bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of MHC II ubiquitination inhibits the activation and differentiation of CD4 T cells
Authors: Ishikawa Rikiya , Kajikawa Mizuho , Ishido Satoshi 
Published: December 2013

Abstract
Peptide–MHC class II complexes (pMHC II) are degraded by MARCH-I-mediated ubiquitination, and the stabilization of pMHC II by loss of its ubiquitination is one phenotype defining the activation of conventional dendritic cells (cDCs). However, the role of such stabilization of pMHC II in the context of T-cell activation/differentiation remains unclear. Here, we show that loss of pMHC II ubiquitination inhibits the activation and differentiation of CD4 T cells, probably through down-regulation of CD18/integrin β2 and their diminished IL-12 production in a cell intrinsic manner. The cDCs generated from mice whose pMHC II ubiquitination is inhibited had a decreased ability to activate naive CD4 T cells and induce Th1/Th17 differentiation. In addition, cDCs whose MHC II ubiquitination was inhibited showed down-regulation of CD18/integrin beta 2 and of IL-12 production. This unexpected finding suggests that loss of MHC II ubiquitination contributes to the negative feedback of CD4 T-cell immune responses.
RNase L restricts the mobility of engineered retrotransposons in cultured human cells
Authors: Zhang Ao , Dong Beihua , Doucet Aurélien J. , Moldovan John B. , Moran John V. , Silverman Robert H. 
Published: December 2013

Abstract
Retrotransposons are mobile genetic elements, and their mobility can lead to genomic instability. Retrotransposon insertions are associated with a diverse range of sporadic diseases, including cancer. Thus, it is not a surprise that multiple host defense mechanisms suppress retrotransposition. The 2′,5′-oligoadenylate (2-5A) synthetase (OAS)-RNase L system is a mechanism for restricting viral infections during the interferon antiviral response. Here, we investigated a potential role for the OAS-RNase L system in the restriction of retrotransposons. Expression of wild type (WT) and a constitutively active form of RNase L (NΔ385), but not a catalytically inactive RNase L mutant (R667A), impaired the mobility of engineered human LINE-1 (L1) and mouse intracisternal A-type particle retrotransposons in cultured human cells. Furthermore, WT RNase L, but not an inactive RNase L mutant (R667A), reduced L1 RNA levels and subsequent expression of the L1-encoded proteins (ORF1p and ORF2p). Consistently, confocal immunofluorescent microscopy demonstrated that WT RNase L, but not RNase L R667A, prevented formation of L1 cytoplasmic foci. Finally, siRNA-mediated depletion of endogenous RNase L in a human ovarian cancer cell line (Hey1b) increased the levels of L1 retrotransposition by ∼2-fold. Together, these data suggest that RNase L might function as a suppressor of structurally distinct retrotransposons.
Single molecule analysis ofThermus thermophilusSSB protein dynamics on single-stranded DNA
Authors: Zhang Jichuan , Zhou Ruobo , Inoue Jin , Mikawa Tsutomu , Ha Taekjip 
Published: December 2013

AbstractSingle-stranded (ss) DNA binding (SSB) proteins play central roles in DNA replication, recombination and repair in all organisms. We previously showed that Escherichia coli (Eco) SSB, a homotetrameric bacterial SSB, undergoes not only rapid ssDNA-binding mode transitions but also one-dimensional diffusion (or migration) while remaining bound to ssDNA. Whereas the majority of bacterial SSB family members function as homotetramers, dimeric SSB proteins were recently discovered in a distinct bacterial lineage of extremophiles, the Thermus–Deinococcus group. Here we show, using single-molecule fluorescence resonance energy transfer (FRET), that homodimeric bacterial SSB from Thermus thermophilus (Tth) is able to diffuse spontaneously along ssDNA over a wide range of salt concentrations (20–500 mM NaCl), and that TthSSB diffusion can help transiently melt the DNA hairpin structures. Furthermore, we show that two TthSSB molecules undergo transitions among different DNA-binding modes while remaining bound to ssDNA. Our results extend our previous observations on homotetrameric SSBs to homodimeric SSBs, indicating that the dynamic features may be shared among different types of SSB proteins. These dynamic features of SSBs may facilitate SSB redistribution and removal on/from ssDNA, and help recruit other SSB-interacting proteins onto ssDNA for subsequent DNA processing in DNA replication, recombination and repair.
Structure modulation of helix 69 from Escherichia coli 23S ribosomal RNA by pseudouridylations
Authors: Jiang Jun , Aduri Raviprasad , Chow Christine S. , SantaLucia John 
Published: December 2013

Abstract
Helix 69 (H69) is a 19-nt stem-loop region from the large subunit ribosomal RNA. Three pseudouridine (Ψ) modifications clustered in H69 are conserved across phylogeny and known to affect ribosome function. To explore the effects of Ψ on the conformations of Escherichia coli H69 in solution, nuclear magnetic resonance spectroscopy was used to reveal the structural differences between H69 with (ΨΨΨ) and without (UUU) Ψ modifications. Comparison of the two structures shows that H69 ΨΨΨ has the following unique features: (i) the loop region is closed by a Watson–Crick base pair between Ψ1911 and A1919, which is potentially reinforced by interactions involving Ψ1911N1H and (ii) Ψ modifications at loop residues 1915 and 1917 promote base stacking from Ψ1915 to A1918. In contrast, the H69 UUU loop region, which lacks Ψ modifications, is less organized. Structure modulation by Ψ leads to alteration in conformational behavior of the 5' half of the H69 loop region, observed as broadening of C1914 non-exchangeable base proton resonances in the H69 ΨΨΨ nuclear magnetic resonance spectra, and plays an important biological role in establishing the ribosomal intersubunit bridge B2a and mediating translational fidelity.
Active site plasticity enables metal-dependent tuning of Cas5d nuclease activity in CRISPR-Cas type I-C system
Authors: Punetha Ankita , Sivathanu Raveendran , Anand Baskaran 
Published: December 2013

Abstract
Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) in association with CRISPR-associated (Cas) proteins constitutes a formidable defense system against mobile genetic elements in prokaryotes. In type I-C, the ribonucleoprotein surveillance complex comprises only three Cas proteins, namely, Cas5d, Csd1 and Csd2. Unlike type I-E that uses Cse3/CasE for metal-independent CRISPR RNA maturation, type I-C that lacks this deputes Cas5d to process the pre-crRNA. Here, we report the promiscuous DNase activity of Cas5d in presence of divalent metals. Remarkably, the active site that renders RNA hydrolysis may be tuned by metal to act on DNA substrates too. Further, the realization that Csd1 is a fusion of its functional homolog Cse1/CasA and Cse2/CasB forecasts that the stoichiometry of the constituents of the surveillance complex in type I-C may differ from type I-E. Although Csd2 seems to be inert, Csd1 too exhibits RNase and metal-dependent DNase activity. Thus, in addition to their proposed functions, the DNase activity of Cas5d and Csd1 may also enable them to be co-opted in adaptation and interference stages of CRISPR immunity wherein interaction with DNA substrates is involved.
Molecular mechanisms of adaptation emerging from the physics and evolution of nucleic acids and proteins
Authors: Goncearenco Alexander , Ma Bin-Guang , Berezovsky Igor N. 
Published: December 2013

AbstractDNA, RNA and proteins are major biological macromolecules that coevolve and adapt to environments as components of one highly interconnected system. We explore here sequence/structure determinants of mechanisms of adaptation of these molecules, links between them, and results of their mutual evolution. We complemented statistical analysis of genomic and proteomic sequences with folding simulations of RNA molecules, unraveling causal relations between compositional and sequence biases reflecting molecular adaptation on DNA, RNA and protein levels. We found many compositional peculiarities related to environmental adaptation and the life style. Specifically, thermal adaptation of protein-coding sequences in Archaea is characterized by a stronger codon bias than in Bacteria. Guanine and cytosine load in the third codon position is important for supporting the aerobic life style, and it is highly pronounced in Bacteria. The third codon position also provides a tradeoff between arginine and lysine, which are favorable for thermal adaptation and aerobicity, respectively. Dinucleotide composition provides stability of nucleic acids via strong base-stacking in ApG dinucleotides. In relation to coevolution of nucleic acids and proteins, thermostability-related demands on the amino acid composition affect the nucleotide content in the second codon position in Archaea.
The structure of metallo-DNA with consecutive thymine–HgII–thymine base pairs explains positive entropy for the metallo base pair formation
Authors: Yamaguchi Hiroshi , Šebera Jakub , Kondo Jiro , Oda Shuji , Komuro Tomoyuki , Kawamura Takuya , Dairaku Takenori , Kondo Yoshinori , Okamoto Itaru , Ono Akira , Burda Jaroslav V. , Kojima Chojiro , Sychrovský Vladimír , Tanaka Yoshiyuki 
Published: December 2013

Abstract
We have determined the three-dimensional (3D) structure of DNA duplex that includes tandem HgII-mediated T–T base pairs (thymine–HgII–thymine, T–HgII–T) with NMR spectroscopy in solution. This is the first 3D structure of metallo-DNA (covalently metallated DNA) composed exclusively of ‘NATURAL’ bases. The T–HgII–T base pairs whose chemical structure was determined with the 15N NMR spectroscopy were well accommodated in a B-form double helix, mimicking normal Watson–Crick base pairs. The Hg atoms aligned along DNA helical axis were shielded from the bulk water. The complete dehydration of Hg atoms inside DNA explained the positive reaction entropy (ΔS) for the T–HgII–T base pair formation. The positive ΔS value arises owing to the HgII dehydration, which was approved with the 3D structure. The 3D structure explained extraordinary affinity of thymine towards HgII and revealed arrangement of T–HgII–T base pairs in metallo-DNA.
Solution structure and tandem DNA recognition of the C-terminal effector domain of PmrA from Klebsiella pneumoniae
Authors: Lou Yuan-Chao , Wang Iren , Rajasekaran M. , Kao Yi-Fen , Ho Meng-Ru , Hsu Shang-Te Danny , Chou Shan-Ho , Wu Shih-Hsiung , Chen Chinpan 
Published: December 2013

Abstract
Klebsiella pneumoniae PmrA is a polymyxin-resistance-associated response regulator. The C-terminal effector/DNA-binding domain of PmrA (PmrAC) recognizes tandem imperfect repeat sequences on the promoters of genes to induce antimicrobial peptide resistance after phosphorylation and dimerization of its N-terminal receiver domain (PmrAN). However, structural information concerning how phosphorylation of the response regulator enhances DNA recognition remains elusive. To gain insights, we determined the nuclear magnetic resonance solution structure of PmrAC and characterized the interactions between PmrAC or BeF3−-activated full-length PmrA (PmrAF) and two DNA sequences from the pbgP promoter of K. pneumoniae. We showed that PmrAC binds to the PmrA box, which was verified to contain two half-sites, 5′-CTTAAT-3′ and 5′-CCTAAG-3′, in a head-to-tail fashion with much stronger affinity to the first than the second site without cooperativity. The structural basis for the PmrAC–DNA complex was investigated using HADDOCK docking and confirmed by paramagnetic relaxation enhancement. Unlike PmrAC, PmrAF recognizes the two sites simultaneously and specifically. In the PmrAF–DNA complex, PmrAN may maintain an activated homodimeric conformation analogous to that in the free form and the interactions between two PmrAC molecules aid in bending and binding of the DNA duplex for transcription activation.
Carbon source-dependent alteration of Puf3p activity mediates rapid changes in the stabilities of mRNAs involved in mitochondrial function
Authors: Miller Melanie A. , Russo Joseph , Fischer Anthony D. , Lopez Leban Florencia A. , Olivas Wendy M. 
Published: December 2013

Abstract
The Puf family of RNA-binding proteins regulates gene expression primarily by interacting with the 3′ untranslated region (3′ UTR) of targeted mRNAs and inhibiting translation and/or stimulating decay. Physical association and computational analyses of yeast Puf3p identified &gt;150 potential mRNA targets involved in mitochondrial function. However, only COX17 has been established as a target of Puf3p-mediated deadenylation and decapping. We have identified 10 new targets that are rapidly degraded in a Puf3p-dependent manner. We also observed changes in Puf3p activity in response to environmental conditions. Puf3p promotes rapid degradation of mRNA targets in the fermentable carbon source dextrose. However, Puf3p-mediated decay activity is inhibited in carbon sources that require mitochondrial function for efficient cell growth. In addition, the activity of Puf3p is rapidly altered by changing the carbon source. PUF3 expression is not decreased at the RNA or protein level by different carbon sources and localization is not significantly altered, suggesting that Puf3p activity is regulated posttranslationally. Finally, under conditions when Puf3p is unable to stimulate decay, Puf3p can still bind its target mRNAs. Together, these experiments provide insight into the carbon source-specific control of Puf3p activity and how such alterations allow Puf3p to dynamically regulate mitochondrial function.
Tracking the processing of damaged DNA double-strand break ends by ligation-mediated PCR: increased persistence of 3′-phosphoglycolate termini in SCAN1 cells
Authors: Akopiants Konstantin , Mohapatra Susovan , Menon Vijay , Zhou Tong , Valerie Kristoffer , Povirk Lawrence F. 
Published: December 2013

AbstractTo track the processing of damaged DNA double-strand break (DSB) ends in vivo, a method was devised for quantitative measurement of 3′-phosphoglycolate (PG) termini on DSBs induced by the non-protein chromophore of neocarzinostatin (NCS-C) in the human Alu repeat. Following exposure of cells to NCS-C, DNA was isolated, and labile lesions were chemically stabilized. All 3′-phosphate and 3′-hydroxyl ends were enzymatically capped with dideoxy termini, whereas 3′-PG ends were rendered ligatable, linked to an anchor, and quantified by real-time Taqman polymerase chain reaction. Using this assay and variations thereof, 3′-PG and 3′-phosphate termini on 1-base 3′ overhangs of NCS-C-induced DSBs were readily detected in DNA from the treated lymphoblastoid cells, and both were largely eliminated from cellular DNA within 1 h. However, the 3′-PG termini were processed more slowly than 3′-phosphate termini, and were more persistent in tyrosyl-DNA phosphodiesterase 1-mutant SCAN1 than in normal cells, suggesting a significant role for tyrosyl-DNA phosphodiesterase 1 in removing 3′-PG blocking groups for DSB repair. DSBs with 3′-hydroxyl termini, which are not directly induced by NCS-C, were formed rapidly in cells, and largely eliminated by further processing within 1 h, both in Alu repeats and in heterochromatic α-satellite DNA. Moreover, absence of DNA-PK in M059J cells appeared to accelerate resolution of 3′-PG ends.
Converging pathways involving microRNA-206 and the RNA-binding protein KSRP control post-transcriptionally utrophin A expression in skeletal muscle
Authors: Amirouche Adel , Tadesse Helina , Miura Pedro , Bélanger Guy , Lunde John A. , Côté Jocelyn , Jasmin Bernard J. 
Published: December 2013

Abstract
Several reports have previously highlighted the potential role of miR-206 in the post-transcriptional downregulation of utrophin A in cultured cells. Along those lines, we recently identified K-homology splicing regulator protein (KSRP) as an important negative regulator in the post-transcriptional control of utrophin A in skeletal muscle. We sought to determine whether these two pathways act together to downregulate utrophin A expression in skeletal muscle. Surprisingly, we discovered that miR-206 overexpression in cultured cells and dystrophic muscle fibers causes upregulation of endogenous utrophin A levels. We further show that this upregulation of utrophin A results from the binding of miR-206 to conserved sites located in the 3′-UTR (untranslated region) of KSRP, thus causing the subsequent inhibition of KSRP expression. This miR-206-mediated decrease in KSRP levels leads, in turn, to an increase in the expression of utrophin A due to a reduction in the activity of this destabilizing RNA-binding protein. Our work shows that miR-206 can oscillate between direct repression of utrophin A expression via its 3′-UTR and activation of its expression through decreased availability of KSRP and interactions with AU-rich elements located within the 3′-UTR of utrophin A. Our study thus reveals that two apparent negative post-transcriptional pathways can act distinctively as molecular switches causing repression or activation of utrophin A expression.
Immortality, but not oncogenic transformation, of primary human cells leads to epigenetic reprogramming of DNA methylation and gene expression
Authors: Gordon Katrina , Clouaire Thomas , Bao Xun X. , Kemp Sadie E. , Xenophontos Maria , de Las Heras Jose Ignacio , Stancheva Irina 
Published: December 2013

Abstract
Tumourigenic transformation of normal cells into cancer typically involves several steps resulting in acquisition of unlimited growth potential, evasion of apoptosis and non-responsiveness to growth inhibitory signals. Both genetic and epigenetic changes can contribute to cancer development and progression. Given the vast genetic heterogeneity of human cancers and difficulty to monitor cancer-initiating events in vivo, the precise relationship between acquisition of genetic mutations and the temporal progression of epigenetic alterations in transformed cells is largely unclear. Here, we use an in vitro model system to investigate the contribution of cellular immortality and oncogenic transformation of primary human cells to epigenetic reprogramming of DNA methylation and gene expression. Our data demonstrate that extension of replicative life span of the cells is sufficient to induce accumulation of DNA methylation at gene promoters and large-scale changes in gene expression in a time-dependent manner. In contrast, continuous expression of cooperating oncogenes in immortalized cells, although essential for anchorage-independent growth and evasion of apoptosis, does not affect de novo DNA methylation at promoters and induces subtle expression changes. Taken together, these observations imply that cellular immortality promotes epigenetic adaptation to highly proliferative state, whereas transforming oncogenes confer additional properties to transformed human cells.
Validation of a Medicare Claims-based Algorithm for Identifying Freestanding Ambulatory Surgery Centers
Authors: Hollingsworth John M. , Dunn Rodney L. , Suskind Anne M. , Banerjee Mousumi , Hollenbeck Brent K. 
Published: December 2013

Background and Objective:
With visits to ambulatory surgery centers (ASCs) on the rise, accountability in the care provided by these facilities and the surgeons who staff them is required. This requires the ability to measure and monitor ASC-based care over time. For this reason, we developed and validated a claims-based algorithm to identify ASCs.

Research Design:
Using a 20% sample of Medicare claims (2002–2008), we developed 3 ASC definitions. Definition 1 identified unique facilities with tax identification numbers and appropriate Place of Service and Type of Service codes. Definition 2 had the same conditions but also required specific Specialty codes. Definition 3 involved a multistep cleansing stage, in which facilities with indeterminate information in the fields of interest were eliminated. We assessed agreement between these definitions and findings from alternative data sources.

Results:
Placing additional requirements on how a freestanding ASC was defined within Medicare claims helped in the refinement of our algorithm. Agreement on the number of unique ASCs in Florida over the study interval was greatest between Definition 3 and the State Ambulatory Surgery Databases (concordance correlation coefficient=0.984; 95%, confidence interval, 0.967–0.992). With the Provider of Services Extract serving as the reference standard, our algorithm (based on Definition 3) had a positive predictive value of 99.0% (95% confidence interval, 98.6%–99.4%) for determining health care markets that experienced the opening of an ASC.

Conclusions:
The consequent inference is that our algorithm represents an accurate tool for distinguishing and tracking ASCs in Medicare data.
Assessing the Use of Antiviral Treatment to Control Influenza
Authors: Kramer Sarah , Bansal Shweta 
Published: December 2013

AbstractVaccines are the cornerstone of influenza control policy, but can suffer from several drawbacks. Seasonal influenza vaccines are prone to production problems and low efficacies, while pandemic vaccines are unlikely to be available in time to slow a rapidly spreading global outbreak. Antiviral therapy was found to be beneficial during the influenza A(H1N1)pdm09 pandemic even with limited use; however, antiviral use has decreased further since then. We seek to determine the role antiviral therapy can play in pandemic and seasonal influenza control on the population level, and to find optimized strategies for more efficient use of treatment. Using an age-structured contact network model for an urban population, we find that while a conservative antiviral therapy strategy cannot replace a robust influenza vaccine, it can play a role in reducing attack rates and eliminating outbreaks.
Modelling of magnetic data for scaling geology
Authors: Bansal A.R. , Dimri V.P. 
Published: December 2013

ABSTRACTInterpretation of magnetic data can be carried out either in the space or frequency domain. The interpretation in the frequency domain is computationally convenient because convolution becomes multiplication. The frequency domain approach assumes that the magnetic sources distribution has a random and uncorrelated distribution. This approach is modified to include random and fractal distribution of sources on the basis of borehole data. The physical properties of the rocks exhibit scaling behaviour which can be defined as P(k) = Ak−β, where P(k) is the power spectrum as a function of wave number (k), and A and β are the constant and scaling exponent, respectively. A white noise distribution corresponds to β = 0. The high resolution methods of power spectral estimation e.g. maximum entropy method and multi‐taper method produce smooth spectra. Therefore, estimation of scaling exponents is more reliable. The values of β are found to be related to the lithology and heterogeneities in the crust. The modelling of magnetic data for scaling distribution of sources leads to an improved method of interpreting the magnetic data known as the scaling spectral method. The method has found applicability in estimating the basement depth, Curie depth and filtering of magnetic data.