bluuebunny/crossref_metadata_2025_split huggingface dataset:
mTM-align: an algorithm for fast and accurate multiple protein structure alignment
Authors: Dong Runze , Peng Zhenling , Zhang Yang , Yang Jianyi 
Published: December 2017

AbstractMotivationAs protein structure is more conserved than sequence during evolution, multiple structure alignment can be more informative than multiple sequence alignment, especially for distantly related proteins. With the rapid increase of the number of protein structures in the Protein Data Bank, it becomes urgent to develop efficient algorithms for multiple structure alignment.ResultsA new multiple structure alignment algorithm (mTM-align) was proposed, which is an extension of the highly efficient pairwise structure alignment program TM-align. The algorithm was benchmarked on four widely used datasets, HOMSTRAD, SABmark_sup, SABmark_twi and SISY-multiple, showing that mTM-align consistently outperforms other algorithms. In addition, the comparison with the manually curated alignments in the HOMSTRAD database shows that the automated alignments built by mTM-align are in general more accurate. Therefore, mTM-align may be used as a reliable complement to construct multiple structure alignments for real-world applications.Availability and implementationhttp://yanglab.nankai.edu.cn/mTM-alignSupplementary informationSupplementary data are available at Bioinformatics online.
Initial in vitro testing of a paediatric continuous-flow total artificial heart
Authors: Fukamachi Kiyotaka , Karimov Jamshid H , Horvath David J , Sunagawa Gengo , Byram Nicole A , Kuban Barry D , Moazami Nader 
Published: December 2017

Abstract

OBJECTIVES
Mechanical circulatory support has become standard therapy for adult patients with end-stage heart failure; however, in paediatric patients with congenital heart disease, the options for chronic mechanical circulatory support are limited to paracorporeal devices or off-label use of devices intended for implantation in adults. Congenital heart disease and cardiomyopathy often involve both the left and right ventricles; in such cases, heart transplantation, a biventricular assist device or a total artificial heart is needed to adequately sustain both pulmonary and systemic circulations. We aimed to evaluate the in vitro performance of the initial prototype of our paediatric continuous-flow total artificial heart.

METHODS
The paediatric continuous-flow total artificial heart pump was downsized from the adult continuous-flow total artificial heart configuration by a scale factor of 0.70 (1/3 of total volume) to enable implantation in infants. System performance of this prototype was evaluated using the continuous-flow total artificial heart mock loop set to mimic paediatric circulation. We generated maps of pump performance and atrial pressure differences over a wide range of systemic vascular resistance/pulmonary vascular resistance and pump speeds.

RESULTS
Performance data indicated left pump flow range of 0.4–4.7 l/min at 100 mmHg delta pressure. The left/right atrial pressure difference was maintained within ±5 mmHg with systemic vascular resistance/pulmonary vascular resistance ratios between 1.4 and 35, with/without pump speed modulation, verifying expected passive self-regulation of atrial pressure balance.

CONCLUSIONS
The paediatric continuous-flow total artificial heart prototype met design requirements for self-regulation and performance; in vivo pump performance studies are ongoing.
Tool for filtering PubMed search results by sample size
Authors: Baladrón Carlos , Santos-Lozano Alejandro , Aguiar Javier M , Lucia Alejandro , Martín-Hernández Juan 
Published: December 2017

Abstract

Objective
The most used search engine for scientific literature, PubMed, provides tools to filter results by several fields. When searching for reports on clinical trials, sample size can be among the most important factors to consider. However, PubMed does not currently provide any means of filtering search results by sample size. Such a filtering tool would be useful in a variety of situations, including meta-analyses or state-of-the-art analyses to support experimental therapies. In this work, a tool was developed to filter articles identified by PubMed based on their reported sample sizes.

Materials and Methods
A search engine was designed to send queries to PubMed, retrieve results, and compute estimates of reported sample sizes using a combination of syntactical and machine learning methods. The sample size search tool is publicly available for download at http://ihealth.uemc.es. Its accuracy was assessed against a manually annotated database of 750 random clinical trials returned by PubMed.

Results
Validation tests show that the sample size search tool is able to accurately (1) estimate sample size for 70% of abstracts and (2) classify 85% of abstracts into sample size quartiles.

Conclusions
The proposed tool was validated as useful for advanced PubMed searches of clinical trials when the user is interested in identifying trials of a given sample size.
Dynamics of the Immune Response in Acute Hepatitis B Infection
Authors: Stelma Femke , Willemse Sophie B , Erken Robin , de Niet Annikki , Sinnige Marjan J , van Dort Karel , Zaaijer Hans L , van Leeuwen Ester M M , Kootstra Neeltje A , Reesink Hendrik W 
Published: December 2017

AbstractBackgroundAcute hepatitis B virus infection in adults is generally self-limiting but may lead to chronicity in a minority of patients.MethodsWe included 9 patients with acute hepatitis B virus (HBV) infection and collected longitudinal follow-up samples. Natural killer (NK) cell characteristics were analyzed by flowcytometry. HBV-specific T-cell function was analyzed by in vitro stimulation with HBV peptide pools and intracellular cytokine staining.ResultsMedian baseline HBV DNA load was 5.12 log IU/mL, and median ALT was 2652 U/mL. Of 9 patients, 8 cleared HBsAg within 6 months whereas 1 patient became chronically infected. Early time points after infection showed increased CD56bright NK cells and an increased proportion of cells expressing activation markers. Most of these had normalized at week 24, while the proportion of TRAIL-positive CD56bright NK cells remained high in the chronically infected patient. In patients who cleared HBV, functional HBV-specific CD8+ and CD4+ responses could be observed, whereas in the patient who developed chronic infection, only low HBV-specific T-cell responses were observed.ConclusionsNK cells are activated early in the course of acute HBV infection. Broad and multispecific T-cell responses are observed in patients who clear acute HBV infection, but not in a patient who became chronically infected.
Surgical Treatment of Unicoronal Synostosis
Authors: Kalantar Hormozi Abdoljalil , Daryani Amir , Zali Alireza , Mohammadi Hasan Reza , Shahverediani Reza , Eskandarloo Mehdi 
Published: December 2017

Background:
Although referrals for nonsyndromic frontal plagiocephaly have been increased during the past several years, successful surgical repair of unicoronal synostosis (UCS) remains a challenge for craniofacial surgeons. Most surgical techniques followed to correct supraorbital rim elevation and temporal constrictions are being noticed less and often require a secondary revision. But this new technique consists of correcting the affected ipsilateral frontal, temporal, and superior orbital rim areas in the first operation.

Methods:
From 1995 to 2016, a total of 154 cases of UCS were operated by first author. A total of 91 patients were operated with standard technique, whereas the new technique was applied on 63. Whitaker scoring system was used for evaluation of patients after surgery.

Results:
Data analysis shows a significant difference between 2 operation techniques results (P
= 0.007). None of the patients from the new technique group required revision surgery.

Conlusions:
We believe that our new technique have less invasive osteotomy on the frontal bone and no manipulation of the orbital bone, so provide sufficient bone graft and is applicable even for younger patients (<6 months).
The prognostic effects of somatic mutations in ER-positive breast cancer
Authors: Griffith Obi L , Spies Nicholas C , Anurag Meenakshi , Griffith Malachi , Luo Jingqin , Tu Dongsheng , Yeo Belinda , Kunisaki Jason , Miller Christopher A , Krysiak Kilannin , Hundal Jasreet , Ainscough Benjamin J , Skidmore Zachary L , Campbell Katie , Kumar Runjun , Fronick Catrina , Cook Lisa , Snider Jacqueline E , Davies Sherri , Kavuri Shyam M , Chang Eric C , Magrini Vincent , Larson David E , Fulton Robert S , Liu Shuzhen , Leung Samuel , Voduc David , Bose Ron , FMedSci Mitch Dowsett , Wilson Richard K , Nielsen Torsten O , Mardis Elaine R , Ellis Matthew J 
Published: December 2017

AbstractMore than 50 genes are recurrently affected by somatic mutation in estrogen receptor positive (ER+) breast cancer but prognostic effects have not been definitively established. Primary tumor DNA was therefore subjected to targeted sequencing from 625 postmenopausal (UBC-TAM series) and 328 premenopausal (MA12 trial) hormone receptor-positive (HR+) patients. Independent validation of prognostic interactions was achieved using independent data from the METABRIC study. Associations between MAP3K1 and PIK3CA with luminal A status and TP53 mutations with Luminal B/non-luminal tumors were observed, validating the methodological approach. In UBC-TAM, NF1 frame-shift nonsense (FS/NS) mutation was validated as a poor outcome driver. For MA12, poor outcome associated with PIK3R1 mutation was similarly validated. DDR1 mutations were strongly associated with poor prognosis in UBC-TAM despite stringent false-discovery correction (q=0.0003). In conclusion, uncommon recurrent somatic mutations should be further explored to create a more complete explanation of the highly variable outcomes that typify ER+ breast cancer.
Distribution of Sigma factors delineates segregation of virulent and avirulent Mycobacterium
Authors: Gupta Aayatti Mallick , Mandal Sukhendu 
Published: December 2017

AbstractSigma factors, in combination with RNA polymerase and several transcription factors play specific role in expression of housekeeping as well as various stress responsive genes in mycobacterial species. The genus Mycobacterium includes a wide range of species under major pathogens, opportunists and non-pathogens. The number and combination of sigma factors is extremely diversified among Mycobacterium. We have performed comparative genome analysis among 40 different species of Mycobacterium whose whole genome sequence is available, in order to identify the distribution of sigma factors. The study illustrate that SigC, SigD, SigG, SigH, SigK and SigI are dominant among the true pathogens. Moreover, 16S rDNA based phylogenetic analyses distinctly differentiate the slow growing Mycobacterium from the fast growers, and clusters the true pathogens from the opportunists and non-pathogens. While evaluating the similarity coefficient upon the allotment of sigma factors of different Mycobacterium species through UPGMA dendrogram analysis, it is apparent that the true pathogens are grouped separately following the similar trend observed from evolutionary approach. Sigma factors playing dominant role in pathogenicity are found stable in nature with high aliphatic index thereby remain flexible at a wide range of temperature. The comparative distribution of six well known virulence factors of Mycobacterium - PhoP, PcaA, FbpA, Mce1B, KatG and PE_PGRS and various sigma factors justify the allotment pattern of mycobacterial sigma factors among pathogenic species. The pathogenicity responsible sigma factors elicit close resemblance with few notable characters of the known virulence factors. Thus the analysis renders that the distribution of sigma factors of different species of Mycobacterium can be a potential tool to predict the pathogenicity index of this genus.
Conservation of separase N-terminal domain
Authors: Melesse Michael , Bembenek Joshua N. , Zhulin Igor B. 
Published: December 2017

AbstractWe report a reanalysis of the sequence conservation of the cell cycle regulatory protease, separase. The sequence and structural conservation of the protease domain has long been recognized. Here we reexamine the protein sequence conservation at the N-terminus using PSI-BLAST analysis and report our discovery of a cysteine rich motif (CxCXXC) conserved in nematodes and vertebrates. This motif is found in a solvent exposed linker region connecting two TPR-like helical motifs. Mutation of this motif in Caenorhabditis elegans separase leads to a temperature sensitive hypomorphic protein, and several N-terminal residues identified as intragenic suppressors are not conserved. Conservation of this motif in multiple organisms raises the possibility that the motif plays similar roles across species.
Functional Compensation Between Hematopoietic Stem CellsIn Vivo
Authors: Nguyen Lisa , Wang Zheng , Chu Elizabeth , Eerdeng Jiya , Chowdhury Adnan Y. , Lu Rong 
Published: December 2017

AbstractIn most organ systems, regeneration is a coordinated effort that involves many stem cells, but little is known about whether and how individual stem cells compensate for the functional deficiencies of other stem cells. Functional compensation between stem cells is critically important during disease progression and treatment. Here, we show how individual hematopoietic stem cells (HSCs) in a mouse heterogeneously compensate for the deficiencies of other HSCs’ during lymphopoiesis by increasing their clonal expansion at specific differentiation stages. This compensation rescues the overall blood supply and influences blood cell types outside of the deficient lineages in distinct patterns. We have identified the molecular regulators and signaling pathways in HSCs that are involved in this process. Our data demonstrate how stem cells interact with each other to constitute a coordinated network that is robust enough to withstand minor functional disruptions. Exploiting the innate compensation capacity of stem cell networks may improve the prognosis and treatment of many diseases.
Micropattern differentiation of mouse pluripotent stem cells recapitulates embryo regionalized cell fate patterning
Authors: Morgani Sophie M. , Metzger Jakob J. , Nichols Jennifer , Siggia Eric D. , Hadjantonakis Anna-Katerina 
Published: December 2017

AbstractDuring gastrulation epiblast cells exit pluripotency as they specify and spatially arrange the three germ layers of the embryo. Similarly, human pluripotent stem cells (PSCs) undergo spatially organized fate specification on micropatterned surfaces. Since in vivo validation is not possible for the human, we developed a mouse PSC micropattern system and, with direct comparisons to mouse embryos, reveal the robust specification of distinct regional identities. BMP, WNT, ACTIVIN and FGF directed mouse epiblast-like cells to undergo an epithelial-to-mesenchymal transition and radially pattern posterior mesoderm fates. Conversely, WNT, ACTIVIN and FGF patterned anterior identities, including definitive endoderm. By contrast, epiblast stem cells, a developmentally advanced state, only specified anterior identities, but without patterning. The mouse micropattern system offers a robust scalable method to generate regionalized cell types present in vivo, resolve how signals promote distinct identities and generate patterns, and compare mechanisms operating in vivo and in vitro and across species.
Regulation of mitochondrial dynamics by Aurora A kinase
Authors: Grant Rhys , Abdelbaki Ahmed , Bertoldi Alessia , Gavilan Maria P , Mansfeld Jörg , Glover David M , Lindon Catherine 
Published: December 2017

AbstractAurora A kinase (AURKA) is a major regulator of mitosis and an important driver of cancer progression. The roles of AURKA outside of mitosis, and how these might contribute to cancer progression, are not well understood. Here we show that a fraction of cytoplasmic AURKA is associated with mitochondria, co-fractionating in cell extracts and interacting with mitochondrial proteins by reciprocal co-immunoprecipitation. We have also found that the dynamics of the mitochondrial network are sensitive to AURKA inhibition, depletion or overexpression. This can account for the different mitochondrial morphologies observed in RPE1 and U2OS cell lines, which show very different levels of expression of AURKA. We identify the mitochondrial fraction of AURKA as influencing mitochondrial morphology, since an N-terminally truncated version of the kinase that does not localize to mitochondria does not affect the mitochondrial network. We identify a cryptic mitochondrial targeting sequence in the AURKA N-terminus and discuss how alternative conformations of the protein may influence its cytoplasmic fate.
Cytosolic delivery of large supramolecular protein complexes arranged on DNA nanopegboards
Authors: Nikolov Pavel M. , Koßmann Katja J. , Schilling Alessa , Angelin Alessandro , Brglez Josipa , Klein Alina , Tampé Robert , Rabe Kersten S. , Niemeyer Christof M. 
Published: December 2017

AbstractA generic methodology for cytosolic delivery of large supramolecular multiprotein complexes into living cells is described that takes advantage of the highly-controllable bottom-up fabrication of protein-decorated DNA nanostructures and the microfluidic “cell squeezing” technique. Therein, cells are deformed upon passage through a narrow constriction leading to formation of transient holes in the cell membrane that enable the diffusion of the protein-DNA nanostructures from the surrounding buffer into the cytosol. A diverse set of multiprotein complexes was assembled on DNA origami nanostructures using streptavidin and the sensitive glucose sensor protein FLIP as model systems. We demonstrate that our approach allows for the direct cytosolic delivery of these multifunctional protein complexes into the cytosol of HeLa cells. We also demonstrate that targeting groups can be incorporated into the protein-DNA nanoassemblies to enable their intracellular targeting to cytosolic compartments, such as the cytoskeleton or nucleus. We believe that this methodology will open up novel strategies for research in fundamental cell biology, such as the reverseengineering of the supramolecular machinery involved in gene regulation, cell signalling, or cell division. Furthermore, direct applications in immunotherapy can be foreseen.
Candidate cancer driver mutations in superenhancers and long-range chromatin interaction networks
Authors: Wadi Lina , Uusküla-Reimand Liis , Isaev Keren , Shuai Shimin , Huang Vincent , Liang Minggao , Thompson J. Drew , Li Yao , Ruan Luyao , Paczkowska Marta , Krassowski Michal , Dzneladze Irakli , Kron Ken , Murison Alexander , Mazrooei Parisa , Bristow Robert G. , Simpson Jared T. , Lupien Mathieu , Wilson Michael D. , Stein Lincoln D. , Boutros Paul C. , Reimand Jüri 
Published: December 2017

AbstractA comprehensive catalogue of the mutations that drive tumorigenesis and progression is essential to understanding tumor biology and developing therapies. Protein-coding driver mutations have been well-characterized by large exome-sequencing studies, however many tumors have no mutations in protein-coding driver genes. Non-coding mutations are thought to explain many of these cases, however few non-coding drivers besides TERT promoter are known. To fill this gap, we analyzed 150,000 cis-regulatory regions in 1,844 whole cancer genomes from the ICGC-TCGA PCAWG project. Using our new method, ActiveDriverWGS, we found 41 frequently mutated regulatory elements (FMREs) enriched in non-coding SNVs and indels (FDR<0.05) characterized by aging-associated mutation signatures and frequent structural variants. Most FMREs are distal from genes, reported here for the first time and also recovered by additional driver discovery methods. FMREs were enriched in super-enhancers, H3K27ac enhancer marks of primary tumors and long-range chromatin interactions, suggesting that the mutations drive cancer by distally controlling gene expression through threedimensional genome organization. In support of this hypothesis, the chromatin interaction network of FMREs and target genes revealed associations of mutations and differential gene expression of known and novel cancer genes (e.g., CNNB1IP1, RCC1), activation of immune response pathways and altered enhancer marks. Thus distal genomic regions may include additional, infrequently mutated drivers that act on target genes via chromatin loops. Our study is an important step towards finding such regulatory regions and deciphering the somatic mutation landscape of the non-coding genome.
The cancer-mutation network and the number and specificity of driver mutations
Authors: Iranzo Jaime , Martincorena Iñigo , Koonin Eugene V. 
Published: December 2017

AbstractCancer genomics has produced extensive information on cancer-associated genes but the number and specificity of cancer driver mutations remains a matter of debate. We constructed a bipartite network in which 7665 tumors from 30 cancer types are connected via shared mutations in 198 previously identified cancer-associated genes. We show that 27% of the tumors can be assigned to statistically supported modules, most of which encompass 1-2 cancer types. The rest of the tumors belong to a diffuse network component suggesting lower gene-specificity of driver mutations. Linear regression of the mutational loads in cancer-associated genes was used to estimate the number of drivers required for the onset of different cancers. The mean number of drivers is ~2, with a range of 1 to 5. Cancers that are associated to modules had more drivers than those from the diffuse network component, suggesting that unidentified and/or interchangeable drivers exist in the latter.