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https://www.readbyqxmd.com/read/29323497/multi-funnel-landscape-of-the-fold-switching-protein-rfah-ctd
#1
Nathan A Bernhardt, Ulrich H E Hansmann
Proteins such as the transcription factor RfaH can change biological function by switching between distinct three-dimensional folds. RfaH regulates transcription if the C-terminal domain folds into a double helix bundle, and promotes translation when this domain assumes a β-barrel form. This fold-switch has been also observed for the isolated domain, dubbed by us RfaH-CTD, and is studied here with a variant of the RET approach recently introduced by us. We use the enhanced sampling properties of this technique to map the free energy landscape of RfaH-CTD and to propose a mechanism for the conversion process...
January 11, 2018: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29320427/peptide-mediated-liposome-fusion-the-effect-of-anchor-positioning
#2
Niek S A Crone, Dirk Minnee, Alexander Kros, Aimee L Boyle
A minimal model system for membrane fusion, comprising two complementary peptides dubbed "E" and "K" joined to a cholesterol anchor via a polyethyleneglycol spacer, has previously been developed in our group. This system promotes the fusion of large unilamellar vesicles and facilitates liposome-cell fusion both in vitro and in vivo. Whilst several aspects of the system have previously been investigated to provide an insight as to how fusion is facilitated, anchor positioning has not yet been considered. In this study, the effects of placing the anchor at either the N-terminus or in the center of the peptide are investigated using a combination of circular dichroism spectroscopy, dynamic light scattering, and fluorescence assays...
January 10, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29318562/targeting-deubiquitinases-in-cancer
#3
Joseph S Bednash, Rama K Mallampalli
The ubiquitin-proteasome system (UPS) is a complex and robust metabolic pathway that contributes to the regulation of many key cellular processes including the cell cycle, cell division, and response to external stimuli. Ubiquitin ligases, which tag proteins with ubiquitin, are opposed by deubiquitinase enzymes (DUBs). The relative activity of these enzymes allows for a dynamic balance that determines the abundance and activity of cellular proteins. Targeting the UPS in cancer has proven successful, as evidenced by use of bortezomib, a proteasome inhibitor, in multiple myeloma...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29303516/gas-phase-1h-nmr-studies-and-kinetic-modeling-of-dihydrogen-isotope-equilibration-catalyzed-by-ru-nanoparticles-under-normal-conditions-dissociative-vs-associative-exchange
#4
Hans-Heinrich Limbach, Tal Pery, Niels Rothermel, Bruno Chaudret, Torsten Gutmann, Gerd Buntkowsky
The equilibration of H2, HD and D2 between the gas phase and surface hydrides of solid organic-ligand-stabilized Ru metal nanoparticles has been studied by gas phase 1H NMR spectroscopy using closed NMR tubes as batch reactors at room temperature and 800 mbar. When two different nanoparticle systems, Ru/PVP (PVP ≡ polyvinylpyrrolidone) and Ru/HDA (HDA ≡ hexadecylamine) were exposed to D2 gas, only the release of HD from the hydride containing surface could be detected in the initial stages of the reaction, but no H2...
January 5, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29300720/prevalence-and-trends-in-prepregnancy-normal-weight-48-states-new-york-city-and-district-of-columbia-2011-2015
#5
Nicholas P Deputy, Bhanuja Dub, Andrea J Sharma
Women who enter pregnancy at a weight above or below normal weight, defined as a body mass index (BMI) of 18.5-24.9 (calculated as weight in kg/height in m2), are more likely to experience adverse pregnancy outcomes and to have infants who experience adverse health outcomes. For example, prepregnancy underweight (BMI <18.5) increases the risk for small-for-gestational-age births, whereas prepregnancy overweight (BMI 25.0-29.9) and obesity (BMI ≥30.0) increase risks for cesarean delivery, large-for-gestational-age births, and childhood obesity (1)...
January 5, 2018: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/29295994/vampnets-for-deep-learning-of-molecular-kinetics
#6
Andreas Mardt, Luca Pasquali, Hao Wu, Frank Noé
There is an increasing demand for computing the relevant structures, equilibria, and long-timescale kinetics of biomolecular processes, such as protein-drug binding, from high-throughput molecular dynamics simulations. Current methods employ transformation of simulated coordinates into structural features, dimension reduction, clustering the dimension-reduced data, and estimation of a Markov state model or related model of the interconversion rates between molecular structures. This handcrafted approach demands a substantial amount of modeling expertise, as poor decisions at any step will lead to large modeling errors...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29295552/carbon-catabolite-repression-in-filamentous-fungi
#7
REVIEW
Muhammad Adnan, Wenhui Zheng, Waqar Islam, Muhammad Arif, Yakubu Saddeeq Abubakar, Zonghua Wang, Guodong Lu
Carbon Catabolite Repression (CCR) has fascinated scientists and researchers around the globe for the past few decades. This important mechanism allows preferential utilization of an energy-efficient and readily available carbon source over relatively less easily accessible carbon sources. This mechanism helps microorganisms to obtain maximum amount of glucose in order to keep pace with their metabolism. Microorganisms assimilate glucose and highly favorable sugars before switching to less-favored sources of carbon such as organic acids and alcohols...
December 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29288197/recruitment-and-allosteric-stimulation-of-a-histone-deubiquitinating-enzyme-during-heterochromatin-assembly
#8
Alexis Zukowksi, Nouf Omar Al-Afaleq, Emily D Duncan, Tingting Yao, Aaron M Johnson
Heterochromatin formation in budding yeast is regulated by the silent information regulator (SIR) complex. The SIR complex comprises the NAD-dependent deacetylase Sir2, the scaffolding protein Sir4, and the nucleosome-binding protein Sir3. Transcriptionally active regions present a challenge to SIR complex-mediated de novo heterochromatic silencing due to the presence of antagonistic histone PTMs, including acetylation and methylation. Methylation of histone H3K4 and H3K79 are dependent on mono-ubiquitination of histone H2B (H2B-Ub)...
December 29, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29286692/three-dimensional-localized-delocalized-anderson-transition-in-the-time-domain
#9
Dominique Delande, Luis Morales-Molina, Krzysztof Sacha
Systems which can spontaneously reveal periodic evolution are dubbed time crystals. This is in analogy with space crystals that display periodic behavior in configuration space. While space crystals are modeled with the help of space periodic potentials, crystalline phenomena in time can be modeled by periodically driven systems. Disorder in the periodic driving can lead to Anderson localization in time: the probability for detecting a system at a fixed point of configuration space becomes exponentially localized around a certain moment in time...
December 8, 2017: Physical Review Letters
https://www.readbyqxmd.com/read/29284755/lamost-telescope-reveals-that-neptunian-cousins-of-hot-jupiters-are-mostly-single-offspring-of-stars-that-are-rich-in-heavy-elements
#10
Subo Dong, Ji-Wei Xie, Ji-Lin Zhou, Zheng Zheng, Ali Luo
We discover a population of short-period, Neptune-size planets sharing key similarities with hot Jupiters: both populations are preferentially hosted by metal-rich stars, and both are preferentially found in Kepler systems with single-transiting planets. We use accurate Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) Data Release 4 (DR4) stellar parameters for main-sequence stars to study the distributions of short-period [Formula: see text] Kepler planets as a function of host star metallicity...
December 28, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29280960/metagomics-a-web-based-tool-for-peptide-centric-functional-and-taxonomic-analysis-of-metaproteomics-data
#11
Michael Riffle, Damon H May, Emma Timmins-Schiffman, Molly P Mikan, Daniel Jaschob, William Stafford Noble, Brook L Nunn
Metaproteomics is the characterization of all proteins being expressed by a community of organisms in a complex biological sample at a single point in time. Applications of metaproteomics range from the comparative analysis of environmental samples (such as ocean water and soil) to microbiome data from multicellular organisms (such as the human gut). Metaproteomics research is often focused on the quantitative functional makeup of the metaproteome and which organisms are making those proteins. That is: What are the functions of the currently expressed proteins? How much of the metaproteome is associated with those functions? And, which microorganisms are expressing the proteins that perform those functions? However, traditional protein-centric functional analysis is greatly complicated by the large size, redundancy, and lack of biological annotations for the protein sequences in the database used to search the data...
December 27, 2017: Proteomes
https://www.readbyqxmd.com/read/29258884/drug-toxicity-profiling-of-a-saccharomyces-cerevisiae-deubiquitinase-deletion-panel-shows-that-acetaminophen-mimics-tyrosine
#12
Angelina Huseinovic, Marc van Dijk, Nico P E Vermeulen, Fred van Leeuwen, Jan M Kooter, J Chris Vos
Post-translational protein modification by addition or removal of the small polypeptide ubiquitin is involved in a range of critical cellular processes, like proteasomal protein degradation, DNA repair, gene expression, internalization of membrane proteins, and drug sensitivity. We recently identified genes important for acetaminophen (APAP) toxicity in a comprehensive screen and our findings suggested that a small set of yeast strains carrying deletions of ubiquitin-related genes can be informative for drug toxicity profiling...
December 16, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29251738/nm23-proteins-innocent-bystanders-or-local-energy-boosters-for-cftr
#13
Richmond Muimo, Hani Mm Alothaid, Anil Mehta
NM23 proteins NDPK-A and -B bind to the cystic fibrosis (CF) protein CFTR in different ways from kinases such as PKA, CK2 and AMPK or linkers to cell calcium such as calmodulin and annexins. NDPK-A (not -B) interacts with CFTR through reciprocal AMPK binding/control, whereas NDPK-B (not -A) binds directly to CFTR. NDPK-B can activate G proteins without ligand-receptor coupling, so perhaps NDPK-B's binding influences energy supply local to a nucleotide-binding site (NBD1) needed for CFTR to function. Curiously, CFTR (ABC-C7) is a member of the ATP-binding cassette (ABC) protein family that does not obey 'clan rules'; CFTR channels anions and is not a pump, regulates disparate processes, is itself regulated by multiple means and is so pleiotropic that it acts as a hub that orchestrates calcium signaling through its consorts such as calmodulin/annexins...
December 18, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/29250433/insights-into-origin-and-evolution-of-%C3%AE-proteobacterial-gene-transfer-agents
#14
Migun Shakya, Shannon M Soucy, Olga Zhaxybayeva
Several bacterial and archaeal lineages produce nanostructures that morphologically resemble small tailed viruses, but, unlike most viruses, contain apparently random pieces of the host genome. Since these elements can deliver the packaged DNA to other cells, they were dubbed gene transfer agents (GTAs). Because many genes involved in GTA production have viral homologs, it has been hypothesized that the GTA ancestor was a virus. Whether GTAs represent an atypical virus, a defective virus, or a virus co-opted by the prokaryotes for some function, remains to be elucidated...
July 2017: Virus Evolution
https://www.readbyqxmd.com/read/29247997/the-nlrc4-inflammasome
#15
REVIEW
Joseph A Duncan, Scott W Canna
15 years ago, the fundamental biology of an inflammatory signaling complex eventually dubbed "the inflammasome" began to unravel in chronologic parallel with the discovery that many inflammatory diseases were associated with its hyperactivity. Though the genetic origins of Familial Mediterranean Fever (FMF, caused my mutations in MEFV) were discovered first, it would take nearly two decades before the mechanistic connections to a PYRIN inflammasome were made. In the interim, the intensive study of the NLRP3 inflammasome, and the diseases associated with its hyperactivation, have largely dictated the paradigm of inflammasome composition and function...
January 2018: Immunological Reviews
https://www.readbyqxmd.com/read/29234907/rheotropism-of-the-dowser-texture
#16
Pawel Pieranski, Jean-Pierre Hulin, Maria Helena Godinho
In spite of its metastability, the pseudo-planar texture of a nematic layer confined between surfaces with homeotropic anchoring can be preserved indefinitely in certain conditions. The pseudo-planar texture, dubbed "the dowser texture", is degenerated and therefore sensitive to perturbations. It has been shown recently that the dowser texture is cuneitropic, that is to say, has a tendency to follow thickness gradients. Here, we point out that the dowser texture is also rheotropic or, in other words, has a weathercock behavior: it tends to follow the direction of Poiseuille flows...
December 14, 2017: European Physical Journal. E, Soft Matter
https://www.readbyqxmd.com/read/29230188/control-of-rest-activity-by-a-dopaminergic-ultradian-oscillator-and-the-circadian-clock
#17
REVIEW
Clément Bourguignon, Kai-Florian Storch
There is long-standing evidence for rhythms in locomotor activity, as well as various other aspects of physiology, with periods substantially shorter than 24 h in organisms ranging from fruit flies to humans. These ultradian oscillations, whose periods frequently fall between 2 and 6 h, are normally well integrated with circadian rhythms; however, they often lack the period stability and expression robustness of the latter. An adaptive advantage of ultradian rhythms has been clearly demonstrated for the common vole, suggesting that they may have evolved to confer social synchrony...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/29223882/recurrent-renal-cancer-in-birt-hogg-dub%C3%A3-syndrome-a-case-report
#18
Hammad Ather, Nida Zahid
INTRODUCTION: Birt-Hogg-Dubé syndrome (BHDS) is a rare autosomal dominant disease. It is caused by constitutional mutations in the FLCN gene. Since BHDS is a rare syndrome therefore it is unknown to many physicians. However, it is important to identify this rare syndrome at early stages because incidence of renal cancer in BHD patients is very high and its detection at early stages can prevent its metastasis. Hence, we want to present a case of BHDS and draw the attention of the treating physician to this rare inherited disorder and discuss its appropriate diagnosis and management...
November 28, 2017: International Journal of Surgery Case Reports
https://www.readbyqxmd.com/read/29216364/energetic-funnel-facilitates-facilitated-diffusion
#19
Massimo Cencini, Simone Pigolotti
Transcription factors (TFs) are able to associate to their binding sites on DNA faster than the physical limit posed by diffusion. Such high association rates can be achieved by alternating between three-dimensional diffusion and one-dimensional sliding along the DNA chain, a mechanism-dubbed facilitated diffusion. By studying a collection of TF binding sites of Escherichia coli from the RegulonDB database and of Bacillus subtilis from DBTBS, we reveal a funnel in the binding energy landscape around the target sequences...
December 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29203593/loss-of-p53-compensates-osteopenia-in-murine-mysm1-deficiency
#20
Melanie Haffner-Luntzer, Anna Kovtun, Verena Fischer, Katja Prystaz, Adelheid Hainzl, Carsten M Kroeger, Ioanna Krikki, Titus J Brinker, Anita Ignatius, Martina Gatzka
Histone modifications critically contribute to the epigenetic orchestration of bone homeostasis-in part, by modifying the access of transcription factors to specific genes involved in the osteogenic differentiation process of bone marrow mesenchymal stem cells (MSCs) and osteoblasts. Based on our previous finding that histone H2A deubiquitinase 2A-DUB/Mysm1 interacts with the p53 axis in hematopoiesis and tissue development, we analyzed the molecular basis of the skeletal phenotype of Mysm1-deficient mice and dissected the underlying p53-dependent and -independent mechanisms...
December 4, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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