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https://www.readbyqxmd.com/read/29234907/rheotropism-of-the-dowser-texture
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/29201911/transmissible-gastroenteritis-virus-papain-like-protease-1-antagonizes-production-of-interferon-%C3%AE-through-its-deubiquitinase-activity
#6
Xiaoliang Hu, Jin Tian, Hongtao Kang, Dongchun Guo, Jiasen Liu, Dafei Liu, Qian Jiang, Zhijie Li, Juanjuan Qu, Liandong Qu
Coronaviruses (CoVs), such as human coronavirus NL63 (HCoV-NL63), severe acute respiratory syndrome CoV (SARS-CoV), murine hepatitis virus (MHV), porcine epidemic diarrhea virus (PEDV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), encode papain-like (PL) proteases that inhibit Sendai virus- (SeV-) induced interferon (IFN-β) production. Recently, the crystal structure of transmissible gastroenteritis virus (TGEV) PL1 has been solved, which was similar to that of SARS-CoV PL2pro, which may antagonize host innate immunity...
2017: BioMed Research International
https://www.readbyqxmd.com/read/29200206/discovery-and-characterization-of-highly-potent-and-selective-allosteric-usp7-inhibitors
#7
Gerald Gavory, Colin R O'Dowd, Matthew D Helm, Jakub Flasz, Elias Arkoudis, Anthony Dossang, Caroline Hughes, Eamon Cassidy, Keeva McClelland, Ewa Odrzywol, Natalie Page, Oliver Barker, Hugues Miel, Timothy Harrison
Given the importance of ubiquitin-specific protease 7 (USP7) in oncogenic pathways, identification of USP7 inhibitors has attracted considerable interest. Despite substantial efforts, however, the development of validated deubiquitinase (DUB) inhibitors that exhibit drug-like properties and a well-defined mechanism of action has proven particularly challenging. In this article, we describe the identification, optimization and detailed characterization of highly potent (IC50 < 10 nM), selective USP7 inhibitors together with their less active, enantiomeric counterparts...
December 4, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/29185979/with-direct-contracting-boeing-cuts-out-the-middleman
#8
Joseph Burns
The company has more than 15,000 employees - or about a third of the eligible employees in those four locations - enrolled in direct contracts. Boeing has dubbed the direct contracts its Preferred Partnership health plan. Should insurers worry that other large companies will cut them out?
November 2017: Managed Care
https://www.readbyqxmd.com/read/29185165/immune-parameters-associated-with-mortality-in-the-elderly-are-context-dependent-lessons-from-sweden-holland-and-belgium
#9
Graham Pawelec
The pioneering Swedish OCTO/NONA-Immune longitudinal studies led by Anders Wikby in Jönköping in the 1990s established a cluster of simple baseline immune parameters associated with excess mortality in 85 year-old non-institutionalized individuals over 2, 4 and 6-year follow-up. We dubbed this cluster the "Immune Risk Profile" (IRP) consisting of poor proliferative responses of peripheral blood mononuclear cells to T cell mitogens, accumulations of CD8+ CD28- T-cells resulting in an inverted CD4:8 ratio, decreased amounts of B-cells, and seropositivity for Cytomegalovirus (CMV)...
November 28, 2017: Biogerontology
https://www.readbyqxmd.com/read/29177816/frames-of-reference-and-antecedentless-anaphora-in-spanish-conversation
#10
Sarah E Blackwell
This study examines native Spanish speakers' use of anaphoric pronouns and null subjects in conversational discourse in the absence of coreferential antecedents. It also considers the adequacy of Gundel et al.'s proposal  (Language 69(2):274-307, 1993) that the cognitive status "in focus" corresponds with speakers' use of minimal referring expressions (i.e., unstressed pronouns and zeros). Analysis of naturally occurring Spanish conversation shows how the felicitous use and interpretation of non-canonical (antecedentless) anaphoric pronouns and null subjects are possible due to the activation of underlying cognitive frames that are shared by the interlocutors...
November 25, 2017: Journal of Psycholinguistic Research
https://www.readbyqxmd.com/read/29170373/caldera-resurgence-driven-by-magma-viscosity-contrasts
#11
Federico Galetto, Valerio Acocella, Luca Caricchi
Calderas are impressive volcanic depressions commonly produced by major eruptions. Equally impressive is the uplift of the caldera floor that may follow, dubbed caldera resurgence, resulting from magma accumulation and accompanied by minor eruptions. Why magma accumulates, driving resurgence instead of feeding large eruptions, is one of the least understood processes in volcanology. Here we use thermal and experimental models to define the conditions promoting resurgence. Thermal modelling suggests that a magma reservoir develops a growing transition zone with relatively low viscosity contrast with respect to any newly injected magma...
November 24, 2017: Nature Communications
https://www.readbyqxmd.com/read/29167334/flow-virometry-a-powerful-tool-to-functionally-characterize-viruses
#12
Roger Lippé
For several decades, flow cytometry has been a common approach to analyze cells and sort them to near purity. It enables one to probe inner cellular molecules, surface receptors or infected cells. However, the analysis of smaller entities such as viruses and exocytic vesicles has been more difficult but is becoming mainstream. This has in part been due to the development of new instrumentation with resolutions below conventional cytometers. It is also attributed to the several means to fluorescently label viruses, hence enabling them to stand out from the similarly sized background noise...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29164995/novel-polyubiquitin-imaging-system-polyub-fc-reveals-that-k33-linked-polyubiquitin-is-recruited-by-sqstm1-p62
#13
Yoichi Nibe, Shigeru Oshima, Masanori Kobayashi, Chiaki Maeyashiki, Yu Matsuzawa, Kana Otsubo, Hiroki Matsuda, Emi Aonuma, Yasuhiro Nemoto, Takashi Nagaishi, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Shinichiro Nakada, Mamoru Watanabe
Ubiquitin chains are formed with 8 structurally and functionally distinct polymers. However, the functions of each polyubiquitin remain poorly understood. We developed a polyubiquitin-mediated fluorescence complementation (PolyUb-FC) assay using Kusabira Green (KG) as a split fluorescent protein. The PolyUb-FC assay has the advantage that monoubiquitination is nonfluorescent and chain-specific poly-ubiquitination can be directly visualized in living cells without using antibodies. We applied the PolyUb-FC assay to examine K33-linked polyubiquitin...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29163669/current-status-and-perspectives-of-genome-editing-technology-for-microalgae
#14
REVIEW
Seungjib Jeon, Jong-Min Lim, Hyung-Gwan Lee, Sung-Eun Shin, Nam Kyu Kang, Youn-Il Park, Hee-Mock Oh, Won-Joong Jeong, Byeong-Ryool Jeong, Yong Keun Chang
Genome editing techniques are critical for manipulating genes not only to investigate their functions in biology but also to improve traits for genetic engineering in biotechnology. Genome editing has been greatly facilitated by engineered nucleases, dubbed molecular scissors, including zinc-finger nuclease (ZFN), TAL effector endonuclease (TALEN) and clustered regularly interspaced palindromic sequences (CRISPR)/Cas9. In particular, CRISPR/Cas9 has revolutionized genome editing fields with its simplicity, efficiency and accuracy compared to previous nucleases...
2017: Biotechnology for Biofuels
https://www.readbyqxmd.com/read/29142505/targeting-deubiquitinating-enzymes-in-cancer-stem-cells
#15
REVIEW
Hu Lei, Huizhuang Shan, Yingli Wu
Cancer stem cells (CSCs) are rare but accounted for tumor initiation, progression, metastasis, relapse and therapeutic resistance. Ubiquitination and deubiquitination of stemness-related proteins are essential for CSC maintenance and differentiation, even leading to execute various stem cell fate choices. Deubiquitinating enzymes (DUBs), specifically disassembling ubiquitin chains, are important to maintain the balance between ubiquitination and deubiquitination. In this review, we have focused on the DUBs regulation of stem cell fate determination...
2017: Cancer Cell International
https://www.readbyqxmd.com/read/29131570/identification-and-characterisation-of-dual-inhibitors-of-the-usp25-28-deubiquitinating-enzyme-subfamily
#16
Jonathan D Wrigley, Gerald Gavory, Iain Simpson, Marian Preston, Helen Plant, Jenna Bradley, Anne U Goeppert, Ewelina Rozycka, Gareth Davies, Jarrod Walsh, Andrea Valentine, Keeva McClelland, Krzysztofa Ewa Odrzywol, Jonathan Renshaw, Joanna Boros, Jonathan Tart, Lindsey Leach, Thorsten Nowak, Richard A Ward, Timothy Harrison, David M Andrews
The Ubiquitin Proteasome System is widely postulated to be a new and important field of drug discovery for the future, with the Ubiquitin Specific Proteases (USP) representing one of the more attractive target classes within the area. Many USPs have been linked to critical axes for therapeutic intervention, and the finding that USP28 is required for c-Myc stability suggests that USP28 inhibition may represent a novel approach to target this so far undruggable oncogene. Here we describe the discovery of the first reported inhibitors of USP28, which we demonstrate are able to bind to and inhibit USP28, and whilst displaying a dual activity against the closest homologue USP25, these inhibitors show a high degree of selectivity over other deubiquitinases...
November 13, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/29126920/the-fentanyl-epidemic-in-canada-some-cautionary-observations-focusing-on-opioid-related-mortality
#17
Benedikt Fischer, Lenka Vojtila, Jürgen Rehm
In Canada, opioid-related overdose mortality has steeply increased in recent years; as a substantial number of opioid-related deaths are related to 'fentanyl' products, this phenomenon has widely been dubbed the 'fentanyl epidemic', also implying that these deaths are largely caused by clandestinely 'illicit fentanyl' products. We examined numbers and rates of opioid- and fentanyl-related deaths in six pan-Canadian provinces with respective (coroner-based) data available from 2010 to 2016. While fentanyl-related deaths are clearly increasing from relatively low levels in all provinces, those increases are strongest in the two Western provinces (e...
November 7, 2017: Preventive Medicine
https://www.readbyqxmd.com/read/29126218/libra-wa-a-web-application-for-ligand-binding-site-detection-and-protein-function-recognition
#18
Daniele Toti, Viet Hung Le, Valentina Tortosa, Valentina Brandi, Fabio Polticelli
Summary: Recently, LIBRA, a tool for active/ligand binding site prediction, was described. LIBRA's effectiveness was comparable to similar state-of-the-art tools; however, its scoring scheme, output presentation, dependence on local resources and overall convenience were amenable to improvements. To solve these issues, LIBRA-WA, a web application based on an improved LIBRA engine, has been developed, featuring a novel scoring scheme consistently improving LIBRA's performance, and a refined algorithm that can identify binding sites hosted at the interface between different subunits...
November 6, 2017: Bioinformatics
https://www.readbyqxmd.com/read/29117247/a-mobile-loop-near-the-active-site-acts-as-a-switch-between-the-dual-activities-of-a-viral-protease-deubiquitinase
#19
Isabelle Jupin, Maya Ayach, Lucile Jomat, Sonia Fieulaine, Stéphane Bressanelli
The positive-strand RNA virus Turnip yellow mosaic virus (TYMV) encodes an ovarian tumor (OTU)-like protease/deubiquitinase (PRO/DUB) protein domain involved both in proteolytic processing of the viral polyprotein through its PRO activity, and in removal of ubiquitin chains from ubiquitylated substrates through its DUB activity. Here, the crystal structures of TYMV PRO/DUB mutants and molecular dynamics simulations reveal that an idiosyncratic mobile loop participates in reversibly constricting its unusual catalytic site by adopting "open", "intermediate" or "closed" conformations...
November 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29111377/mass-spectrometry-analyses-of-normal-and-polyglutamine-expanded-ataxin-3-reveal-novel-interaction-partners-involved-in-mitochondrial-function
#20
Line V Kristensen, Felix S Oppermann, Matthias J Rauen, Karina Fog, Thorsten Schmidt, Jana Schmidt, Tina Harmuth, Rasmus Hartmann-Petersen, Kenneth Thirstrup
Deubiquitinating enzymes (DUBs) play important roles in a variety of cellular processes, including regulation of protein homeostasis. The DUB ataxin-3 is an enzyme implicated in protein quality control mechanisms. In the neurodegenerative disease spinocerebellar ataxia type 3 (SCA3), ataxin-3 contains an expanded polyglutamine (polyQ) stretch that leads to aggregation of the protein and neuronal dysfunction. Increasing the understanding of ataxin-3 protein interaction partners could help to elucidate disease mechanisms...
October 27, 2017: Neurochemistry International
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