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Michael Reidy, Shailesh Kumar, D Eric Anderson, Daniel C Masison
The Hsp90 chaperone is regulated by many co-chaperones that tune its activities, but how they act to coordinate various steps in the reaction cycle is unclear. The primary role of Saccharomyces cerevisiae Hsp70/Hsp90 co-chaperone Sti1 (Hop in mammals) is to bridge Hsp70 and Hsp90 to facilitate client transfer. Sti1 is not essential, so Hsp90 can interact with Hsp70 in vivo without Sti1. Nevertheless, many Hsp90 mutations make Sti1 necessary for viability, which points to sites of Hsp90 as important for Hsp70 interaction...
June 21, 2018: Genetics
Md Yuzaiful Md Yusof, Antonios Psarras, Yasser M El-Sherbiny, Elizabeth M A Hensor, Katherine Dutton, Sabih Ul-Hassan, Ahmed S Zayat, Mohammad Shalbaf, Adewonuola Alase, Miriam Wittmann, Paul Emery, Edward M Vital
OBJECTIVE: To evaluate clinical, interferon and imaging predictors of progression from 'At Risk' to autoimmune connective tissue diseases (AI-CTDs). METHODS: A prospective observational study was conducted in At-Risk of AI-CTD (defined as antinuclear antibody (ANA) positive; ≤1 clinical systemic lupus erythematosus (SLE) criterion; symptom duration <12 months and treatment-naïve). Bloods and skin biopsy (non-lesional) were analysed for two interferon-stimulated gene expression scores previously described (IFN-Score-A and IFN-Score-B)...
June 21, 2018: Annals of the Rheumatic Diseases
Xiaojian Zhou, Xiaozhu Wu, Tongjian Li, Mingliang Jia, Xinshen Liu, Yulan Zou, Zixia Liu, Feng Wen
Auxin response factors (ARFs) are one type of essential family of transcription factors that bind with auxin response elements (AuxRE), and play vital roles in variety of plant development and physiological processes. Brachypodium distachyon, related to the major cereal grain species, were recently developed to be a good model organism for functional genomics research. So far, genome-wide overview of the ARF gene family in B. distachyon was not available. Here, a systemic analysis of ARF gene family members in B...
June 20, 2018: Functional & Integrative Genomics
Federica De Giacomi, Misbah Baqir, Christian W Cox, Teng Moua, Eric L Matteson, Jay H Ryu
BACKGROUND: Spontaneous pneumomediastinum (SP) is an uncommon disorder but has been described in cases with connective tissue diseases (CTDs), most commonly dermatomyositis and polymyositis. We aimed to explore this relationship by analyzing the characteristics of CTD patients with SP. METHODS: Using a computer-assisted search, we identified 25 patients with CTD and SP evaluated between January 1997 and December 2016 at our institution. Clinicoradiologic characteristics, treatment, and outcomes were extracted and chest computed tomography studies analyzed...
June 18, 2018: Journal of Clinical Rheumatology: Practical Reports on Rheumatic & Musculoskeletal Diseases
Wen Zhang, Xiang Yue, Weiran Lin, Wenjian Wu, Ruoqi Liu, Feng Huang, Feng Liu
BACKGROUND: Drug-disease associations provide important information for the drug discovery. Wet experiments that identify drug-disease associations are time-consuming and expensive. However, many drug-disease associations are still unobserved or unknown. The development of computational methods for predicting unobserved drug-disease associations is an important and urgent task. RESULTS: In this paper, we proposed a similarity constrained matrix factorization method for the drug-disease association prediction (SCMFDD), which makes use of known drug-disease associations, drug features and disease semantic information...
June 19, 2018: BMC Bioinformatics
Lucía Ramos-Alonso, Antonia María Romero, Maria Àngel Soler, Ana Perea-García, Paula Alepuz, Sergi Puig, María Teresa Martínez Pastor
In response to iron deficiency, the budding yeast Saccharomyces cerevisiae undergoes a metabolic remodeling in order to optimize iron utilization. The tandem zinc finger (TZF)-containing protein Cth2 plays a critical role in this adaptation by binding and promoting the degradation of multiple mRNAs that contain AU-rich elements (AREs). Here, we demonstrate that Cth2 also functions as a translational repressor of its target mRNAs. By complementary approaches, we demonstrate that Cth2 protein inhibits the translation of SDH4, which encodes a subunit of succinate dehydrogenase, and CTH2 mRNAs in response to iron depletion...
June 18, 2018: PLoS Genetics
Gianni Belcaro, Mark Dugall, Roberto Cotellese, Beatrice Feragalli, Ettore Cianchetti, Maria R Cesarone
BACKGROUND: Post-mastectomy lymphedema is one of the most significant, non-life-threatening complications following breast cancer surgery and radiotherapy. Post-mastectomy post-radiotherapy (PMPR) lymphedema is related to damages to lymphatics and/or veins during/after axillary surgery and radiotherapy. The management of this condition is very challenging; the comprehensive decongestive therapy (CTD), which combines physiotherapy, self-management, and hygiene, and is currently considered the standard management (SM)...
June 2018: Minerva Chirurgica
Itziar Serna Martin, Narin Hengrung, Max Renner, Jane Sharps, Mónica Martínez-Alonso, Simonas Masiulis, Jonathan M Grimes, Ervin Fodor
Influenza virus RNA polymerase (FluPol), a heterotrimer composed of PB1, PB2, and PA subunits (P3 in influenza C), performs both transcription and replication of the viral RNA genome. For transcription, FluPol interacts with the C-terminal domain (CTD) of RNA polymerase II (Pol II), which enables FluPol to snatch capped RNA primers from nascent host RNAs. Here, we describe the co-crystal structure of influenza C virus polymerase (FluPolC ) bound to a Ser5-phosphorylated CTD (pS5 -CTD) peptide. The position of the CTD-binding site at the interface of PB1, P3, and the flexible PB2 C-terminal domains suggests that CTD binding stabilizes the transcription-competent conformation of FluPol...
May 25, 2018: Molecular Cell
Theerawat Kumutpongpanich, Weerapat Owattanapanich, Jantima Tanboon, Ichizo Nishino, Kanokwan Boonyapisit
Sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance is a rare subacute adult-onset myopathy. Without appropriate treatment, the prognosis is unfavorable and can be fatal. Various efficacious treatment options have been reported. High dose melphalan followed by autologous stem cell transplantation is the most used option with favorable outcome. Nevertheless, potentially safer alternative regimens await exploration. Here, we report the case of sporadic late-onset nemaline myopathy with monoclonal gammopathy of undetermined significance in a 33-year-old man with significant clinical improvement and complete remission of monoclonal gammopathy after 5 cycles of cyclophosphamide, thalidomide, and dexamethasone regimen...
May 16, 2018: Neuromuscular Disorders: NMD
Madushi Wanaguru, David J Barry, Donald J Benton, Nicola J O'Reilly, Kate N Bishop
The murine leukaemia virus (MLV) Gag cleavage product, p12, is essential for both early and late steps in viral replication. The N-terminal domain of p12 binds directly to capsid (CA) and stabilises the mature viral core, whereas defects in the C-terminal domain (CTD) of p12 can be rescued by addition of heterologous chromatin binding sequences (CBSs). We and others hypothesised that p12 tethers the pre-integration complex (PIC) to host chromatin ready for integration. Using confocal microscopy, we have observed for the first time that CA localises to mitotic chromatin in infected cells in a p12-dependent manner...
June 15, 2018: PLoS Pathogens
Alison B Callahan, Ashley A Campbell, Susel Oropesa, Aryeh Baraban, Michael Kazim
PURPOSE: Diagnosing thyroid eye disease-compressive optic neuropathy (TED-CON) is challenging, particularly in cases lacking a relative afferent pupillary defect. Large case series of TED-CON patients and accessible diagnostic tools are lacking in the current literature. This study aims to create a mathematical formula that accurately predicts the presence or absence of CON based on the most salient clinical measures of optic neuropathy. METHODS: A retrospective case series compares 108 patients (216 orbits) with either unilateral or bilateral TED-CON and 41 age-matched patients (82 orbits) with noncompressive TED...
June 13, 2018: Ophthalmic Plastic and Reconstructive Surgery
Rajveer Joea, Sarah J Strube, Todd K Zynda
Spontaneous coronary artery dissection (SCAD) is a variant of acute coronary syndrome (ACS) that is poorly understood. SCAD has been linked to fibromuscular dysplasia (FMD), connective tissue disease (CTD), pregnancy and hormonal imbalance, systemic inflammatory conditions (e.g. IBD, vasculitis), and coronary artery vasospasm rather than traditional cardiac risk factors. Symptomology generally accompanying SCAD is indistinguishable from ACS making the timely recognition and diagnosis vital for prompt treatment...
June 2018: Cardiology Research
Yong-Zhi Zhai, Xin Chen, Xin Liu, Zhi-Qiang Zhang, Hong-Ju Xiao, Gang Liu
Fever of unknown origin (FUO) is a frequently observed phenomenon in clinical practice. The present study was aimed to investigate potential causes of FUO, thereby improving clinical diagnosis of this disorder.In this retrospective study, clinical data were collected from 215 patients who were diagnosed with FUO between January 2009 and December 2010, and an 18 to 36 months follow-up visit was also performed for these patients.Among these FUO cases, the most common causes of the disease were infectious diseases (IDs) (42...
June 2018: Medicine (Baltimore)
Tamara Cibic, Cinzia Comici, Claus Falconi, Daniela Fornasaro, Ana Karuza, Marina Lipizer
Biological, hydrological and chemical data were acquired at monthly intervals from March 2006 to February 2007, at the Long-Term Ecological Research site C1 in the Gulf of Trieste, in the northernmost part of the Adriatic Sea. The biological dataset comprises total chl a and phaeopigment concentrations, and the distinction of the total phytoplankton biomass into three photoautotrophic community fractions, i.e. cyanobacteria, nano- and microphytoplankton, collected at discrete depths. Hydrological data encompass the thermohaline properties of the water column (temperature and salinity profiles from CTD casts)...
August 2018: Data in Brief
Jin Wang, Yan Zhao, Hua Jin, Jing Tao, Luquan Cao, Yan Cai
OBJECTIVE: To assess the value of single nucleotide polymorphism array (SNP array) for the study of fetuses with conotruncal defects (CTD) detected by echocardiography. METHODS: SNP array was carried out on 75 fetuses with sonographically detected CTD but a normal karyotype. The results were analyzed with ChAS software. RESULTS: Pathogenic CNVs were detected in 7 (9.3%) of all cases. Variant of uncertain significance (VOUS) was detected in 2 (2...
June 10, 2018: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
Prabina K Meher, Tanmaya K Sahu, Jyotilipsa Mohanty, Shachi Gahoi, Supriya Purru, Monendra Grover, Atmakuri R Rao
As inorganic nitrogen compounds are essential for basic building blocks of life (e.g., nucleotides and amino acids), the role of biological nitrogen-fixation (BNF) is indispensible. All nitrogen fixing microbes rely on the same nitrogenase enzyme for nitrogen reduction, which is in fact an enzyme complex consists of as many as 20 genes. However, the occurrence of six genes viz., nifB, nifD, nifE, nifH, nifK , and nifN has been proposed to be essential for a functional nitrogenase enzyme. Therefore, identification of these genes is important to understand the mechanism of BNF as well as to explore the possibilities for improving BNF from agricultural sustainability point of view...
2018: Frontiers in Microbiology
Dinesh Khanna, Donald P Tashkin, Christopher P Denton, Martin W Lubell, Cristina Vazquez-Mateo, Stephen Wax
SSc is a rare CTD that affects multiple organ systems, resulting in substantial morbidity and mortality. Evidence of interstitial lung disease (ILD) is seen in ∼80% of patients with SSc. Currently there is no approved disease-modifying treatment for ILD and few effective treatment options are available. CYC is included in treatment guidelines, but it has limited efficacy and is associated with toxicity. MMF is becoming the most commonly used medication in clinical practice in North America and the UK, but its use is not universal...
June 8, 2018: Rheumatology
Jampa Tsedön Stelljes, Daniela Weidlich, Airat Gubaev, Dagmar Klostermeier
The topological state of DNA in vivo is regulated by topoisomerases. Gyrase is a bacterial topoisomerase that introduces negative supercoils into DNA at the expense of ATP hydrolysis. According to the strand-passage mechanism, a double-strand of the DNA substrate is cleaved, and a second double-stranded segment is passed through the gap, converting a positive DNA node into a negative node. The correct orientation of these DNA segments for strand passage is achieved by wrapping of the DNA around gyrase, which involves the C-terminal domains (CTDs) of both GyrA subunits in the A2B2 heterotetramer...
June 9, 2018: Nucleic Acids Research
Dominika Zoltowska, Jagadeesh K Kalavakunta
Cor triatriatum dexter (CTD) is an extremely rare finding (<0.01%), resulting from the persistence of the right valve of sinus venosus. Echocardiography with color Doppler is the first-line tool for diagnosis and decision making.
June 2018: Clinical Case Reports
Uddhav Timilsina, Dibya Ghimire, Laxmi Prasad Adhikari, Abhi Bhattarai, Nawneet Mishra, Madhu Rai, Ravi Chandra Dubey, Ritu Gaur
HIV-1 Maturation inhibitors (MIs) bind to the C-terminal domain of capsid protein (CA-CTD) and spacer peptide 1 (SP1) in HIV-1 Gag and inhibit the CA-SP1 cleavage by stabilizing the immature Gag. The β-turn motif, GVGGP in the HIV CA-CTD (residues 220-224) is one of the key determinants of HIV Gag assembly. In the present study, we mutated each residue of HIV-1 β-turn motif to alanine and observed complete inhibition of virus release of all mutants. This defect in virus release was rescued in the presence of maturation inhibitors; BVM and PF-46396 for P224A mutant...
June 4, 2018: Virology
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