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https://www.readbyqxmd.com/read/29338718/a-live-cell-assay-of-gpcr-coupling-allows-identification-of-optogenetic-tools-for-controlling-go-and-gi-signaling
#1
Edward R Ballister, Jessica Rodgers, Franck Martial, Robert J Lucas
BACKGROUND: Animal opsins are light-sensitive G-protein-coupled receptors (GPCRs) that enable optogenetic control over the major heterotrimeric G-protein signaling pathways in animal cells. As such, opsins have potential applications in both biomedical research and therapy. Selecting the opsin with the best balance of activity and selectivity for a given application requires knowing their ability to couple to a full range of relevant Gα subunits. We present the GsX assay, a set of tools based on chimeric Gs subunits that transduce coupling of opsins to diverse G proteins into increases in cAMP levels,  measured with a real-time reporter in living cells...
January 16, 2018: BMC Biology
https://www.readbyqxmd.com/read/29338710/a-genetically-encoded-ca2-indicator-based-on-circularly-permutated-sea-anemone-red-fluorescent-protein-eqfp578
#2
Yi Shen, Hod Dana, Ahmed S Abdelfattah, Ronak Patel, Jamien Shea, Rosana S Molina, Bijal Rawal, Vladimir Rancic, Yu-Fen Chang, Lanshi Wu, Yingche Chen, Yong Qian, Matthew D Wiens, Nathan Hambleton, Klaus Ballanyi, Thomas E Hughes, Mikhail Drobizhev, Douglas S Kim, Minoru Koyama, Eric R Schreiter, Robert E Campbell
BACKGROUND: Genetically encoded calcium ion (Ca2+) indicators (GECIs) are indispensable tools for measuring Ca2+ dynamics and neuronal activities in vitro and in vivo. Red fluorescent protein (RFP)-based GECIs have inherent advantages relative to green fluorescent protein-based GECIs due to the longer wavelength light used for excitation. Longer wavelength light is associated with decreased phototoxicity and deeper penetration through tissue. Red GECI can also enable multicolor visualization with blue- or cyan-excitable fluorophores...
January 16, 2018: BMC Biology
https://www.readbyqxmd.com/read/29338709/wormachine-machine-learning-based-phenotypic-analysis-tool-for-worms
#3
Adam Hakim, Yael Mor, Itai Antoine Toker, Amir Levine, Moran Neuhof, Yishai Markovitz, Oded Rechavi
BACKGROUND: Caenorhabditis elegans nematodes are powerful model organisms, yet quantification of visible phenotypes is still often labor-intensive, biased, and error-prone. We developed WorMachine, a three-step MATLAB-based image analysis software that allows (1) automated identification of C. elegans worms, (2) extraction of morphological features and quantification of fluorescent signals, and (3) machine learning techniques for high-level analysis. RESULTS: We examined the power of WorMachine using five separate representative assays: supervised classification of binary-sex phenotype, scoring continuous-sexual phenotypes, quantifying the effects of two different RNA interference treatments, and measuring intracellular protein aggregation...
January 16, 2018: BMC Biology
https://www.readbyqxmd.com/read/29334950/will-human-influences-on-evolutionary-dynamics-in-the-wild-pervade-the-anthropocene
#4
REVIEW
Fanie Pelletier, David W Coltman
The five most pervasive anthropogenic threats to biodiversity are over-exploitation, habitat changes, climate change, invasive species, and pollution. Since all of these threats can affect intraspecific biodiversity-including genetic variation within populations-humans have the potential to induce contemporary microevolution in wild populations. We highlight recent empirical studies that have explored the effects of these anthropogenic threats to intraspecific biodiversity in the wild. We conclude that it is critical that we move towards a predictive framework that integrates a better understanding of contemporary microevolution to multiple threats to forecast the fate of natural populations in a changing world...
January 15, 2018: BMC Biology
https://www.readbyqxmd.com/read/29325570/de-novo-assembly-of-the-complex-genome-of-nippostrongylus-brasiliensis-using-minion-long-reads
#5
David Eccles, Jodie Chandler, Mali Camberis, Bernard Henrissat, Sergey Koren, Graham Le Gros, Jonathan J Ewbank
BACKGROUND: Eukaryotic genome assembly remains a challenge in part due to the prevalence of complex DNA repeats. This is a particularly acute problem for holocentric nematodes because of the large number of satellite DNA sequences found throughout their genomes. These have been recalcitrant to most genome sequencing methods. At the same time, many nematodes are parasites and some represent a serious threat to human health. There is a pressing need for better molecular characterization of animal and plant parasitic nematodes...
January 11, 2018: BMC Biology
https://www.readbyqxmd.com/read/29325559/pangenome-analyses-of-the-wheat-pathogen-zymoseptoria-tritici-reveal-the-structural-basis-of-a-highly-plastic-eukaryotic-genome
#6
Clémence Plissonneau, Fanny E Hartmann, Daniel Croll
BACKGROUND: Structural variation contributes substantially to polymorphism within species. Chromosomal rearrangements that impact genes can lead to functional variation among individuals and influence the expression of phenotypic traits. Genomes of fungal pathogens show substantial chromosomal polymorphism that can drive virulence evolution on host plants. Assessing the adaptive significance of structural variation is challenging, because most studies rely on inferences based on a single reference genome sequence...
January 11, 2018: BMC Biology
https://www.readbyqxmd.com/read/29329541/a-role-for-endothelial-nitric-oxide-synthase-in-intestinal-stem-cell-proliferation-and-mesenchymal-colorectal-cancer
#7
Jon Peñarando, Laura M López-Sánchez, Rafael Mena, Silvia Guil-Luna, Francisco Conde, Vanessa Hernández, Marta Toledano, Victoria Gudiño, Michela Raponi, Caroline Billard, Carlos Villar, César Díaz, José Gómez-Barbadillo, Juan De la Haba-Rodríguez, Kevin Myant, Enrique Aranda, Antonio Rodríguez-Ariza
BACKGROUND: Nitric oxide (NO) has been highlighted as an important agent in cancer-related events. Although the inducible nitric oxide synthase (iNOS) isoform has received most attention, recent studies in the literature indicate that the endothelial isoenzyme (eNOS) can also modulate different tumor processes including resistance, angiogenesis, invasion, and metastasis. However, the role of eNOS in cancer stem cell (CSC) biology and mesenchymal tumors is unknown. RESULTS: Here, we show that eNOS was significantly upregulated in VilCre ERT2 Apc fl/+ and VilCre ERT2 Apc fl/fl mouse intestinal tissue, with intense immunostaining in hyperproliferative crypts...
January 10, 2018: BMC Biology
https://www.readbyqxmd.com/read/29325568/pink1-import-regulation-a-fine-system-to-convey-mitochondrial-stress-to-the-cytosol
#8
REVIEW
Shiori Sekine, Richard J Youle
Insights from inherited forms of parkinsonism suggest that insufficient mitophagy may be one etiology of the disease. PINK1/Parkin-dependent mitophagy, which helps maintain a healthy mitochondrial network, is initiated by activation of the PINK1 kinase specifically on damaged mitochondria. Recent investigation of this process reveals that import of PINK1 into mitochondria is regulated and yields a stress-sensing mechanism. In this review, we focus on the mechanisms of mitochondrial stress-dependent PINK1 activation that is exerted by regulated import of PINK1 into different mitochondrial compartments and how this offers strategies to pharmacologically activate the PINK1/Parkin pathway...
January 10, 2018: BMC Biology
https://www.readbyqxmd.com/read/29325558/systematic-target-function-annotation-of-human-transcription-factors
#9
Yong Fuga Li, Russ B Altman
BACKGROUND: Transcription factors (TFs), the key players in transcriptional regulation, have attracted great experimental attention, yet the functions of most human TFs remain poorly understood. Recent capabilities in genome-wide protein binding profiling have stimulated systematic studies of the hierarchical organization of human gene regulatory network and DNA-binding specificity of TFs, shedding light on combinatorial gene regulation. We show here that these data also enable a systematic annotation of the biological functions and functional diversity of TFs...
January 10, 2018: BMC Biology
https://www.readbyqxmd.com/read/29325545/phthiocerol-dimycocerosates-promote-access-to-the-cytosol-and-intracellular-burden-of-mycobacterium-tuberculosis-in-lymphatic-endothelial-cells
#10
Thomas R Lerner, Christophe J Queval, Antony Fearns, Urska Repnik, Gareth Griffiths, Maximiliano G Gutierrez
BACKGROUND: Phthiocerol dimycocerosates (PDIM), glycolipids found on the outer surface of virulent members of the Mycobacterium tuberculosis (Mtb) complex, are a major contributing factor to the pathogenesis of Mtb. Myelocytic cells, such as macrophages and dendritic cells, are the primary hosts for Mtb after infection and previous studies have shown multiple roles for PDIM in supporting Mtb in these cells. However, Mtb can infect other cell types. We previously showed that Mtb efficiently replicates in human lymphatic endothelial cells (hLECs) and that the hLEC cytosol acts as a reservoir for Mtb in humans...
January 4, 2018: BMC Biology
https://www.readbyqxmd.com/read/29282124/memory-retrieval-in-addiction-a-role-for-mir-105-mediated-regulation-of-d1-receptors-in-mpfc-neurons-projecting-to-the-basolateral-amygdala
#11
Yanfang Zhao, Junfang Zhang, Hualan Yang, Dongyang Cui, Jiaojiao Song, Qianqian Ma, Wenjie Luan, Bin Lai, Lan Ma, Ming Chen, Ping Zheng
BACKGROUND: Drug addiction is a chronic brain disorder characterized by the compulsive use of drugs. The study of chronic morphine-induced adaptation in the brain and its functional significance is of importance to understand the mechanism of morphine addiction. Previous studies have found a number of chronic morphine-induced adaptive changes at molecular levels in the brain. A study from our lab showed that chronic morphine-induced increases in the expression of D1 receptors at presynaptic terminals coming from other structures to the basolateral amygdala (BLA) played an important role in environmental cue-induced retrieval of morphine withdrawal memory...
December 27, 2017: BMC Biology
https://www.readbyqxmd.com/read/29282064/q-a-friends-but-sometimes-foes-within-the-complex-evolutionary-ecology-of-symbioses-between-host-and-microbes
#12
Nicole Gerardo, Gregory Hurst
Over the past decade, there has been a pronounced shift in the study of host-microbe associations, with recognition that many of these associations are beneficial, and often critical, for a diverse array of hosts. There may also be pronounced benefits for the microbes, though this is less well empirically understood. Significant progress has been made in understanding how ecology and evolution shape simple associations between hosts and one or a few microbial species, and this work can serve as a foundation to study the ecology and evolution of host associations with their often complex microbial communities (microbiomes)...
December 27, 2017: BMC Biology
https://www.readbyqxmd.com/read/29282061/the-human-microbiome-in-evolution
#13
REVIEW
Emily R Davenport, Jon G Sanders, Se Jin Song, Katherine R Amato, Andrew G Clark, Rob Knight
The trillions of microbes living in the gut-the gut microbiota-play an important role in human biology and disease. While much has been done to explore its diversity, a full understanding of our microbiomes demands an evolutionary perspective. In this review, we compare microbiomes from human populations, placing them in the context of microbes from humanity's near and distant animal relatives. We discuss potential mechanisms to generate host-specific microbiome configurations and the consequences of disrupting those configurations...
December 27, 2017: BMC Biology
https://www.readbyqxmd.com/read/29268741/the-toll-pathway-underlies-host-sexual-dimorphism-in-resistance-to-both-gram-negative-and-gram-positive-bacteria-in-mated-drosophila
#14
David F Duneau, Hannah C Kondolf, Joo Hyun Im, Gerardo A Ortiz, Christopher Chow, Michael A Fox, Ana T Eugénio, J Revah, Nicolas Buchon, Brian P Lazzaro
BACKGROUND: Host sexual dimorphism is being increasingly recognized to generate strong differences in the outcome of infectious disease, but the mechanisms underlying immunological differences between males and females remain poorly characterized. Here, we used Drosophila melanogaster to assess and dissect sexual dimorphism in the innate response to systemic bacterial infection. RESULTS: We demonstrated sexual dimorphism in susceptibility to infection by a broad spectrum of Gram-positive and Gram-negative bacteria...
December 21, 2017: BMC Biology
https://www.readbyqxmd.com/read/29268740/an-elevated-plus-maze-in-mixed-reality-for-studying-human-anxiety-related-behavior
#15
Sarah V Biedermann, Daniel G Biedermann, Frederike Wenzlaff, Tim Kurjak, Sawis Nouri, Matthias K Auer, Klaus Wiedemann, Peer Briken, Jan Haaker, Tina B Lonsdorf, Johannes Fuss
BACKGROUND: A dearth of laboratory tests to study actual human approach-avoidance behavior has complicated translational research on anxiety. The elevated plus-maze (EPM) is the gold standard to assess approach-avoidance behavior in rodents. METHODS: Here, we translated the EPM to humans using mixed reality through a combination of virtual and real-world elements. In two validation studies, we observed participants' anxiety on a behavioral, physiological, and subjective level...
December 21, 2017: BMC Biology
https://www.readbyqxmd.com/read/29268736/q-a-why-use-synchrotron-x-ray-tomography-for-multi-scale-connectome-mapping
#16
Yeukuang Hwu, Giorgio Margaritondo, Ann-Shyn Chiang
To understand how information flows and is used in the human brain, we must map neural structures at all levels, providing visualizations similar to those of Google Earth for continents, countries, cities, and streets. Unfortunately, the imaging and processing techniques currently used in connectomics projects cannot achieve complete mapping for the brains of large animals within the timespan of a typical research career. However, feasible improvements in x-ray imaging would change this situation. This Q&A discusses synchrotron x-ray tomography, an exciting new approach for in situ mapping of whole-brain wiring diagrams at multiple levels of spatial resolution...
December 21, 2017: BMC Biology
https://www.readbyqxmd.com/read/29268734/outer-membrane-protein-folding-from-an-energy-landscape-perspective
#17
REVIEW
Bob Schiffrin, David J Brockwell, Sheena E Radford
The cell envelope is essential for the survival of Gram-negative bacteria. This specialised membrane is densely packed with outer membrane proteins (OMPs), which perform a variety of functions. How OMPs fold into this crowded environment remains an open question. Here, we review current knowledge about OMP folding mechanisms in vitro and discuss how the need to fold to a stable native state has shaped their folding energy landscapes. We also highlight the role of chaperones and the β-barrel assembly machinery (BAM) in assisting OMP folding in vivo and discuss proposed mechanisms by which this fascinating machinery may catalyse OMP folding...
December 21, 2017: BMC Biology
https://www.readbyqxmd.com/read/29262826/investigating-the-physiology-of-viable-but-non-culturable-bacteria-by-microfluidics-and-time-lapse-microscopy
#18
Rosemary A Bamford, Ashley Smith, Jeremy Metz, Georgina Glover, Richard W Titball, Stefano Pagliara
BACKGROUND: Clonal microbial populations often harbor rare phenotypic variants that are typically hidden within the majority of the remaining cells, but are crucial for the population's resilience to external perturbations. Persister and viable but non-culturable (VBNC) cells are two important clonal bacterial subpopulations that can survive antibiotic treatment. Both persister and VBNC cells pose a serious threat to human health. However, unlike persister cells, which quickly resume growth following drug removal, VBNC cells can remain non-growing for prolonged periods of time, thus eluding detection via traditional microbiological assays...
December 21, 2017: BMC Biology
https://www.readbyqxmd.com/read/29241459/to-mia-or-not-to-mia-stepwise-evolution-of-the-mitochondrial-intermembrane-space-disulfide-relay
#19
LETTER
Chris Carrie, Jürgen Soll
The disulfide relay system found in the intermembrane space (IMS) of mitochondria is an essential pathway for the import and oxidative folding of IMS proteins. Erv1, an essential member of this pathway, has been previously found to be ubiquitously present in mitochondria-containing eukaryotes. However, the other essential protein, Mia40, was found to be absent or not required in some organisms, raising questions about how the disulfide relay functions in these organisms. A recent study published in BMC Biology demonstrates for the first time that some Erv1 proteins can function in oxidative folding independently of a Mia40 protein, providing for the first time strong evidence that the IMS disulfide relay evolved in a stepwise manner...
December 14, 2017: BMC Biology
https://www.readbyqxmd.com/read/29241453/bile-acid-is-a-significant-host-factor-shaping-the-gut-microbiome-of-diet-induced-obese-mice
#20
Xiaojiao Zheng, Fengjie Huang, Aihua Zhao, Sha Lei, Yunjing Zhang, Guoxiang Xie, Tianlu Chen, Chun Qu, Cynthia Rajani, Bing Dong, Defa Li, Wei Jia
BACKGROUND: Intestinal bacteria are known to regulate bile acid (BA) homeostasis via intestinal biotransformation of BAs and stimulation of the expression of fibroblast growth factor 19 through intestinal nuclear farnesoid X receptor (FXR). On the other hand, BAs directly regulate the gut microbiota with their strong antimicrobial activities. It remains unclear, however, how mammalian BAs cross-talk with gut microbiome and shape microbial composition in a dynamic and interactive way. RESULTS: We quantitatively profiled small molecule metabolites derived from host-microbial co-metabolism in mice, demonstrating that BAs were the most significant factor correlated with microbial alterations among all types of endogenous metabolites...
December 14, 2017: BMC Biology
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