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adaptive pathways

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https://www.readbyqxmd.com/read/29232113/hyperbranched-polyglycerol-loaded-with-zinc-porphyrins-photosensitizer-release-under-reductive-and-acidic-conditions-for-improved-photodynamic-therapy
#1
Michael H Staegemann, Susanna Gräfe, Burkhard Gitter, Katharina Achazi, Elisa Quaas, Rainer Haag, Arno Wiehe
An adaptable approach toward cleavable nanoparticle carrier systems for photodynamic therapy (PDT) is presented, comprising a biocompatible carrier loaded with multiple photosensitizer (PS) molecules related to the clinically employed PS Temoporfin, two linkers cleavable under different triggers and glyco-targeting with mannose. A synthetic pathway to stimuli responsive hyperbranched polyglycerol (hPG) porphyrin conjugates via the copper(I)-catalyzed 1,3-dipolar cycloaddition (CuAAC) or the strain-promoted alkyne-azide cycloaddition (SPAAC) has been developed...
December 12, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/29231906/simulation-of-cellular-energy-restriction-in-quiescence-eriq-a-theoretical-model-for-aging
#2
David Alfego, Andres Kriete
Cellular responses to energy stress involve activation of pro-survival signaling nodes, compensation in regulatory pathways and adaptations in organelle function. Specifically, energy restriction in quiescent cells (ERiQ) through energetic perturbations causes adaptive changes in response to reduced ATP, NAD+ and NADP levels in a regulatory network spanned by AKT, NF-κB, p53 and mTOR. Based on the experimental ERiQ platform, we have constructed a minimalistic theoretical model consisting of feedback motifs that enable investigation of stress-signaling pathways...
December 12, 2017: Biology
https://www.readbyqxmd.com/read/29230182/a-network-model-to-explore-the-effect-of-the-micro-environment-on-endothelial-cell-behavior-during-angiogenesis
#3
Nathan Weinstein, Luis Mendoza, Isidoro Gitler, Jaime Klapp
Angiogenesis is an important adaptation mechanism of the blood vessels to the changing requirements of the body during development, aging, and wound healing. Angiogenesis allows existing blood vessels to form new connections or to reabsorb existing ones. Blood vessels are composed of a layer of endothelial cells (ECs) covered by one or more layers of mural cells (smooth muscle cells or pericytes). We constructed a computational Boolean model of the molecular regulatory network involved in the control of angiogenesis...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29230027/genome-of-the-tasmanian-tiger-provides-insights-into-the-evolution-and-demography-of-an-extinct-marsupial-carnivore
#4
Charles Y Feigin, Axel H Newton, Liliya Doronina, Jürgen Schmitz, Christy A Hipsley, Kieren J Mitchell, Graham Gower, Bastien Llamas, Julien Soubrier, Thomas N Heider, Brandon R Menzies, Alan Cooper, Rachel J O'Neill, Andrew J Pask
The Tasmanian tiger or thylacine (Thylacinus cynocephalus) was the largest carnivorous Australian marsupial to survive into the modern era. Despite last sharing a common ancestor with the eutherian canids ~160 million years ago, their phenotypic resemblance is considered the most striking example of convergent evolution in mammals. The last known thylacine died in captivity in 1936 and many aspects of the evolutionary history of this unique marsupial apex predator remain unknown. Here we have sequenced the genome of a preserved thylacine pouch young specimen to clarify the phylogenetic position of the thylacine within the carnivorous marsupials, reconstruct its historical demography and examine the genetic basis of its convergence with canids...
December 11, 2017: Nature Ecology & Evolution
https://www.readbyqxmd.com/read/29230022/trained-innate-immunity-a-salient-factor-in-the-pathogenesis-of-neuroimmune-psychiatric-disorders
#5
A P Salam, A Borsini, P A Zunszain
Historically, only cells of the adaptive immune system have been considered capable of retaining memory for infectious challenges. Recently, however, cells of the innate immune system have been shown to be capable of displaying long-term functional memory following a single immunostimulatory challenge, leading to enhanced production of proinflammatory molecules upon other subsequent, and temporally distant, immunostimulatory challenges. This effect has been termed 'trained innate immunity', and is underwritten by stable epigenetic changes in immune and metabolic pathways...
December 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/29230015/a-perk-mir-211-axis-suppresses-circadian-regulators-and-protein-synthesis-to-promote-cancer-cell-survival
#6
Yiwen Bu, Akihiro Yoshida, Nilesh Chitnis, Brian J Altman, Feven Tameire, Amanda Oran, Victoria Gennaro, Kent E Armeson, Steven B McMahon, Gerald B Wertheim, Chi V Dang, Davide Ruggero, Constantinos Koumenis, Serge Y Fuchs, J Alan Diehl
The unfolded protein response (UPR) is a stress-activated signalling pathway that regulates cell proliferation, metabolism and survival. The circadian clock coordinates metabolism and signal transduction with light/dark cycles. We explore how UPR signalling interfaces with the circadian clock. UPR activation induces a 10 h phase shift in circadian oscillations through induction of miR-211, a PERK-inducible microRNA that transiently suppresses both Bmal1 and Clock, core circadian regulators. Molecular investigation reveals that miR-211 directly regulates Bmal1 and Clock via distinct mechanisms...
December 11, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/29230001/diacylglycerol-triggers-rim101-pathway-dependent-necrosis-in-yeast-a-model-for-lipotoxicity
#7
Patrick Rockenfeller, Martin Smolnig, Jutta Diessl, Mina Bashir, Vera Schmiedhofer, Oskar Knittelfelder, Julia Ring, Joakim Franz, Ines Foessl, Muhammad J Khan, René Rost, Wolfgang F Graier, Guido Kroemer, Andreas Zimmermann, Didac Carmona-Gutierrez, Tobias Eisenberg, Sabrina Büttner, Stephan J Sigrist, Ronald P Kühnlein, Sepp D Kohlwein, Campbell W Gourlay, Frank Madeo
The loss of lipid homeostasis can lead to lipid overload and is associated with a variety of disease states. However, little is known as to how the disruption of lipid regulation or lipid overload affects cell survival. In this study we investigated how excess diacylglycerol (DG), a cardinal metabolite suspected to mediate lipotoxicity, compromises the survival of yeast cells. We reveal that increased DG achieved by either genetic manipulation or pharmacological administration of 1,2-dioctanoyl-sn-glycerol (DOG) triggers necrotic cell death...
December 11, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29229676/teleost-specific-tlr19-localizes-to-endosome-recognizes-dsrna-recruits-trif-triggers-both-ifn-and-nf-%C3%AE%C2%BAb-pathways-and-protects-cells-from-grass-carp-reovirus-infection
#8
Jianfei Ji, Youliang Rao, Quanyuan Wan, Zhiwei Liao, Jianguo Su
TLRs are pivotal pattern recognition receptors in initiating innate immunity and triggering adaptive immunity. TLR pathways have been comprehensively investigated in mammals. However, the teleost-specific TLR19 pathway remains largely unknown. In this study, we identified TLR19 from grass carp (Ctenopharyngodon idella), and explored the ligand, adaptor, and signaling pathways. Pathogen-associated molecular pattern binding and luciferase activity assays indicate that TLR19 recognizes and responds to dsRNA analog (polyinosinic:polycytidylic acid)...
December 11, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29229549/what-do-primary-immunodeficiencies-tell-us-about-the-essentiality-redundancy-of-immune-responses
#9
REVIEW
Alain Fischer, Antonio Rausell
Advances in genomics and medicine have enabled the identification of (currently) 346 primary immunodeficiencies (PIDs) caused by mutations in 336 different genes. Most of these PIDs are monogenic conditions with Mendelian inheritance. Given this large number, it is possible to analyze the distribution of PIDs associated with infections and/or immunopathology according to the nature of the defect - even though this exercise can be challenging and arguable because of the pleiotropic nature of some gene products...
December 8, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/29229443/immune-functions-of-insect-%C3%AE-grps-and-their-potential-application
#10
Xiang-Jun Rao, Ming-Yue Zhan, Yue-Min Pan, Su Liu, Pei-Jin Yang, Li-Ling Yang, Xiao-Qiang Yu
Insects rely completely on the innate immune system to sense the foreign bodies and to mount the immune responses. Germ-line encoded pattern recognition receptors play crucial roles in recognizing pathogen-associated molecular patterns. Among them, β-1,3-glucan recognition proteins (βGRPs) and gram-negative bacteria-binding proteins (GNBPs) belong to the same pattern recognition receptor family, which can recognize β-1,3-glucans. Typical insect βGRPs are comprised of a tandem carbohydrate-binding module in the N-terminal and a glucanase-like domain in the C-terminal...
December 8, 2017: Developmental and Comparative Immunology
https://www.readbyqxmd.com/read/29228930/gene-expression-analysis-in-asthma-using-a-targeted-multiplex-array
#11
Christopher D Pascoe, Ma'en Obeidat, Bryna A Arsenault, Yunlong Nie, Stephanie Warner, Dorota Stefanowicz, Samuel J Wadsworth, Jeremy A Hirota, S Jasemine Yang, Delbert R Dorscheid, Chris Carlsten, Tillie L Hackett, Chun Y Seow, Peter D Paré
BACKGROUND: Gene expression changes in the structural cells of the airways are thought to play a role in the development of asthma and airway hyperresponsiveness. This includes changes to smooth muscle contractile machinery and epithelial barrier integrity genes. We used a targeted gene expression arrays to identify changes in the expression and co-expression of genes important in asthma pathology. METHODS: RNA was isolated from the airways of donor lungs from 12 patients with asthma (8 fatal) and 12 non-asthmatics controls and analyzed using a multiplexed, hypothesis-directed platform to detect differences in gene expression...
December 11, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/29228548/macrophage-depletion-through-colony-stimulating-factor-1-receptor-pathway-blockade-overcomes-adaptive-resistance-to-anti-vegf-therapy
#12
Yasmin A Lyons, Sunila Pradeep, Sherry Y Wu, Monika Haemmerle, Jean M Hansen, Michael J Wagner, Alejandro Villar-Prados, Archana S Nagaraja, Robert L Dood, Rebecca A Previs, Wei Hu, Yang Zhao, Duncan H Mak, Zhilan Xiao, Brenda D Melendez, Gregory A Lizee, Imelda Mercado-Uribe, Keith A Baggerly, Patrick Hwu, Jinsong Liu, Willem W Overwijk, Robert L Coleman, Anil K Sood
Anti-angiogenesis therapy has shown clinical benefit in patients with high-grade serous ovarian cancer (HGSC), but adaptive resistance rapidly emerges. Thus, approaches to overcome such resistance are needed. We developed the setting of adaptive resistance to anti-VEGF therapy, and performed a series of in vivo experiments in both immune competent and nude mouse models. Given the pro-angiogenic properties of tumor-associated macrophages (TAMs) and the dominant role of CSF1R in macrophage function, we added CSF1R inhibitors following emergence of adaptive resistance to anti-VEGF antibody...
November 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/29226490/a-water-processable-and-bioactive-multivalent-graphene-nanoink-for-highly-flexible-bioelectronic-films-and-nanofibers
#13
Chong Cheng, Jianguang Zhang, Shuang Li, Yi Xia, Chuanxiong Nie, Zhenqiang Shi, Jose Luis Cuellar-Camacho, Nan Ma, Rainer Haag
The capabilities of conductive nanomaterials to be produced in liquid form with well-defined chemical, physical, and biological properties are highly important for the construction of next-generation flexible bioelectronic devices. Although functional graphene nanomaterials can serve as attractive liquid nanoink platforms for the fabrication of bioelectronics, scalable synthesis of graphene nanoink with an integration of high colloidal stability, water processability, electrochemical activity, and especially bioactivity remains a major challenge...
December 11, 2017: Advanced Materials
https://www.readbyqxmd.com/read/29225600/hypoxic-stress-induced-tumor-and-immune-plasticity-suppression-and-impact-on-tumor-heterogeneity
#14
REVIEW
Stéphane Terry, Stéphanie Buart, Salem Chouaib
The microenvironment of a developing tumor is composed of proliferating cancer cells, blood vessels, stromal cells, infiltrating inflammatory cells, and a variety of associated tissue cells. The crosstalk between stromal cells and malignant cells within this environment crucially determines the fate of tumor progression, its hostility, and heterogeneity. It is widely accepted that hypoxic stresses occur in most solid tumors. Moreover, cancer cells found within hypoxic regions are presumed to represent the most aggressive and therapy-resistant fractions of the tumor...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29225355/evolutionary-conservation-and-functional-divergence-of-the-lfk-gene-family-play-important-roles-in-the-photoperiodic-flowering-pathway-of-land-plants
#15
Ling Lu, Yuanqi Wu, Zhengqiao Liao, Jing Xiong, Fengkai Wu, Jie Xu, Hai Lan, Qiling Tang, Shufeng Zhou, Yaxi Liu, Yanli Lu
ZEITLUPE (ZTL), LOV KELCH PROTEIN 2 (LKP2), and FLAVIN-BINDING KELCH REPEAT F-BOX 1 (FKF1)-blue-light photoreceptors-play important roles in regulating the circadian clock and photoperiodic flowering pathway in plants. In this study, phylogenetic analysis revealed that the LOV (Light, Oxygen, or Voltage) and Kelch repeat-containing F-box (LFK) gene family can be classified into two clades, ZTL/LKP2 and FKF1, with clear differentiation between monocots and dicots within each clade. The LFK family genes underwent strong purifying selection; however, signatures of positive selection to adapt to local conditions still existed in 18 specific codons...
December 11, 2017: Heredity
https://www.readbyqxmd.com/read/29225034/cytosolic-iron-sulfur-assembly-is-evolutionarily-tuned-by-a-cancer-amplified-ubiquitin-ligase
#16
Jenny L Weon, Seung Wook Yang, Patrick Ryan Potts
The cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) pathway functions to incorporate inorganic Fe-S cofactors into a variety of proteins, including several DNA repair enzymes. However, the mechanisms regulating the CIA pathway are unknown. We describe here that the MAGE-F1-NSE1 E3 ubiquitin ligase regulates the CIA pathway through ubiquitination and degradation of the CIA-targeting protein MMS19. Overexpression or knockout of MAGE-F1 altered Fe-S incorporation into MMS19-dependent DNA repair enzymes, DNA repair capacity, sensitivity to DNA-damaging agents, and iron homeostasis...
November 30, 2017: Molecular Cell
https://www.readbyqxmd.com/read/29222471/spatial-competition-constrains-resistance-to-targeted-cancer-therapy
#17
Katarina Bacevic, Robert Noble, Ahmed Soffar, Orchid Wael Ammar, Benjamin Boszonyik, Susana Prieto, Charles Vincent, Michael E Hochberg, Liliana Krasinska, Daniel Fisher
Adaptive therapy (AT) aims to control tumour burden by maintaining therapy-sensitive cells to exploit their competition with resistant cells. This relies on the assumption that resistant cells have impaired cellular fitness. Here, using a model of resistance to a pharmacological cyclin-dependent kinase inhibitor (CDKi), we show that this assumption is valid when competition between cells is spatially structured. We generate CDKi-resistant cancer cells and find that they have reduced proliferative fitness and stably rewired cell cycle control pathways...
December 8, 2017: Nature Communications
https://www.readbyqxmd.com/read/29221460/goldenpics-a-golden-gate-derived-modular-cloning-system-for-applied-synthetic-biology-in-the-yeast-pichia-pastoris
#18
Roland Prielhofer, Juan J Barrero, Stefanie Steuer, Thomas Gassler, Richard Zahrl, Kristin Baumann, Michael Sauer, Diethard Mattanovich, Brigitte Gasser, Hans Marx
BACKGROUND: State-of-the-art strain engineering techniques for the host Pichia pastoris (syn. Komagataella spp.) include overexpression of homologous and heterologous genes, and deletion of host genes. For metabolic and cell engineering purposes the simultaneous overexpression of more than one gene would often be required. Very recently, Golden Gate based libraries were adapted to optimize single expression cassettes for recombinant proteins in P. pastoris. However, an efficient toolbox allowing the overexpression of multiple genes at once was not available for P...
December 8, 2017: BMC Systems Biology
https://www.readbyqxmd.com/read/29220487/ancestral-genome-estimation-reveals-the-history-of-ecological-diversification-in-agrobacterium
#19
Florent Lassalle, Rémi Planel, Simon Penel, David Chapulliot, Valérie Barbe, Audrey Dubost, Alexandra Calteau, David Vallenet, Damien Mornico, Thomas Bigot, Laurent Guéguen, Ludovic Vial, Daniel Muller, Vincent Daubin, Xavier Nesme
Horizontal gene transfer (HGT) is considered as a major source of innovation in bacteria, and as such is expected to drive adaptation to new ecological niches. However, among the many genes acquired through HGT along the diversification history of genomes, only a fraction may have actively contributed to sustained ecological adaptation. We used a phylogenetic approach accounting for the transfer of genes (or groups of genes) to estimate the history of genomes in Agrobacterium biovar 1, a diverse group of soil and plant-dwelling bacterial species...
December 6, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/29220291/emerging-targeted-and-immune-based-therapies-in-sarcoma
#20
Seth M Pollack, Matthew Ingham, Matthew B Spraker, Gary K Schwartz
Soft tissue and bone sarcomas are malignancies of mesenchymal origin, and more than 50 subtypes are defined. For most sarcomas, locally advanced or unresectable disease is still treated with cytotoxic chemotherapy. Recently, our understanding of subtype-specific cancer biology has expanded, and it has revealed distinct molecular alterations responsible for tumor initiation and progression. These findings have motivated the development of targeted therapies that are being evaluated in subtype-specific or biomarker-driven clinical trials...
December 8, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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