pancreatic cancer has been limited. To test the feasibility of treating PDAC using autophagy inhibition and further our understanding of the mechanisms of pro-tumor effects of autophagy, we developed a novel mouse model that allowed the acute and reversible inhibition of autophagy...
January 9, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29300472/surface-modified-wooden-tip-electrospray-ionization-mass-spectrometry-for-enhanced-detection-of-analytes-in-complex-samples
#2
Bin Hu, Pui-Kin So, Yunyun Yang, Jiewei Deng, Yi-Ching Choi, Tiangang Luan, Zhong-Ping Yao
Replacement of capillary with solid substrates for sample loading and ionization has created many new possibilities for electrospray ionization mass spectrometry (ESI-MS). Surface modification is an attractive strategy to enhance the analytical capability of solid-substrate ESI-MS and allow understanding the relationship between surface activity of solid substrates and analytical properties. In this study, we performed surface modification of wooden tips with hydrophobic (-C18), basic (-NH2) and acidic (-SO3H) functional groups and applied various sampling methods, i...
January 4, 2018: Analytical Chemistry
https://www.readbyqxmd.com/read/29295932/noncanonical-agonist-ppar%C3%AE-ligands-modulate-the-response-to-dna-damage-and-sensitize-cancer-cells-to-cytotoxic-chemotherapy
#3
Melin J Khandekar, Alexander S Banks, Dina Laznik-Bogoslavski, James P White, Jang Hyun Choi, Lawrence Kazak, James C Lo, Paul Cohen, Kwok-Kin Wong, Theodore M Kamenecka, Patrick R Griffin, Bruce M Spiegelman
The peroxisome-proliferator receptor-γ (PPARγ) is expressed in multiple cancer types. Recently, our group has shown that PPARγ is phosphorylated on serine 273 (S273), which selectively modulates the transcriptional program controlled by this protein. PPARγ ligands, including thiazolidinediones (TZDs), block S273 phosphorylation. This activity is chemically separable from the canonical activation of the receptor by agonist ligands and, importantly, these noncanonical agonist ligands do not cause some of the known side effects of TZDs...
January 2, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29289605/spatial-patterns-generated-by-simultaneous-cooperation-and-exploitation-favour-the-evolution-of-altruism
#4
Atsushi Yamauchi, Minus van Baalen, Maurice Sabelis
In kin selection theory in the evolution of social behaviours, the relatedness between interacting individuals is influenced by the spatial structure of the population. It is generally considered that in the 'viscous' population competition among individuals tends to suppress the evolution of altruism. We consider that more complex interactions produce specific spatial patterns in the presence of competitive interaction, which could alter the process of kin selection in a given space. Here, we theoretically studied the joint evolution of altruism and resource exploitation in a spatially structured population...
December 28, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29281983/resource-competition-promotes-tumour-expansion-in-experimentally-evolved-cancer
#5
Tiffany B Taylor, Anastasia V Wass, Louise J Johnson, Phil Dash
BACKGROUND: Tumour progression involves a series of phenotypic changes to cancer cells, each of which presents therapeutic targets. Here, using techniques adapted from microbial experimental evolution, we investigate the evolution of tumour spreading - a precursor for metastasis and tissue invasion - in environments with varied resource supply. Evolutionary theory predicts that competition for resources within a population will select for individuals to move away from a natal site (i...
December 27, 2017: BMC Evolutionary Biology
https://www.readbyqxmd.com/read/29276047/overcoming-resistance-to-the-thz-series-of-covalent-transcriptional-cdk-inhibitors
#6
Yang Gao, Tinghu Zhang, Hideki Terai, Scott B Ficarro, Nicholas Kwiatkowski, Ming-Feng Hao, Bandana Sharma, Camilla L Christensen, Edmond Chipumuro, Kwok-Kin Wong, Jarrod A Marto, Peter S Hammerman, Nathanael S Gray, Rani E George
Irreversible inhibition of transcriptional cyclin-dependent kinases (CDKs) provides a therapeutic strategy for cancers that rely on aberrant transcription; however, lack of understanding of resistance mechanisms to these agents will likely impede their clinical evolution. Here, we demonstrate upregulation of multidrug transporters ABCB1 and ABCG2 as a major mode of resistance to THZ1, a covalent inhibitor of CDKs 7, 12, and 13 in neuroblastoma and lung cancer. To counter this obstacle, we developed a CDK inhibitor, E9, that is not a substrate for ABC transporters, and by selecting for resistance, determined that it exerts its cytotoxic effects through covalent modification of cysteine 1039 of CDK12...
December 15, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29259240/persistent-social-isolation-reflects-identity-and-social-context-but-not-maternal-effects-or-early-environment
#7
L J N Brent, A Ruiz-Lambides, M L Platt
Individuals who are well integrated into society have greater access to resources and tend to live longer. Why some individuals are socially isolated and others are not is therefore puzzling from an evolutionary perspective. Answering this question requires establishing the mix of intrinsic and contextual factors that contribute to social isolation. Using social network data spanning up to half of the median adult lifespan in a gregarious primate, we found that some measures of social isolation were modestly repeatable within individuals, consistent with a trait...
December 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29244566/the-price-equation-gradient-dynamics-and-continuous-trait-game-theory
#8
Jussi Lehtonen
A recent article convincingly nominated the Price equation as the fundamental theorem of evolution and used it as a foundation to derive several other theorems. A major section of evolutionary theory that was not addressed is that of game theory and gradient dynamics of continuous traits with frequency-dependent fitness. Deriving fundamental results in these fields under the unifying framework of the Price equation illuminates similarities and differences between approaches and allows a simple, unified view of game-theoretical and dynamic concepts...
January 2018: American Naturalist
https://www.readbyqxmd.com/read/29238696/identification-of-clinically-approved-drugs-indacaterol-and-canagliflozin-for-repurposing-to-treat-epidermal-growth-factor-tyrosine-kinase-inhibitor-resistant-lung-cancer
#9
Hongjian Li, Christy Wing-Sum Tong, Yee Leung, Man-Hon Wong, Kenneth Kin-Wah To, Kwong-Sak Leung
In advanced lung cancer, epidermal growth factor tyrosine kinase inhibitors (EGFR TKIs) have extraordinary clinical efficacy. However, their usefulness is severely compromised by drug resistance mediated by various mechanisms, the most important of which is the secondary EGFR T790M mutation. The mutation blocks the binding of EGFR TKIs to the receptor kinase, thereby abolishing the therapeutic efficacy. In this study, we used our free and open-source protein-ligand docking software idock to screen worldwide approved small-molecule drugs against EGFR T790M...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29234885/the-influence-of-related-and-unrelated-co-infections-on-parasite-dynamics-and-virulence
#10
A M Gleichsner, K Reinhart, D J Minchella
Many parasitic infections increase the morbidity and mortality of host populations. Interactions between co-infecting parasites can influence virulence, the damage done to a host. Previous studies investigating the impacts of parasite co-infection on hosts have been limited by their inability to control parasite dosage, use consistent virulence metrics, or verify co-infection status. This study used molecular tools, known infection dosage, and multiple assessments over time to test whether parasite relatedness can predict virulence in co-infections, as well as whether competitive interactions between different parasite strains within a host are predictable over time...
December 12, 2017: Oecologia
https://www.readbyqxmd.com/read/29230029/publisher-correction-social-polymorphism-is-favoured-by-the-co-evolution-of-dispersal-with-social-behaviour
#11
Charles Mullon, Laurent Keller, Laurent Lehmann
Owing to a technical error, some text was missing in the originally published version of this Article. In the last paragraph of the Discussion section, the second sentence should have read "Yet, the selection that associates dispersal and social behaviour in our model will influence evolution under most ecological settings because it depends only on kin structure, which, due to limited dispersal and the spatial scale of social interactions, is ubiquitous in nature47." This error has now been corrected in all versions of the Article...
December 11, 2017: Nature Ecology & Evolution
https://www.readbyqxmd.com/read/29225285/evaluation-of-probiotic-and-prebiotic-like-effects-of-bacillus-subtilis-bn-on-growth-of-lactobacilli
#12
Masanori Horie, Taisuke Koike, Sakiko Sugino, Aya Umeno, Yasukazu Yoshida
The aim of this study was to determine the probiotic and the prebiotic-like properties of Bacillus subtilis BN, a spore-forming bacterium, also known as "natto-kin", which is used for making the Japanese fermented food, natto. We used the spores and vegetative cells of this strain and compared their effects on the growth of lactobacilli. Culture supernatant from B. subtilis BN was added to a glucose-free MRS medium used to culture lactobacilli. When lactobacilli were cultured in the supernatant-containing medium, growth was improved...
December 8, 2017: Journal of General and Applied Microbiology
https://www.readbyqxmd.com/read/29216547/seasonal-variations-of-c1-c4-alkyl-nitrates-at-a-coastal-site-in-hong-kong-influence-of-photochemical-formation-and-oceanic-emissions
#13
Junwei Song, Yingyi Zhang, Yu Huang, Kin Fai Ho, Zibing Yuan, Zhenhao Ling, Xiaojun Niu, Yuan Gao, Long Cui, Peter K K Louie, Shun-Cheng Lee, Senchao Lai
Five C1-C4 alkyl nitrates (RONO2) were measured at a coastal site in Hong Kong in four selected months of 2011 and 2012. The total mixing ratios of C1-C4 RONO2 (Σ5RONO2) ranged from 15.4 to 143.7 pptv with an average of 65.9 ± 33.0 pptv. C3-C4 RONO2 (2-butyl nitrate and 2-propyl nitrate) were the most abundant RONO2 during the entire sampling period. The mixing ratios of C3-C4 RONO2 were higher in winter than those in summer, while the ones of methyl nitrate (MeONO2) were higher in summer than those in winter...
November 21, 2017: Chemosphere
https://www.readbyqxmd.com/read/29206171/kin-selection-in-the-rna-world
#14
Samuel R Levin, Stuart A West
Various steps in the RNA world required cooperation. Why did life's first inhabitants, from polymerases to synthetases, cooperate? We develop kin selection models of the RNA world to answer these questions. We develop a very simple model of RNA cooperation and then elaborate it to model three relevant issues in RNA biology: (1) whether cooperative RNAs receive the benefits of cooperation; (2) the scale of competition in RNA populations; and (3) explicit replicator diffusion and survival. We show: (1) that RNAs are likely to express partial cooperation; (2) that RNAs will need mechanisms for overcoming local competition; and (3) in a specific example of RNA cooperation, persistence after replication and offspring diffusion allow for cooperation to overcome competition...
December 5, 2017: Life
https://www.readbyqxmd.com/read/29195838/a-phenomenological-analysis-of-eco-evolutionary-coupling-under-dilution
#15
Vitor H Sanches, Dhyan V H Kuraoka, Pedro R Almeida, Carla Goldman
Evolutionary dynamics experienced by mixed microbial populations of cooperators and cheaters has been examined in experiments in the literature using a protocol of periodic dilution to investigate the properties of resilience and adaptability to environmental changes. Data depicted on an appropriate phase diagram indicate, among other features, a stable equilibrium point at which cooperators and cheaters coexist (Sanchez A, Gore J. Feedback between population and evolutionary dynamics determines the fate of social microbial populations...
November 28, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29166167/kinship-and-incest-avoidance-drive-patterns-of-reproductive-skew-in-cooperatively-breeding-birds
#16
Christina Riehl
Social animals vary in how reproduction is divided among group members, ranging from monopolization by a dominant pair (high skew) to equal sharing by cobreeders (low skew). Despite many theoretical models, the ecological and life-history factors that generate this variation are still debated. Here I analyze data from 83 species of cooperatively breeding birds, finding that kinship within the breeding group is a powerful predictor of reproductive sharing across species. Societies composed of nuclear families have significantly higher skew than those that contain unrelated members, a pattern that holds for both multimale and multifemale groups...
December 2017: American Naturalist
https://www.readbyqxmd.com/read/29156907/the-palliative-care-needs-for-those-advanced-neurology-patients-on-mechanical-ventilator-support
#17
Tsz Kin Kwok
There are mainly two types of needs for the ventilator users with severe neurological diseases: respiratory related needs include mode of ventilation selection, mode of ventilator prescription, maintaining lung recruitment and good airway clearance; non-respiratory related needs include substantial nursing care, adequate nutrition, accessible communication and psychological support. All these are important to maintain the quality of life of these patients.
September 13, 2017: Annals of Palliative Medicine
https://www.readbyqxmd.com/read/29109264/epoxide-metabolites-of-arachidonate-and-docosahexaenoate-function-conversely-in-acute-kidney-injury-involved-in-gsk3%C3%AE-signaling
#18
Bing-Qing Deng, Ying Luo, Xin Kang, Chang-Bin Li, Christophe Morisseau, Jun Yang, Kin Sing Stephen Lee, Jian Huang, Da-Yong Hu, Ming-Yu Wu, Ai Peng, Bruce D Hammock, Jun-Yan Liu
Acute kidney injury (AKI) causes severe morbidity and mortality for which new therapeutic strategies are needed. Docosahexaenoic acid (DHA), arachidonic acid (ARA), and their metabolites have various effects in kidney injury, but their molecular mechanisms are largely unknown. Here, we report that 14 (15)-epoxyeicosatrienoic acid [14 (15)-EET] and 19 (20)-epoxydocosapentaenoic acid [19 (20)-EDP], the major epoxide metabolites of ARA and DHA, respectively, have contradictory effects on kidney injury in a murine model of ischemia/reperfusion (I/R)-caused AKI...
November 21, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29104298/interference-in-early-dual-task-learning-by-predatory-mites
#19
Inga C Christiansen, Peter Schausberger
Animals are commonly exposed to multiple environmental stimuli, but whether, and under which circumstances, they can attend to multiple stimuli in multitask learning challenges is elusive. Here, we assessed whether simultaneously occurring chemosensory stimuli interfere with each other in a dual-task learning challenge. We exposed predatory mites Neoseiulus californicus early in life to either only conspecifics (kin) or simultaneously conspecifics (kin) and food (thrips or pollen), to determine whether presence of food interferes with social familiarization and, vice versa, whether presence of conspecifics interferes with learning the cues of thrips...
November 2017: Animal Behaviour
https://www.readbyqxmd.com/read/29080969/altruistic-behavior-among-twins-willingness-to-fight-and-self-sacrifice-for-their-closest-relatives
#20
Encarnación Tornero, Juan F Sánchez-Romera, José J Morosoli, Alexandra Vázquez, Ángel Gómez, Juan R Ordoñana
According to kin selection theory, indirect reproductive advantages may induce individuals to care for others with whom they share genes by common descent, and the amount of care, including self-sacrifice, will increase with the proportion of genes shared. Twins represent a natural situation in which this hypothesis can be tested. Twin pairs experience the same early environment because they were born and raised at the same time and in the same family but their genetic relatedness differs depending on zygosity...
October 28, 2017: Human Nature: An Interdisciplinary Biosocial Perspective
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