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https://www.readbyqxmd.com/read/28934742/elevated-apoptosis-in-the-liver-of-dairy-cows-with-ketosis
#1
Xiliang Du, Liang Chen, Dan Huang, Zhicheng Peng, Chenxu Zhao, Yuming Zhang, Yiwei Zhu, Zhe Wang, Xinwei Li, Guowen Liu
BACKGROUND/AIMS: Dairy cows with ketosis are characterized by oxidative stress and hepatic damage. The aim of this study was to investigate hepatic oxidative stress and the apoptotic status of ketotic cows, as well as the underlying apoptosis pathway. METHODS: The blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase (GGT) activities and the haptoglobin (HP), serum amyloid A (SAA) and serum apoptotic cytokeratin 18 neo-epitope M30 (CK18 M30) concentrations were determined by commercially available kits and ELISA kits, respectively...
September 21, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28934589/low-dietary-protein-and-high-carbohydrate-infant-formula-affects-the-microbial-ecology-of-the-large-intestine-in-neonatal-rats
#2
Wenguang Fan, Haiwei Ren, Yingying Cao, Yonggang Wang, Guicheng Huo
The aim of this study was to investigate the effects of a low dietary protein and high carbohydrate infant formula on the large intestine of neonatal rats. A total of 24 neonatal SD rats (14d old) were randomly assigned to the low-protein, high-carbohydrate infant formula-fed group (IF group) and a human breast milk-fed group (HF group). After 7 days, we selected 6 rats at random from each group to study. No significantly different microbial colonization patterns were observed in the two groups at the phylum level...
September 21, 2017: Canadian Journal of Microbiology
https://www.readbyqxmd.com/read/28934550/structural-and-mechanical-roles-for-the-c-terminal-non-repetitive-domain-become-apparent-in-recombinant-spider-aciniform-silk
#3
Lingling Xu, Thierry Lefèvre, Kathleen E Orrell, Qing Meng, Michèle Auger, Xiang-Qin Liu, Jan K Rainey
Spider aciniform (or wrapping) silk is the toughest of the seven types of spider silks/glue due to a combination of high elasticity and strength. Like most spider silk proteins (spidroins), aciniform spidroin (AcSp1) has a large core repetitive domain flanked by relatively short N- and C-terminal non-repetitive domains (the NTD and CTD, respectively). The major ampullate silk protein (MaSp) CTD has been shown to control protein solubility and fiber formation, but the aciniform CTD function remains unknown. Here, we compare fiber mechanical properties, solution-state structuring, and fibrous state secondary structural composition and orientation relative to native aciniform silk for two AcSp1 repeat units with or without fused AcSp1- and MaSp-derived CTDs alongside three AcSp1 repeat units without a CTD...
September 21, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28934493/ubalai-is-a-monomeric-type-iie-restriction-enzyme
#4
Giedrius Sasnauskas, Giedre Tamulaitiene, Gintautas Tamulaitis, Jelena Calyševa, Migle Laime, Renata Rimšeliene, Arvydas Lubys, Virginijus Siksnys
Type II restriction endonucleases (REases) form a large and highly diverse group of enzymes. Even REases specific for a common recognition site often vary in their oligomeric structure, domain organization and DNA cleavage mechanisms. Here we report biochemical and structural characterization of the monomeric restriction endonuclease UbaLAI, specific for the pseudosymmetric DNA sequence 5'-CC/WGG-3' (where W = A/T, and '/' marks the cleavage position). We present a 1.6 Å co-crystal structure of UbaLAI N-terminal domain (UbaLAI-N) and show that it resembles the B3-family domain of EcoRII specific for the 5'-CCWGG-3' sequence...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934486/stn1-pola2-interaction-provides-a-basis-for-primase-pol-%C3%AE-stimulation-by-human-stn1
#5
Swapna Ganduri, Neal F Lue
The CST (CTC1-STN1-TEN1) complex mediates critical functions in maintaining telomere DNA and overcoming genome-wide replication stress. A conserved biochemical function of the CST complex is its primase-Pol α (PP) stimulatory activity. In this report, we demonstrate the ability of purified human STN1 alone to promote PP activity in vitro. We show that this regulation is mediated primarily by the N-terminal OB fold of STN1, but does not require the DNA-binding activity of this domain. Rather, we observed a strong correlation between the PP-stimulatory activity of STN1 variants and their abilities to bind POLA2...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934483/the-fused-snoal_2-domain-in-the-mycobacterium-tuberculosis-sigma-factor-%C3%AF-j-modulates-promoter-recognition
#6
Kapil Goutam, Arvind K Gupta, Balasubramanian Gopal
Extra-cytoplasmic function (ECF) σ-factors are widespread in bacteria, linking environmental stimuli with changes in gene expression. These transcription factors span several phylogenetically distinct groups and are remarkably diverse in their activation and regulatory mechanisms. Here, we describe the structural and biochemical features of a Mycobacterium tuberculosis ECF factor σJ that suggests that the SnoaL_2 domain at the C-terminus can modulate the activity of this initiation factor in the absence of a cognate regulatory anti-σ factor...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934482/mechanistic-insight-into-how-multidrug-resistant-acinetobacter-baumannii-response-regulator-ader-recognizes-an-intercistronic-region
#7
Yurong Wen, Zhenlin Ouyang, Yue Yu, Xiaorong Zhou, Yingmei Pei, Bart Devreese, Paul G Higgins, Fang Zheng
AdeR-AdeS is a two-component regulatory system, which controls expression of the adeABC efflux pump involved in Acinetobacter baumannii multidrug resistance. AdeR is a response regulator consisting of an N-terminal receiver domain and a C-terminal DNA-binding-domain. AdeR binds to a direct-repeat DNA in the intercistronic region between adeR and adeABC. We demonstrate a markedly high affinity binding between unphosphorylated AdeR and DNA with a dissociation constant of 20 nM. In addition, we provide a 2.75 Å crystal structure of AdeR DNA-binding-domain complexed with the intercistronic DNA...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934476/crystal-structure-of-an-engineered-hiv-specific-recombinase-for-removal-of-integrated-proviral-dna
#8
Gretchen Meinke, Janet Karpinski, Frank Buchholz, Andrew Bohm
As part of the HIV infection cycle, viral DNA inserts into the genome of host cells such that the integrated DNA encoding the viral proteins is flanked by long terminal repeat (LTR) regions from the retrovirus. In an effort to develop novel genome editing techniques that safely excise HIV provirus from cells, Tre, an engineered version of Cre recombinase, was designed to target a 34-bp sequence within the HIV-1 LTR (loxLTR). The sequence targeted by Tre lacks the symmetry present in loxP, the natural DNA substrate for Cre...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934471/a-novel-non-canonical-pip-box-mediates-parg-interaction-with-pcna
#9
Tanja Kaufmann, Irina Grishkovskaya, Anton A Polyansky, Sebastian Kostrhon, Eva Kukolj, Karin M Olek, Sebastien Herbert, Etienne Beltzung, Karl Mechtler, Thomas Peterbauer, Josef Gotzmann, Lijuan Zhang, Markus Hartl, Bojan Zagrovic, Kareem Elsayad, Kristina Djinovic-Carugo, Dea Slade
Poly(ADP-ribose) glycohydrolase (PARG) regulates cellular poly(ADP-ribose) (PAR) levels by rapidly cleaving glycosidic bonds between ADP-ribose units. PARG interacts with proliferating cell nuclear antigen (PCNA) and is strongly recruited to DNA damage sites in a PAR- and PCNA-dependent fashion. Here we identified PARG acetylation site K409 that is essential for its interaction with PCNA, its localization within replication foci and its recruitment to DNA damage sites. We found K409 to be part of a non-canonical PIP-box within the PARG disordered regulatory region...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934391/homozygous-kidins220-loss-of-function-variants-in-fetuses-with-cerebral-ventriculomegaly-and-limb-contractures
#10
I-L Mero, H H Mørk, Y Sheng, A Blomhoff, G L Opheim, Aa Erichsen, M D Vigeland, K K Selmer
Heterozygous mutations in KIDINS220 were recently suggested a cause of spastic paraplegia, intellectual disability, nystagmus and obesity. All patients carried terminal nonsense de novo mutations that seemed to escape nonsense-mediated mRNA decay. The mechanism for pathogenicity is yet unexplained, as it seems that heterozygous loss-of-function variants of KIDINS220 are generally well tolerated. We present a consanguineous couple who experienced four pregnancy terminations due to repeated findings in the fetuses comprising enlarged cerebral ventricles and limb contractures...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934390/protein-phosphatase-1-regulates-huntingtin-exon-1-aggregation-and-toxicity
#11
Joana Branco-Santos, Federico Herrera, Gonçalo M Poças, Yolanda Pires-Afonso, Flaviano Giorgini, Pedro M Domingos, Tiago F Outeiro
Huntington's disease is neurodegenerative disorder caused by a polyglutamine expansion in the N-terminal region of the huntingtin protein (N17). Here, we analysed the relative contribution of each phosphorylatable residue in the N17 region (T3, S13 and S16) towards huntingtin exon 1 (HTTex1) oligomerization, aggregation and toxicity in human cells and Drosophila neurons. We used bimolecular fluorescence complementation to show that expression of single phosphomimic mutations completely abolished HTTex1 aggregation in human cells...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934386/expression-of-the-neuropathy-associated-mtmr2-gene-rescues-mtm1-associated-myopathy
#12
Matthieu A Raess, Belinda S Cowling, Dimitri L Bertazzi, Christine Kretz, Bruno Rinaldi, Jean-Marie Xuereb, Pascal Kessler, Norma B Romero, Bernard Payrastre, Sylvie Friant, Jocelyn Laporte
Myotubularins (MTMs) are active or dead phosphoinositides phosphatases defining a large protein family conserved through evolution and implicated in different neuromuscular diseases. Loss-of-function mutations in MTM1 cause the severe congenital myopathy called myotubular myopathy (or X-linked centronuclear myopathy) while mutations in the MTM1-related protein MTMR2 cause a recessive Charcot-Marie-Tooth peripheral neuropathy. Here we aimed to determine the functional specificity and redundancy of MTM1 and MTMR2, and to assess their abilities to compensate for a potential therapeutic strategy...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934360/pkacs-attenuate-innate-antiviral-response-by-phosphorylating-visa-and-priming-it-for-march5-mediated-degradation
#13
Bing-Ru Yan, Lu Zhou, Ming-Ming Hu, Mi Li, Heng Lin, Yan Yang, Yan-Yi Wang, Hong-Bing Shu
Sensing of viral RNA by RIG-I-like receptors initiates innate antiviral response, which is mediated by the central adaptor VISA. How the RIG-I-VISA-mediated antiviral response is terminated at the late phase of infection is enigmatic. Here we identified the protein kinase A catalytic (PKAC) subunits α and β as negative regulators of RNA virus-triggered signaling in a redundant manner. Viral infection up-regulated cellular cAMP levels and activated PKACs, which then phosphorylated VISA at T54. This phosphorylation abrogated virus-induced aggregation of VISA and primed it for K48-linked polyubiquitination and degradation by the E3 ligase MARCH5, leading to attenuation of virus-triggered induction of downstream antiviral genes...
September 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28934344/care-requirements-for-clients-who-present-after-rape-and-clients-who-presented-after-consensual-sex-as-a-minor-at-a-clinic-in-harare-zimbabwe-from-2011-to-2014
#14
Rebecca E Harrison, Linda Pearson, Michael Vere, Prosper Chonzi, Brian Tafadzwa Hove, Sharon Mabaya, Margaret Chigwamba, Juliana Nhamburo, Juliet Gura, An Vandeborne, Sandra Simons, Daphne Lagrou, Eva De Plecker, Rafael Van den Bergh
STUDY GOALS: To describe the differences between clients presenting after rape and clients who have consented to sex as a minor to an SGBV clinic in Harare, Zimbabwe, and how these differences affect their care requirements. BACKGROUND: Adolescents and adults presenting at the specialized Sexual and Gender Based Violence clinic in Harare are offered a standardised package of free medical and psychosocial care. Zimbabwe has an HIV prevalence of 14%, so prevention of HIV infection using PEP for those that present within 72 hours is a key part of the response...
2017: PloS One
https://www.readbyqxmd.com/read/28934279/spontaneous-non-canonical-assembly-of-ccmk-hexameric-components-from-%C3%AE-carboxysome-shells-of-cyanobacteria
#15
Luis F Garcia-Alles, Eric Lesniewska, Katharina Root, Nathalie Aubry, Nicolas Pocholle, Carlos I Mendoza, Eric Bourillot, Konstantin Barylyuk, Denis Pompon, Renato Zenobi, David Reguera, Gilles Truan
CcmK proteins are major constituents of icosahedral shells of β-carboxysomes, a bacterial microcompartment that plays a key role for CO2 fixation in nature. Supported by the characterization of bidimensional (2D) layers of packed CcmK hexamers in crystal and electron microscopy structures, CcmK are assumed to be the major components of icosahedral flat facets. Here, we reassessed the validity of this model by studying CcmK isoforms from Synechocystis sp. PCC6803. Native mass spectrometry studies confirmed that CcmK are hexamers in solution...
2017: PloS One
https://www.readbyqxmd.com/read/28934171/design-and-analysis-of-an-efficient-energy-algorithm-in-wireless-social-sensor-networks
#16
Naixue Xiong, Longzhen Zhang, Wei Zhang, Athanasios V Vasilakos, Muhammad Imran
Because mobile ad hoc networks have characteristics such as lack of center nodes, multi-hop routing and changeable topology, the existing checkpoint technologies for normal mobile networks cannot be applied well to mobile ad hoc networks. Considering the multi-frequency hierarchy structure of ad hoc networks, this paper proposes a hybrid checkpointing strategy which combines the techniques of synchronous checkpointing with asynchronous checkpointing, namely the checkpoints of mobile terminals in the same cluster remain synchronous, and the checkpoints in different clusters remain asynchronous...
September 21, 2017: Sensors
https://www.readbyqxmd.com/read/28934144/the-recognition-of-calmodulin-to-the-target-sequence-of-calcineurin-a-novel-binding-mode
#17
Chia-Lin Chyan, Deli Irene, Sin-Mao Lin
Calcineurin (CaN) is a Ca(2+)/calmodulin-dependent Ser/Thr protein phosphatase, which plays essential roles in many cellular and developmental processes. CaN comprises two subunits, a catalytic subunit (CaN-A, 60 kDa) and a regulatory subunit (CaN-B, 19 kDa). CaN-A tightly binds to CaN-B in the presence of minimal levels of Ca(2+), but the enzyme is inactive until activated by CaM. Upon binding to CaM, CaN then undergoes a conformational rearrangement, the auto inhibitory domain is displaced and thus allows for full activity...
September 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28934133/understanding-the-mechanism-of-translocation-of-adenylate-cyclase-toxin-across-biological-membranes
#18
REVIEW
Helena Ostolaza, César Martín, David González-Bullón, Kepa B Uribe, Asier Etxaniz
Adenylate cyclase toxin (ACT) is one of the principal virulence factors secreted by the whooping cough causative bacterium Bordetella pertussis, and it has a critical role in colonization of the respiratory tract and establishment of the disease. ACT targets phagocytes via binding to the CD11b/CD18 integrin and delivers its N-terminal adenylate cyclase (AC) domain directly to the cell cytosol, where it catalyzes unregulated conversion of cytosolic ATP into cAMP upon activation by binding to cellular calmodulin...
September 21, 2017: Toxins
https://www.readbyqxmd.com/read/28933964/identification-of-novel-spg11-mutations-in-a-cohort-of-chinese-families-with-hereditary-spastic-paraplegia
#19
Juan Du, Ya-Cen Hu, Bei-Sha Tang, Hong Jiang, Lu Shen
Hereditary spastic paraplegia (HSP) is a group of clinically and genetically heterogeneous neurological diseases. To date, studies about Chinese ARHSP have been small and limited to single case. To fill this gap, we have scanned the whole exons of KIAA1840, ZFYVE26, SPG7 and CYP7B1 genes in a group of 36 unrelated ARHSP families, which is the first study conducted to investigate the mutation frequency of these ARHSP types in China. Finally, SPG11 mutations are found in 33.33% (12/36) of ARHSP patients in our study, and no mutation was identified in SPG15, SPG5 or SPG7 genes...
September 21, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/28933861/differential-effect-of-bilayer-thickness-on-sticholysin-activity
#20
Juan Palacios Ortega, Sara Garcia-Linares, Esperanza Rivera-de-Torre, Jose G Gavilanes, Alvaro Martinez-Del-Pozo, J Peter Slotte
In this study, we examined the influence of bilayer thickness on the activity of the actinoporin toxins sticholysin I and II (StnI and StnII) at 25 °C. Bilayer thickness was varied using di-monounsaturated phosphatidylcholine (PC) analogs (with 14:1, 16:1, 18:1, 20:1, and 22:1 acyl chains). In addition, N-14:0-sphingomyelin (SM) was always included because StnI and StnII are SM specific. Cholesterol was also incorporated as indicated. In cholesterol-free large unilamellar vesicles (LUV) the PC:SM molar ratio was 4:1, and when cholesterol was included, the complete molar ratio was 4:1:0...
September 21, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
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