bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCMpred—fast and precise prediction of protein residue–residue contacts from correlated mutations
Authors: Seemayer Stefan , Gruber Markus , Söding Johannes 
Published: July 2014

Abstract
Motivation : Recent breakthroughs in protein residue–residue contact prediction have made reliable de novo prediction of protein structures possible. The key was to apply statistical methods that can distinguish direct couplings between pairs of columns in a multiple sequence alignment from merely correlated pairs, i.e. to separate direct from indirect effects. Two classes of such methods exist, either relying on regularized inversion of the covariance matrix or on pseudo-likelihood maximization (PLM). Although PLM-based methods offer clearly higher precision, available tools are not sufficiently optimized and are written in interpreted languages that introduce additional overheads. This impedes the runtime and large-scale contact prediction for larger protein families, multi-domain proteins and protein–protein interactions.
Results : Here we introduce CCMpred, our performance-optimized PLM implementation in C and CUDA C. Using graphics cards in the price range of current six-core processors, CCMpred can predict contacts for typical alignments 35–113 times faster and with the same precision as the most accurate published methods. For users without a CUDA-capable graphics card, CCMpred can also run in a CPU mode that is still 4–14 times faster. Thanks to our speed-ups ( http://dictionary.cambridge.org/dictionary/british/speed-up ) contacts for typical protein families can be predicted in 15–60 s on a consumer-grade GPU and 1–6 min on a six-core CPU.
Availability and implementation : CCMpred is free and open-source software under the GNU Affero General Public License v3 (or later) available at https://bitbucket.org/soedinglab/ccmpred
Contact : johannes.soeding@mpibpc.mpg.de
Supplementary information : Supplementary data are available at Bioinformatics online.
CCBuilder: an interactive web-based tool for building, designing and assessing coiled-coil protein assemblies
Authors: Wood Christopher W. , Bruning Marc , Ibarra Amaurys Á. , Bartlett Gail J. , Thomson Andrew R. , Sessions Richard B. , Brady R Leo , Woolfson Derek N. 
Published: July 2014

Abstract
Motivation: The ability to accurately model protein structures at the atomistic level underpins efforts to understand protein folding, to engineer natural proteins predictably and to design proteins de novo . Homology-based methods are well established and produce impressive results. However, these are limited to structures presented by and resolved for natural proteins. Addressing this problem more widely and deriving truly ab initio models requires mathematical descriptions for protein folds; the means to decorate these with natural, engineered or de novo sequences; and methods to score the resulting models.
Results: We present CCBuilder, a web-based application that tackles the problem for a defined but large class of protein structure, the α-helical coiled coils. CCBuilder generates coiled-coil backbones, builds side chains onto these frameworks and provides a range of metrics to measure the quality of the models. Its straightforward graphical user interface provides broad functionality that allows users to build and assess models, in which helix geometry, coiled-coil architecture and topology and protein sequence can be varied rapidly. We demonstrate the utility of CCBuilder by assembling models for 653 coiled-coil structures from the PDB, which cover &gt;96% of the known coiled-coil types, and by generating models for rarer and de novo coiled-coil structures.
Availability and implementation: CCBuilder is freely available, without registration, at http://coiledcoils.chm.bris.ac.uk/app/cc_builder/
Contact: D.N.Woolfson@bristol.ac.uk or Chris.Wood@bristol.ac.uk
img2net: automated network-based analysis of imaged phenotypes
Authors: Breuer David , Nikoloski Zoran 
Published: July 2014

Abstract
Summary: Automated analysis of imaged phenotypes enables fast and reproducible quantification of biologically relevant features. Despite recent developments, recordings of complex networked structures, such as leaf venation patterns, cytoskeletal structures or traffic networks, remain challenging to analyze. Here we illustrate the applicability of img2net to automatedly analyze such structures by reconstructing the underlying network, computing relevant network properties and statistically comparing networks of different types or under different conditions. The software can be readily used for analyzing image data of arbitrary 2D and 3D network-like structures.
Availability and Implementation : img2net is open-source software under the GPL and can be downloaded from http://mathbiol.mpimp-golm.mpg.de/img2net/ , where supplementary information and datasets for testing are provided.
Contact : breuer@mpimp-golm.mpg.de
Kotai Antibody Builder: automated high-resolution structural modeling of antibodies
Authors: Yamashita Kazuo , Ikeda Kazuyoshi , Amada Karlou , Liang Shide , Tsuchiya Yuko , Nakamura Haruki , Shirai Hiroki , Standley Daron M. 
Published: July 2014

Abstract
Motivation: Kotai Antibody Builder is a Web service for tertiary structural modeling of antibody variable regions. It consists of three main steps: hybrid template selection by sequence alignment and canonical rules, 3D rendering of alignments and CDR-H3 loop modeling. For the last step, in addition to rule-based heuristics used to build the initial model, a refinement option is available that uses fragment assembly followed by knowledge-based scoring. Using targets from the Second Antibody Modeling Assessment, we demonstrate that Kotai Antibody Builder generates models with an overall accuracy equal to that of the best-performing semi-automated predictors using expert knowledge.
Availability and implementation: Kotai Antibody Builder is available at http://kotaiab.org
Contact: standley@ifrec.osaka-u.ac.jp
Indoleamine 2,3-dioxygenase increases p53 levels in alloreactive human T cells, and both indoleamine 2,3-dioxygenase and p53 suppress glucose uptake, glycolysis and proliferation
Authors: Eleftheriadis Theodoros , Pissas Georgios , Antoniadi Georgia , Spanoulis Aginor , Liakopoulos Vassilios , Stefanidis Ioannis 
Published: July 2014

Abstract
Indoleamine 2,3-dioxygenase (IDO) suppresses adaptive immunity by inhibiting T-cell proliferation and altering glucose metabolism. The tumor suppressor p53 also alters these cellular processes with similar results. The effect of IDO on p53 and on glucose metabolism was evaluated in alloreactive T cells. Mixed-lymphocyte reactions (MLRs) were performed in the presence or not of the IDO inhibitor, 1-dl-methyl-tryptophan (1-MT) and/or the p53 inhibitor, pifithrin-α (PFT). Cell proliferation, glucose consumption and lactate production were assessed. 1-MT increased cell proliferation, glucose influx and lactate production, whereas PFT enhanced cell proliferation and glucose influx, leaving lactate production unaffected. In MLR-derived T cells, protein analysis revealed that IDO activated general control non-derepressible 2 kinase and induced p53, p-p53 (p53 phosphorylated at serine 15) and p21. In addition, both IDO and p53 decreased glucose transporter 1 and TP53-induced glycolysis and apoptosis regulator and increased synthesis of cytochrome c oxidase 2. IDO also reduced lactate dehydrogenase-A and glutaminase 2 levels, whereas p53 left them unaffected. Neither 1-MT nor PFT affected glucose-6-phosphate dehydrogenase. In conclusion, in alloreactive T cells, IDO increases p53 levels, and both IDO and p53 inhibit cell proliferation, glucose consumption and glycolysis. Lactate production and glutaminolysis are also suppressed by IDO, but not by p53.
metaseq: a Python package for integrative genome-wide analysis reveals relationships between chromatin insulators and associated nuclear mRNA
Authors: Dale Ryan K. , Matzat Leah H. , Lei Elissa P. 
Published: July 2014

Abstract
Here we introduce metaseq, a software library written in Python, which enables loading multiple genomic data formats into standard Python data structures and allows flexible, customized manipulation and visualization of data from high-throughput sequencing studies. We demonstrate its practical use by analyzing multiple datasets related to chromatin insulators, which are DNA–protein complexes proposed to organize the genome into distinct transcriptional domains. Recent studies in Drosophila and mammals have implicated RNA in the regulation of chromatin insulator activities. Moreover, the Drosophila RNA-binding protein Shep has been shown to antagonize gypsy insulator activity in a tissue-specific manner, but the precise role of RNA in this process remains unclear. Better understanding of chromatin insulator regulation requires integration of multiple datasets, including those from chromatin-binding, RNA-binding, and gene expression experiments. We use metaseq to integrate RIP- and ChIP-seq data for Shep and the core gypsy insulator protein Su(Hw) in two different cell types, along with publicly available ChIP-chip and RNA-seq data. Based on the metaseq-enabled analysis presented here, we propose a model where Shep associates with chromatin cotranscriptionally, then is recruited to insulator complexes in trans where it plays a negative role in insulator activity.
High-throughput mutagenesis reveals functional determinants for DNA targeting by activation-induced deaminase
Authors: Gajula Kiran S. , Huwe Peter J. , Mo Charlie Y. , Crawford Daniel J. , Stivers James T. , Radhakrishnan Ravi , Kohli Rahul M. 
Published: July 2014

Abstract
Antibody maturation is a critical immune process governed by the enzyme activation-induced deaminase (AID), a member of the AID/APOBEC DNA deaminase family. AID/APOBEC deaminases preferentially target cytosine within distinct preferred sequence motifs in DNA, with specificity largely conferred by a small 9–11 residue protein loop that differs among family members. Here, we aimed to determine the key functional characteristics of this protein loop in AID and to thereby inform our understanding of the mode of DNA engagement. To this end, we developed a methodology (Sat-Sel-Seq) that couples saturation mutagenesis at each position across the targeting loop, with iterative functional selection and next-generation sequencing. This high-throughput mutational analysis revealed dominant characteristics for residues within the loop and additionally yielded enzymatic variants that enhance deaminase activity. To rationalize these functional requirements, we performed molecular dynamics simulations that suggest that AID and its hyperactive variants can engage DNA in multiple specific modes. These findings align with AID's competing requirements for specificity and flexibility to efficiently drive antibody maturation. Beyond insights into the AID-DNA interface, our Sat-Sel-Seq approach also serves to further expand the repertoire of techniques for deep positional scanning and may find general utility for high-throughput analysis of protein function.
Engineering the elongation factor Tu for efficient selenoprotein synthesis
Authors: Haruna Ken-ichi , Alkazemi Muhammad H. , Liu Yuchen , Söll Dieter , Englert Markus 
Published: July 2014

AbstractSelenocysteine (Sec) is naturally co-translationally incorporated into proteins by recoding the UGA opal codon with a specialized elongation factor (SelB in bacteria) and an RNA structural signal (SECIS element). We have recently developed a SECIS-free selenoprotein synthesis system that site-specifically—using the UAG amber codon—inserts Sec depending on the elongation factor Tu (EF-Tu). Here, we describe the engineering of EF-Tu for improved selenoprotein synthesis. A Sec-specific selection system was established by expression of human protein O6-alkylguanine-DNA alkyltransferase (hAGT), in which the active site cysteine codon has been replaced by the UAG amber codon. The formed hAGT selenoprotein repairs the DNA damage caused by the methylating agent N-methyl-N′-nitro-N-nitrosoguanidine, and thereby enables Escherichia coli to grow in the presence of this mutagen. An EF-Tu library was created in which codons specifying the amino acid binding pocket were randomized. Selection was carried out for enhanced Sec incorporation into hAGT; the resulting EF-Tu variants contained highly conserved amino acid changes within members of the library. The improved UTu-system with EF-Sel1 raises the efficiency of UAG-specific Sec incorporation to >90%, and also doubles the yield of selenoprotein production.
Homodimerization of RBPMS2 through a new RRM-interaction motif is necessary to control smooth muscle plasticity
Authors: Sagnol Sébastien , Yang Yinshan , Bessin Yannick , Allemand Fréderic , Hapkova Ilona , Notarnicola Cécile , Guichou Jean-François , Faure Sandrine , Labesse Gilles , Santa Barbara Pascal de 
Published: July 2014

AbstractIn vertebrates, smooth muscle cells (SMCs) can reversibly switch between contractile and proliferative phenotypes. This involves various molecular mechanisms to reactivate developmental signaling pathways and induce cell dedifferentiation. The protein RBPMS2 regulates early development and plasticity of digestive SMCs by inhibiting the bone morphogenetic protein pathway through its interaction with NOGGIN mRNA. RBPMS2 contains only one RNA recognition motif (RRM) while this motif is often repeated in tandem or associated with other functional domains in RRM-containing proteins. Herein, we show using an extensive combination of structure/function analyses that RBPMS2 homodimerizes through a particular sequence motif (D-x-K-x-R-E-L-Y-L-L-F: residues 39–51) located in its RRM domain. We also show that this specific motif is conserved among its homologs and paralogs in vertebrates and in its insect and worm orthologs (CPO and MEC-8, respectively) suggesting a conserved molecular mechanism of action. Inhibition of the dimerization process through targeting a conserved leucine inside of this motif abolishes the capacity of RBPMS2 to interact with the translational elongation eEF2 protein, to upregulate NOGGIN mRNA in vivo and to drive SMC dedifferentiation. Our study demonstrates that RBPMS2 possesses an RRM domain harboring both RNA-binding and protein-binding properties and that the newly identified RRM-homodimerization motif is crucial for the function of RBPMS2 at the cell and tissue levels.
Plasmodium falciparum Infection Does Not Affect Human Immunodeficiency Virus Viral Load in Coinfected Rwandan Adults
Authors: Subramaniam Krishanthi , Plank Rebeca M. , Lin Nina , Goldman-Yassen Adam , Ivan Emil , Becerril Carlos , Kemal Kimdar , Heo Moonseong , Keller Marla J. , Mutimura Eugene , Anastos Kathryn , Daily Johanna P. 
Published: July 2014

AbstractBackground.  Plasmodium falciparum infection has been reported to increase human immunodeficiency virus (HIV) viral load (VL), which can facilitate HIV transmission. We prospectively studied the impact of mild P falciparum coinfection on HIV VL in Rwanda.Methods.  We measured plasma HIV VL at presentation with malaria infection and weekly for 4 weeks after artemether-lumefantrine treatment in Rwandan adults infected with HIV with P falciparum malaria. Regression analyses were used to examine associations between malaria infection and HIV VL changes. Samples with detectable virus underwent genotypic drug-resistance testing.Results.  We enrolled 28 HIV-malaria coinfected patients and observed 27 of them for 5 weeks. Three patients (11%) were newly diagnosed with HIV. Acute P falciparum infection had no significant effect on HIV VL slope over 28 days of follow-up. Ten patients with VL &lt;40 copies/mL at enrollment maintained viral suppression throughout. Seventeen patients had a detectable VL at enrollment including 9 (53%) who reported 100% adherence to ARVs; 3 of these had detectable genotypic drug resistance.Conclusions.  Unlike studies from highly malaria-endemic areas, we did not identify an effect of P falciparum infection on HIV VL; therefore, malaria is not likely to increase HIV-transmission risk in our setting. However, routine HIV testing should be offered to adults presenting with acute malaria in Rwanda. Most importantly, we identified a large percentage of patients with detectable HIV VL despite antiretroviral (ARV) therapy. Some of these patients had HIV genotypic drug resistance. Larger studies are needed to define the prevalence and factors associated with detectable HIV VL in patients prescribed ARVs in Rwanda.
Pupillary Effects of High-dose Opioid Quantified with Infrared Pupillometry
Authors: Rollins Mark D. , Feiner John R. , Lee Jessica M. , Shah Sameer , Larson Merlin 
Published: July 2014

Abstract

Background:
The pupillary light reflex is a critical component of the neurologic examination, yet whether it is present, depressed, or absent is unknown in patients with significant opioid toxicity. Although opioids produce miosis by activating the pupillary sphincter muscle, these agents may induce significant hypercarbia and hypoxia, causing pupillary constriction to be overcome via sympathetic activation. The presence of either “pinpoint pupils” or sympathetically mediated pupillary dilation might prevent light reflex assessment. This study was designed to determine whether the light reflex remains quantifiable during opioid-induced hypercarbia and hypoxia.

Methods:
Ten volunteers were administered remifentanil with a gradually increasing infusion rate and intermittent boluses, until the increasing respiratory depression produced an oxyhemoglobin saturation of 85% or less with associated hypercarbia. Subjects’ heart rate, blood pressure, respiration, and transcutaneous carbon dioxide level were continuously recorded. Arterial blood gases and pupillary measures were taken before opioid administration, at maximal desaturation, and 15 min after recovery.

Results:
The opioid-induced oxygen desaturation (≤85%) was associated with significant hypercarbia and evidence of sympathetic activation. During maximal hypoxia and hypercarbia, the pupil displayed parasympathetic dominance (2.5 ± 0.2 mm diameter) with a robust quantifiable light reflex. The reflex amplitude was linearly related to pupil diameter.

Conclusions:
Opioid administration with significant accompanying hypercarbia and hypoxia results in pupil diameters of 2 to 3 mm and a reduced but quantifiable pupillary light reflex. The authors conclude that the pupillary examination and evaluation of the light reflex remain useful for neurologic assessment during opioid toxicity.
Transperineal Template-guided Mapping Biopsy Identifies Pathologic Differences Between Very–Low-risk and Low-risk Prostate Cancer
Authors: Merrick Gregory S. , Delatore Alexandra , Butler Wayne M. , Bennett Abbey , Fiano Ryan , Anderson Richard , Adamovich Edward 
Published: July 2014

Objectives:
Active surveillance (AS) is increasingly utilized for low-grade prostate cancer with the greatest risk being the possibility of missing a high-grade cancer. We evaluate the role of transperineal template-guided mapping biopsy (TTMB) to select patients for AS.

Methods:
A total of 131 consecutive, prospectively evaluated men with transrectal ultrasound-guided needle biopsy (TRUS)-diagnosed very low risk (Gleason score ≤6, ≤2 positive biopsies, prostate-specific antigen [PSA] density <0.15, and ≤50% involvement on any core) and low risk (Gleason score ≤6, clinical stage T1c, and PSA ≤10 ng/mL) underwent TTMB as a staging procedure. Biopsies were obtained corresponding to 24 regional biopsy locations. For each patient, the location of each positive biopsy core, the number of positive cores, and the percentage involvement of each core were reported.

Results:
After TTMB, TRUS-detected very–low-risk prostate cancer patients were less likely to be diagnosed with higher Gleason score, were less likely to have bilateral involvement, and had statistically fewer number of positive biopsy cores on TTMB. After TTMB, no cancer, very–low-risk, or low-risk prostate cancer was detected in 60 of 72 (83.3%) and 19 of 59 (32.2%) of patients with very low and low risk, respectively. In multivariate analysis, older age and low risk predicted for higher Gleason score at the time of TTMB.

Conclusions:
Very–low-risk prostate cancer patients have a significantly lower incidence of Gleason score upgrading than those with low-risk disease. After TTMB, 83.3% of patients with very–low-risk and 32.2% of patients with low-risk disease appear to be outstanding candidates for AS.
Treatment-related Hypertension as a Pharmacodynamic Biomarker for the Efficacy of Bevacizumab in Advanced Pancreas Cancer
Authors: Pant Shubham , Martin Ludmila K. , Geyer Susan , Wei Lai , Van Loon Katherine , Sommovilla Nili , Zalupski Mark , Iyer Renuka , Fogelman David , Ko Andrew H. , Bekaii-Saab Tanios 
Published: July 2014

Purpose:
Phase III studies of bevacizumab in advanced pancreas cancer (APCA) demonstrated no improvement in outcome. No validated biomarkers for bevacizumab efficacy exist. We evaluated bevacizumab-related hypertension (B-HTN) as a biomarker in APCA patients in a pooled analysis from 4 prospective clinical trials of gemcitabine-based therapy combined with bevacizumab.

Materials and Methods:
Data were collected from individual databases from 4 prospective, single-arm phase II trials. Patients were grouped according to B-HTN or no hypertension (HTN), and patients with HTN were further grouped according to highest Common Terminology Criteria for Adverse Events grade of HTN: grade 1-2 or grade 3-4. Clinical outcomes of overall survival, time to progression, overall response rate (ORR), and disease control rate (ORR+SD>16 wk) were compared.

Results:
A total of 163 patients with stage IV APCA and Eastern Cooperative Oncology Group 0-1 were included. Median age was 59 years (range, 33 to 85 y). Thirty-four patients had B-HTN, and 129 patients had no HTN. Prognostic factors were balanced between groups. Patients with any grade B-HTN had a significantly improved median overall survival (13.1 vs. 8.1 mo, P=0.0006), median time to tumor progression (7.6 vs. 5.5 mo, P=0.0074), ORR (47% vs. 16%, P=0.0001), and disease control rate (85% vs. 59%, P=0.004). There were no differences in outcomes according to HTN grade (1-2 [N=16] vs. 3-4 [N=18]).

Conclusions:
APCA patients who develop any grade of B-HTN appear to derive benefit from bevacizumab. Additional investigation is needed to identify subgroups of patients who develop B-HTN and are more likely to benefit from bevacizumab.
Comparison of Initial Experiences of Robot-Assisted Radical Cystectomy with those of Laparoscopic for Bladder Cancer
Authors: Teishima Jun , Hieda Keisuke , Inoue Shogo , Goto Keisuke , Ikeda Kenichiro , Ohara Shinya , Kobayashi Kanao , Kajiwara Mitsuru , Matsubara Akio 
Published: July 2014

Objective The aim of the present study was to evaluate perioperative outcomes in initial experiences of robot-assisted laparoscopic radical cystectomy (RARC) in comparison with those of laparoscopic radical cystectomy (LRC) for muscle-invasive or high-risk non-muscle-invasive bladder cancer. Methods We performed RARC on six patients with muscle-invasive or high-risk non-muscle-invasive bladder cancer starting in October 2011. During the same period, another five patients underwent LRC. Perioperative outcomes in initial experiences of RARC were elucidated by comparing them with those of LRC. Results Robot-assisted procedures were completed in all cases without conversion to open surgery. The median time of pneumoperitoneum was 252 minutes, and the median blood loss was 340 mL. No severe complications were observed. Perioperative outcomes did not significantly differ between RARC and LRC. Although two cases of troubles in uretero-conduit anastomosis sites were observed after LRC, no patients experienced postoperative complication related to urinary diversion after RARC. Conclusions Our data indicate that RARC is an acceptable option even in the initial period, and it may become one of the most favorable procedures for treatment of muscle-invasive bladder cancer in the near future, although more tests and longer follow-ups are required to confirm its effectiveness and safety.