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https://www.readbyqxmd.com/read/28423062/filamentous-fungal-carbon-catabolite-repression-supports-metabolic-plasticity-and-stress-responses-essential-for-disease-progression
#1
Sarah R Beattie, Kenneth M K Mark, Arsa Thammahong, Laure Nicolas Annick Ries, Sourabh Dhingra, Alayna K Caffrey-Carr, Chao Cheng, Candice C Black, Paul Bowyer, Michael J Bromley, Joshua J Obar, Gustavo H Goldman, Robert A Cramer
Aspergillus fumigatus is responsible for a disproportionate number of invasive mycosis cases relative to other common filamentous fungi. While many fungal factors critical for infection establishment are known, genes essential for disease persistence and progression are ill defined. We propose that fungal factors that promote navigation of the rapidly changing nutrient and structural landscape characteristic of disease progression represent untapped clinically relevant therapeutic targets. To this end, we find that A...
April 19, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28396388/altering-the-allosteric-pathway-in-igps-suppresses-millisecond-motions-and-catalytic-activity
#2
George P Lisi, Kyle W East, Victor S Batista, J Patrick Loria
Imidazole glycerol phosphate synthase (IGPS) is a V-type allosteric enzyme, meaning that its catalytic rate is critically dependent on activation by its allosteric ligand, N'-[(5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamide ribonucleotide (PRFAR). The allosteric mechanism of IGPS is reliant on millisecond conformational motions for efficient catalysis. We engineered four mutants of IGPS designed to disrupt millisecond motions and allosteric coupling to identify regions that are critical to IGPS function...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28387346/plk1-regulates-the-repressor-function-of-foxm1b-by-inhibiting-its-interaction-with-the-retinoblastoma-protein
#3
Nishit K Mukhopadhyay, Vaibhav Chand, Akshay Pandey, Dragana Kopanja, Janai R Carr, Yi-Ju Chen, Xiubei Liao, Pradip Raychaudhuri
FoxM1b is a cell cycle-regulated transcription factor, whose over-expression is a marker for poor outcome in cancers. Its transcriptional activation function requires phosphorylation by Cdk1 or Cdk2 that primes FoxM1b for phosphorylation by Plk1, which triggers association with the co-activator CBP. FoxM1b also possesses transcriptional repression function. It represses the mammary differentiation gene GATA3 involving DNMT3b and Rb. We investigated what determines the two distinct functions of FoxM1b: activation and repression...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28385571/aging-mobility-impairments-and-subjective-wellbeing
#4
Vicki A Freedman, Deborah Carr, Jennifer C Cornman, Richard E Lucas
BACKGROUND: Wellbeing is often described as U-shaped over the life course, suggesting an apparent paradox that wellbeing remains high at older ages despite increases in impairments. OBJECTIVE/HYPOTHESES: We explore associations among age, lower body impairments-one of the most common late-life impairments-and three measures of wellbeing: life satisfaction, emotional wellbeing and somatic wellbeing. We hypothesize that age effects are positive, become stronger once lower body impairments are controlled, and are concentrated among those who have maintained their mobility...
March 22, 2017: Disability and Health Journal
https://www.readbyqxmd.com/read/28346141/insights-into-electrosensory-organ-development-physiology-and-evolution-from-a-lateral-line-enriched-transcriptome
#5
Melinda S Modrell, Mike Lyne, Adrian R Carr, Harold H Zakon, David Buckley, Alexander S Campbell, Marcus C Davis, Gos Micklem, Clare Vh Baker
The anamniote lateral line system, comprising mechanosensory neuromasts and electrosensory ampullary organs, is a useful model for investigating the developmental and evolutionary diversification of different organs and cell types. Zebrafish neuromast development is increasingly well understood, but neither zebrafish nor Xenopus is electroreceptive and our molecular understanding of ampullary organ development is rudimentary. We have used RNA-seq to generate a lateral line-enriched gene-set from late-larval paddlefish (Polyodon spathula)...
March 27, 2017: ELife
https://www.readbyqxmd.com/read/28295099/sensitivity-evaluation-of-quantitative-phase-imaging-a-study-of-wavelength-shifting-interferometry
#6
Shichao Chen, Chengshuai Li, Yizheng Zhu
Sensitivity is a critical figure of merit to quantify measurement performance in quantitative phase imaging. It is affected by various noise sources in the system and by signal processing algorithms. Here we propose a three-level framework for sensitivity evaluation, including the Cramér-Rao bound (CRB), algorithmic sensitivity, and experimental sensitivity. Comparing the first two determines the theoretical efficiency of an algorithm, while inspecting the gap between the latter two reveals system efficiency...
March 15, 2017: Optics Letters
https://www.readbyqxmd.com/read/28259727/vision-of-the-body-improves-inter-hemispheric-integration-of-tactile-motor-responses
#7
Luigi Tamè, Alex Carr, Matthew R Longo
Sensory input from and motor output to the two sides of the body needs to be continuously integrated between the two cerebral hemispheres. This integration can be measured through its cost in terms of processing speed. In simple detection tasks, reaction times (RTs) are faster when stimuli are presented to the side of the body ipsilateral to the body part used to respond. This advantage - the contralateral-ipsilateral difference (also known as the crossed-uncrossed difference: CUD) - is thought to reflect inter-hemispheric interactions needed for sensorimotor information to be integrated between the two hemispheres...
March 2, 2017: Acta Psychologica
https://www.readbyqxmd.com/read/28257503/depletion-of-enteric-bacteria-diminishes-leukocyte-infiltration-following-doxorubicin-induced-small-intestinal-damage-in-mice
#8
Jacquelyn S Carr, Stephanie King, Christopher M Dekaney
BACKGROUND & AIMS: While enteric bacteria have been shown to play a critical role in other forms of intestinal damage, their role in mediating the response to the chemotherapeutic drug Doxorubicin (Doxo) is unclear. In this study, we used a mouse model of intestinal bacterial depletion to evaluate the role enteric bacteria play in mediating Doxo-induced small intestinal damage and, more specifically, in mediating chemokine expression and leukocyte infiltration following Doxo treatment...
2017: PloS One
https://www.readbyqxmd.com/read/28228285/mass-spectrometry-profiling-of-hla-associated-peptidomes-in-mono-allelic-cells-enables-more-accurate-epitope-prediction
#9
Jennifer G Abelin, Derin B Keskin, Siranush Sarkizova, Christina R Hartigan, Wandi Zhang, John Sidney, Jonathan Stevens, William Lane, Guang Lan Zhang, Thomas M Eisenhaure, Karl R Clauser, Nir Hacohen, Michael S Rooney, Steven A Carr, Catherine J Wu
Identification of human leukocyte antigen (HLA)-bound peptides by liquid chromatography-tandem mass spectrometry (LC-MS/MS) is poised to provide a deep understanding of rules underlying antigen presentation. However, a key obstacle is the ambiguity that arises from the co-expression of multiple HLA alleles. Here, we have implemented a scalable mono-allelic strategy for profiling the HLA peptidome. By using cell lines expressing a single HLA allele, optimizing immunopurifications, and developing an application-specific spectral search algorithm, we identified thousands of peptides bound to 16 different HLA class I alleles...
February 21, 2017: Immunity
https://www.readbyqxmd.com/read/28215810/the-impact-of-pre-restoration-land-use-and-disturbance-on-sediment-structure-hydrology-and-the-sediment-geochemical-environment-in-restored-saltmarshes
#10
Kate L Spencer, Simon J Carr, Lucy M Diggens, James A Tempest, Michelle A Morris, Gemma L Harvey
Saltmarshes are being lost or degraded as a result of human activity resulting in loss of critical ecosystem services including the provision of wild species diversity, water quality regulation and flood regulation. To compensate, saltmarshes are being restored or re-created, usually driven by legislative requirements for increased habitat diversity, flood regulation and sustainable coastal defense. Yet, there is increasing evidence that restoration may not deliver anticipated ecosystem services; this is frequently attributed to poor drainage and sediment anoxia...
February 16, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28125659/biodiversity-areas-under-threat-overlap-of-climate-change-and-population-pressures-on-the-world-s-biodiversity-priorities
#11
Juliann E Aukema, Narcisa G Pricope, Gregory J Husak, David Lopez-Carr
Humans and the ecosystem services they depend on are threatened by climate change. Places with high or growing human population as well as increasing climate variability, have a reduced ability to provide ecosystem services just as the need for these services is most critical. A spiral of vulnerability and ecosystem degradation often ensues in such places. We apply different global conservation schemes as proxies to examine the spatial relation between wet season precipitation, population change over three decades, and natural resource conservation...
2017: PloS One
https://www.readbyqxmd.com/read/28125254/is-that-a-human-categorization-dis-fluency-drives-evaluations-of-agents-ambiguous-on-human-likeness
#12
Evan W Carr, Galit Hofree, Kayla Sheldon, Ayse P Saygin, Piotr Winkielman
A fundamental and seemingly unbridgeable psychological boundary divides humans and nonhumans. Essentialism theories suggest that mixing these categories violates "natural kinds." Perceptual theories propose that such mixing creates incompatible cues. Most theories suggest that mixed agents, with both human and nonhuman features, obligatorily elicit discomfort. In contrast, we demonstrate top-down, cognitive control of these effects-such that the discomfort with mixed agents is partially driven by disfluent categorization of ambiguous features that are pertinent to the agent...
April 2017: Journal of Experimental Psychology. Human Perception and Performance
https://www.readbyqxmd.com/read/28116356/tambora-and-the-mackerel-year-phenology-and-fisheries-during-an-extreme-climate-event
#13
Karen E Alexander, William B Leavenworth, Theodore V Willis, Carolyn Hall, Steven Mattocks, Steven M Bittner, Emily Klein, Michelle Staudinger, Alexander Bryan, Julianne Rosset, Benjamin H Carr, Adrian Jordaan
Global warming has increased the frequency of extreme climate events, yet responses of biological and human communities are poorly understood, particularly for aquatic ecosystems and fisheries. Retrospective analysis of known outcomes may provide insights into the nature of adaptations and trajectory of subsequent conditions. We consider the 1815 eruption of the Indonesian volcano Tambora and its impact on Gulf of Maine (GoM) coastal and riparian fisheries in 1816. Applying complex adaptive systems theory with historical methods, we analyzed fish export data and contemporary climate records to disclose human and piscine responses to Tambora's extreme weather at different spatial and temporal scales while also considering sociopolitical influences...
January 2017: Science Advances
https://www.readbyqxmd.com/read/28095684/effect-of-the-protein-corona-on-antibody-antigen-binding-in-nanoparticle-sandwich-immunoassays
#14
Helena de Puig, Irene Bosch, Marc Carré-Camps, Kimberly Hamad-Schifferli
We investigated the effect of the protein corona on the function of nanoparticle (NP) antibody (Ab) conjugates in dipstick sandwich immunoassays. Ab specific for Zika virus nonstructural protein 1 (NS1) were conjugated to gold NPs, and another anti-NS1 Ab was immobilized onto the nitrocellulose membrane. Sandwich immunoassay formation was influenced by whether the strip was run in corona forming conditions, i.e., in human serum. Strips run in buffer or pure solutions of bovine serum albumin exhibited false positives, but those run in human serum did not...
January 18, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28074831/rgs9-2-modulates-responses-to-oxycodone-in-pain-free-and-chronic-pain-states
#15
Sevasti Gaspari, Valeria Cogliani, Lefteris Manouras, Ethan M Anderson, Vasiliki Mitsi, Kleopatra Avrampou, Fiona B Carr, Venetia Zachariou
Regulator of G protein signalling 9-2 (RGS9-2) is a striatal enriched signal transduction modulator, known to play a critical role in the development of addiction-related behaviours following exposure to psychostimulants or opioids. RGS9-2 controls the function of several GPCRs, including dopamine and mu opioid (MOR) receptors. We previously showed that RGS9-2 complexes negatively control morphine analgesia, and promote the development of morphine tolerance. In contrast, RGS9-2 positively modulates the actions of other opioid analgesics, such as fentanyl and methadone...
January 11, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28071719/quantitative-proteomic-profiling-of-the-extracellular-matrix-of-pancreatic-islets-during-the-angiogenic-switch-and-insulinoma-progression
#16
Alexandra Naba, Karl R Clauser, D R Mani, Steven A Carr, Richard O Hynes
The angiogenic switch, the time at which a tumor becomes vascularized, is a critical step in tumor progression. Indeed, without blood supply, tumors will fail to grow beyond 1 mm(3) and are unlikely to disseminate. The extracellular matrix (ECM), a major component of the tumor microenvironment, is known to undergo significant changes during angiogenesis and tumor progression. However the extent of these changes remains unknown. In this study, we used quantitative proteomics to profile the composition of the ECM of pancreatic islets in a mouse model of insulinoma characterized by a precisely timed angiogenic switch...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27992417/mutations-in-the-histone-methyltransferase-gene-kmt2b-cause-complex-early-onset-dystonia
#17
Esther Meyer, Keren J Carss, Julia Rankin, John M E Nichols, Detelina Grozeva, Agnel P Joseph, Niccolo E Mencacci, Apostolos Papandreou, Joanne Ng, Serena Barral, Adeline Ngoh, Hilla Ben-Pazi, Michel A Willemsen, David Arkadir, Angela Barnicoat, Hagai Bergman, Sanjay Bhate, Amber Boys, Niklas Darin, Nicola Foulds, Nicholas Gutowski, Alison Hills, Henry Houlden, Jane A Hurst, Zvi Israel, Margaret Kaminska, Patricia Limousin, Daniel Lumsden, Shane McKee, Shibalik Misra, Shekeeb S Mohammed, Vasiliki Nakou, Joost Nicolai, Magnus Nilsson, Hardev Pall, Kathryn J Peall, Gregory B Peters, Prab Prabhakar, Miriam S Reuter, Patrick Rump, Reeval Segel, Margje Sinnema, Martin Smith, Peter Turnpenny, Susan M White, Dagmar Wieczorek, Sarah Wiethoff, Brian T Wilson, Gidon Winter, Christopher Wragg, Simon Pope, Simon J H Heales, Deborah Morrogh, Alan Pittman, Lucinda J Carr, Belen Perez-Dueñas, Jean-Pierre Lin, Andre Reis, William A Gahl, Camilo Toro, Kailash P Bhatia, Nicholas W Wood, Erik-Jan Kamsteeg, Wui K Chong, Paul Gissen, Maya Topf, Russell C Dale, Jonathan R Chubb, F Lucy Raymond, Manju A Kurian
Histone lysine methylation, mediated by mixed-lineage leukemia (MLL) proteins, is now known to be critical in the regulation of gene expression, genomic stability, cell cycle and nuclear architecture. Despite MLL proteins being postulated as essential for normal development, little is known about the specific functions of the different MLL lysine methyltransferases. Here we report heterozygous variants in the gene KMT2B (also known as MLL4) in 27 unrelated individuals with a complex progressive childhood-onset dystonia, often associated with a typical facial appearance and characteristic brain magnetic resonance imaging findings...
February 2017: Nature Genetics
https://www.readbyqxmd.com/read/27934002/reversible-transformation-of-pt-nanoparticles-into-single-atoms-inside-high-silica-chabazite-zeolite
#18
Manuel Moliner, Jadeene E Gabay, Chris E Kliewer, Robert T Carr, Javier Guzman, Gary L Casty, Pedro Serna, Avelino Corma
We report the encapsulation of platinum species in highly siliceous chabazite (CHA) crystallized in the presence of N,N,N-trimethyl-1-adamantammonium and a thiol-stabilized Pt complex. When compared to Pt/SiO2 or Pt-containing Al-rich zeolites, the materials in this work show enhanced stability toward metal sintering in a variety of industrial conditions, including H2, O2, and H2O. Remarkably, temperatures in the range 650-750 °C can be reached without significant sintering of the noble metal. Detailed structural determinations by X-ray absorption spectroscopy and aberration-corrected high-angle annular dark-field scanning transmission electron microscopy demonstrate subtle control of the supported metal structures from ∼1 nm nanoparticles to site-isolated single Pt atoms via reversible interconversion of one species into another in reducing and oxidizing atmospheres...
December 7, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27907062/sepsis-prevalence-and-outcome-on-the-general-wards-and-emergency-departments-in-wales-results-of-a-multi-centre-observational-point-prevalence-study
#19
Tamas Szakmany, Robert M Lundin, Ben Sharif, Gemma Ellis, Paul Morgan, Maja Kopczynska, Amrit Dhadda, Charlotte Mann, Danielle Donoghue, Sarah Rollason, Emma Brownlow, Francesca Hill, Grace Carr, Hannah Turley, James Hassall, James Lloyd, Llywela Davies, Michael Atkinson, Molly Jones, Nerys Jones, Rhodri Martin, Yousef Ibrahim, Judith E Hall
Data on sepsis prevalence on the general wards is lacking on the UK and in the developed world. We conducted a multicentre, prospective, observational study of the prevalence of patients with sepsis or severe sepsis on the general wards and Emergency Departments (ED) in Wales. During the 24-hour study period all patients with NEWS≥3 were screened for presence of 2 or more SIRS criteria. To be eligible for inclusion, patients had to have a high clinical suspicion of an infection, together with a systemic inflammatory response (sepsis) and evidence of acute organ dysfunction and/or shock (severe sepsis)...
2016: PloS One
https://www.readbyqxmd.com/read/27875209/jacobi-fiber-surfaces-for-bivariate-reeb-space-computation
#20
Julien Tierny, Hamish Carr
This paper presents an efficient algorithm for the computation of the Reeb space of an input bivariate piecewise linear scalar function f defined on a tetrahedral mesh. By extending and generalizing algorithmic concepts from the univariate case to the bivariate one, we report the first practical, output-sensitive algorithm for the exact computation of such a Reeb space. The algorithm starts by identifying the Jacobi set of f, the bivariate analogs of critical points in the univariate case. Next, the Reeb space is computed by segmenting the input mesh along the new notion of Jacobi Fiber Surfaces, the bivariate analog of critical contours in the univariate case...
January 2017: IEEE Transactions on Visualization and Computer Graphics
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