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adaptive pathways

Kathryn S Carpentier, Nicolle M Esparo, Stephanie J Child, Adam P Geballe
During millions of years of coevolution with their hosts, cytomegaloviruses (CMVs) have succeeded in adapting to overcome host-specific immune defenses, including the protein kinase R (PKR) pathway. Consequently, these adaptations may also contribute to the inability of CMVs to cross species barriers. Here, we provide evidence that the evolutionary arms race between the antiviral factor PKR and its CMV antagonist TRS1 has led to extensive differences in the species-specificity of primate CMV TRS1 proteins. Moreover, we identify a single residue in human PKR that when mutated to the amino acid present in African green monkey (Agm) PKR (F489S) is sufficient to confer resistance to HCMVTRS1...
October 2016: PLoS Pathogens
Daniel M Bear, Jean-Marc Lassance, Hopi E Hoekstra, Sandeep Robert Datta
Evolution sculpts the olfactory nervous system in response to the unique sensory challenges facing each species. In vertebrates, dramatic and diverse adaptations to the chemical environment are possible because of the hierarchical structure of the olfactory receptor (OR) gene superfamily: expansion or contraction of OR subfamilies accompanies major changes in habitat and lifestyle; independent selection on OR subfamilies can permit local adaptation or conserved chemical communication; and genetic variation in single OR genes can alter odor percepts and behaviors driven by precise chemical cues...
October 24, 2016: Current Biology: CB
Matthew C Choy, Kumar Visvanathan, Peter De Cruz
Inflammatory bowel diseases (IBDs) are thought to develop as a result of complex interactions between host genetics, the immune system and the environment including the gut microbiome. Although an improved knowledge of the immunopathogenesis of IBDs has led to great advances in therapy such as the highly effective anti-tumor necrosis factor class of medications, a significant proportion of patients with Crohn's disease and ulcerative colitis do not respond to anti-tumor necrosis factor antibodies. Further understanding of the different immune pathways involved in the genesis of chronic intestinal inflammation is required to help find effective treatments for IBDs...
October 21, 2016: Inflammatory Bowel Diseases
Kanishka Senarath, Kasun Ratnayake, Praneeth Siripurapu, John L Payton, Ajith Karunarathne
Current assays to measure the activation of G protein coupled receptors (GPCRs) and G proteins are time consuming, indirect and expensive. Therefore, an efficient method which directly measures the ability of a ligand to govern GPCR-G protein interactions can help understand the molecular underpinnings of the associated signaling. A live cell imaging based approach is presented here to directly measure ligand-induced GPCR and G protein activity in real time. The number of active GPCRs governs G protein heterotrimer (αβγ) dissociation, thereby controlling the concentration of free βγ subunits...
October 25, 2016: Analytical Chemistry
Bose Karthikeyan, Lakshminarasimhan Harini, Vaithilingam Krishnakumar, Velu Rajesh Kannan, Krishnan Sundar, Thandavarayan Kathiresan
Endoplasmic reticulum (ER) stress-mediated apoptosis is a well-known factor in the pathogenesis of age-related macular degeneration (AMD). ER stress leads to accumulation of misfolded proteins, which in turn activates unfolded protein response (UPR) of the cell for its survival. The prolonged UPR of ER stress promotes cell death; however, the transition between adaptation and ER stress-induced apoptosis has not been clearly understood. Hence, the present study investigates the regulatory effect of (-)-epigallocatechin gallate (EGCG) on ER stress-induced by hydrogen peroxide (H2O2) and disturbance of calcium homeostasis by thapsigargin (TG) in mouse retinal pigment epithelial (MRPE) cells...
October 24, 2016: Apoptosis: An International Journal on Programmed Cell Death
Katrien H P Van Petegem, David Renault, Robby Stoks, Dries Bonte
Despite an increasing number of studies documenting life-history evolution during range expansions or shifts, we lack a mechanistic understanding of the underlying physiological processes. In this explorative study, we used a metabolomics approach to study physiological changes associated with the recent range expansion of the two-spotted spider mite (Tetranychus urticae). Mite populations were sampled along a latitudinal gradient from range core to edge and reared under benign common garden conditions for two generations...
September 2016: Ecology and Evolution
Donna M Bond, Nick W Albert, Robyn H Lee, Gareth B Gillard, Chris M Brown, Roger P Hellens, Richard C Macknight
BACKGROUND: Transcription factors (TFs) coordinate precise gene expression patterns that give rise to distinct phenotypic outputs. The identification of genes and transcriptional networks regulated by a TF often requires stable transformation and expression changes in plant cells. However, the production of stable transformants can be slow and laborious with no guarantee of success. Furthermore, transgenic plants overexpressing a TF of interest can present pleiotropic phenotypes and/or result in a high number of indirect gene expression changes...
2016: Plant Methods
Lianghua Bin, Donald Y M Leung
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory disease caused by the complex interaction of genetic, immune and environmental factors. There have many recent discoveries involving the genetic and epigenetic studies of AD. METHODS: A retrospective PubMed search was carried out from June 2009 to June 2016 using the terms "atopic dermatitis", "association", "eczema", "gene", "polymorphism", "mutation", "variant", "genome wide association study", "microarray" "gene profiling", "RNA sequencing", "epigenetics" and "microRNA"...
2016: Allergy, Asthma, and Clinical Immunology
Kelly D Moynihan, Cary F Opel, Gregory L Szeto, Alice Tzeng, Eric F Zhu, Jesse M Engreitz, Robert T Williams, Kavya Rakhra, Michael H Zhang, Adrienne M Rothschilds, Sudha Kumari, Ryan L Kelly, Byron H Kwan, Wuhbet Abraham, Kevin Hu, Naveen K Mehta, Monique J Kauke, Heikyung Suh, Jennifer R Cochran, Douglas A Lauffenburger, K Dane Wittrup, Darrell J Irvine
Checkpoint blockade with antibodies specific for cytotoxic T lymphocyte-associated protein (CTLA)-4 or programmed cell death 1 (PDCD1; also known as PD-1) elicits durable tumor regression in metastatic cancer, but these dramatic responses are confined to a minority of patients. This suboptimal outcome is probably due in part to the complex network of immunosuppressive pathways present in advanced tumors, which are unlikely to be overcome by intervention at a single signaling checkpoint. Here we describe a combination immunotherapy that recruits a variety of innate and adaptive immune cells to eliminate large tumor burdens in syngeneic tumor models and a genetically engineered mouse model of melanoma; to our knowledge tumors of this size have not previously been curable by treatments relying on endogenous immunity...
October 24, 2016: Nature Medicine
Ursula N Broder, Tina Jaeger, Urs Jenal
Virulence of pathogenic bacteria is a tightly controlled process to facilitate invasion and survival in host tissues. Although pathways controlling virulence have been defined in detail, signals modulating these processes are poorly understood. The opportunistic pathogen Pseudomonas aeruginosa causes acute and chronic infections in humans. Disease progression is typically associated with a loss of acute virulence and the emergence of biofilms and chronic behaviour. The acute-to-chronic switch is governed by the global Gac/Rsm pathway...
October 24, 2016: Nature Microbiology
Hanna Starobinets, Jordan Ye, Miranda Broz, Kevin Barry, Juliet Goldsmith, Timothy Marsh, Fanya Rostker, Matthew Krummel, Jayanta Debnath
The rising success of cancer immunotherapy has produced immense interest in defining the clinical contexts that may benefit from this therapeutic approach. To this end, there is a need to ascertain how the therapeutic modulation of intrinsic cancer cell programs influences the anticancer immune response. For example, the role of autophagy as a tumor cell survival and metabolic fitness pathway is being therapeutically targeted in ongoing clinical trials that combine cancer therapies with antimalarial drugs for the treatment of a broad spectrum of cancers, many of which will likely benefit from immunotherapy...
October 24, 2016: Journal of Clinical Investigation
Nelli Erwin, Satyajit Patra, Roland Winter
The ubiquitous Ca(2+)-sensing protein calmodulin (CaM) interacts with more than 300 diverse target proteins that are involved in numerous signaling pathways in eukaryotic cells. This unique promiscuous target binding behavior and the underlying functional versatility of CaM is a result of its structural flexibility. CaM spans multiple conformational substates in solution providing adaptable binding surfaces for different target proteins. The conformational space of this protein needs to be explored to shed more light on the mechanism of target recognition and protein function...
October 24, 2016: Physical Chemistry Chemical Physics: PCCP
Juanjuan Zhao, Chao Chen, Mengmeng Guo, Yijin Tao, PanPan Cui, Ya Zhou, Nalin Qin, Jing Zheng, Jidong Zhang, Lin Xu
Recent evidence showed that microRNA-7 (miR-7) played an important role in the pathologies of lung-related diseases. However, the potential role of miR-7 in acute lung injury (ALI) still remains poorly understood. Here, we assessed the effect of miR-7 deficiency on the pathology of ALI. We, first, found that the expression of miR-7 was upregulated in lung tissue in murine LPS-induced ALI model. Notably, we generated miR-7 knock down mice by using miRNA-Sponge technique and found that miR-7 deficiency could ameliorate the pathologies of lung as evidenced by accelerated body weight recovery, reduced level of bronchoalveolar lavage (BAL) proinflammatory cytokines and decreased number of BAL cells in ALI mice...
2016: Frontiers in Immunology
Clara Bien Peek, Daniel C Levine, Jonathan Cedernaes, Akihiko Taguchi, Yumiko Kobayashi, Stacy J Tsai, Nicolle A Bonar, Maureen R McNulty, Kathryn Moynihan Ramsey, Joseph Bass
Circadian clocks are encoded by a transcription-translation feedback loop that aligns energetic processes with the solar cycle. We show that genetic disruption of the clock activator BMAL1 in skeletal myotubes and fibroblasts increased levels of the hypoxia-inducible factor 1α (HIF1α) under hypoxic conditions. Bmal1(-/-) myotubes displayed reduced anaerobic glycolysis, mitochondrial respiration with glycolytic fuel, and transcription of HIF1α targets Phd3, Vegfa, Mct4, Pk-m, and Ldha, whereas abrogation of the clock repressors CRY1/2 stabilized HIF1α in response to hypoxia...
October 19, 2016: Cell Metabolism
Silvia Celletti, Youry Pii, Tanja Mimmo, Stefano Cesco, Stefania Astolfi
Plant mechanisms responding to iron (Fe) deficiency have been widely described; it is well known that Strategy II plants, as durum wheat, cope with this stress by increasing both the synthesis and secretion of phytosiderophores (PS). The important contribution of the sulfate assimilatory pathway has been also demonstrated to improve Fe use efficiency in several grasses, such as maize, barley and wheat, most likely because PS are produced from nicotianamine, whose precursor is methionine. Here, the physiological response of durum wheat (T...
October 13, 2016: Plant Physiology and Biochemistry: PPB
Sergio Rey, Luana Schito, Marianne Koritzinsky, Bradly G Wouters
Hypoxia (low O2) is an essential microenvironmental driver of phenotypic diversity in human solid cancers. Hypoxic cancer cells hijack evolutionarily conserved, O2- sensitive pathways eliciting molecular adaptations that impact responses to radiotherapy, tumor recurrence and patient survival. In this review, we summarize the radiobiological, genetic, epigenetic and metabolic mechanisms orchestrating oncogenic responses to hypoxia. In addition, we outline emerging hypoxia- targeting strategies that hold promise for individualized cancer therapy in the context of radiotherapy and drug delivery...
October 19, 2016: Advanced Drug Delivery Reviews
Kathy A Schall, Kathleen A Holoyda, Mubina Isani, Ching-Ling Lien, Denise Al Alam, Tracy C Grikscheit
BACKGROUND: Signaling by fibroblast growth factor is critical for epithelial proliferation, differentiation, and the development of many organs, including the intestine. Fibroblast growth factor 10 and fibroblast growth factor 2c are upregulated after massive bowel resection during intestinal adaptation. This pathway is conserved highly. We hypothesized that inhibition of fibroblast growth factor signaling would impair intestinal adaptation in the zebrafish model of short bowel syndrome and allow insight into the negative regulation of this pathway...
October 19, 2016: Surgery
Seung Jae Lee, Eun-Mi Jeong, Ah Young Ki, Kyung-Seo Oh, Joseph Kwon, Jae-Hyuk Jeong, Nam-Jin Chung
High salinity is a major abiotic stress that affects the growth and development of plants. This type of stress can influence flowering, the production of crops, defense mechanisms and other physiological processes. Previous studies have attempted to elucidate salt-tolerance mechanisms to improve plant growth and productivity in the presence of sodium chloride. One such plant that has been studied in detail is Salicornia, a well-known halophyte, which has adapted to grow in the presence of high salt. To further the understanding of how Salicornia grows and develops under high saline conditions, Salicornia herbacea (S...
September 29, 2016: Journal of Plant Physiology
Masayuki Tsuzuki, Yuichiro Watanabe
Small RNAs are key molecules in RNA silencing pathways that exert the sequence-specific regulation of gene expression and chromatin modifications in many eukaryotes. In plants, endogenous small RNAs, including microRNAs (miRNAs), trans-acting short interfering RNAs (tasiRNAs), and heterochromatic siRNAs (hc-siRNAs), play an important role in switching or orchestrating biological processes during the development and at the onset of stress responses. These endogenous and exogenous small RNAs are mainly 20-24 nucleotides in length...
2017: Methods in Molecular Biology
J Slieker, P Frauche, J Jurt, V Addor, C Blanc, Nicolas Demartines, M Hübner
BACKGROUND: Enhanced recovery after surgery (ERAS) pathway includes recovery goals requiring active participation of the patients; this may be perceived as "aggressive" care in older patients. The aim of the present study was to assess whether ERAS was feasible and beneficial in older patients. METHODS: Since June 2011, all consecutive colorectal patients were included in an ERAS pathway and documented in a dedicated prospective database. This retrospective analysis included 513 patients, 311 younger patients (<70 years) and 202 older patients (≥70 years)...
October 21, 2016: International Journal of Colorectal Disease
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