bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein Multiple Alignments: Sequence-based vs Structure-based Programs
Authors: Carpentier Mathilde , Chomilier Jacques 
Published: September 2018

ABSTRACTFacing the huge increase of information about proteins, classification has reached the level of a compulsory task, essential for assigning a function to a given sequence, by means of comparison to existing data. Multiple sequence alignment programs have been proven to be very useful and they have already been evaluated. In this paper we wished to evaluate the added value provided by taking into account structures. We compared the multiple alignments resulting from 24 programs, either based on sequence, structure, or both, to reference alignments deposited in five databases. Reference databases, on their side, can be split in two: more automatic ones, and more manually ones. Scores have been attributed to each program. As a global rule of thumb, five groups of methods emerge, with the lead to two of the structure-based programs. This advantage is increased at low levels of sequence identity among aligned proteins, or for residues in regular secondary structures or buried. Concerning gap management, sequence-based programs place less gaps than structure-based programs. Concerning the databases, the alignments from the manually built databases are the more challenging for the programs.
The role of BMP6 in the proliferation and differentiation of chicken cartilage cells
Authors: Ye Fei , Xu Hengyong , Yin Huadong , Zhao Xiaoling , Li Diyan , Zhu Qing , Wang Yan 
Published: September 2018

AbstractPrevious studies have indicated that bone morphogenetic protein (BMP) 6 plays an important role in skeletal system development and progression. However, the mechanism underlying the effects of BMP6 in cartilage cell proliferation and differentiation remains unknown. In this study, cartilage cells were isolated from shanks of chicken embryos and treated with different concentrations of GH. Cell proliferation and differentiation potential was assessed using real-time polymerase chain reaction (RT-PCR) and CCK-8 assays in vitro. The results showed that at 48 h, the Collagen II and BMP6 expression levels in 50 ng/μl GH-treated cartilage cells were significantly higher than in groups treated with 100 ng/μl or 200 ng/μl GH. We further observed that knockdown of BMP6 in cartilage cells led to significantly decreased expression levels of Collagen II and Collagen X. Moreover, the suppression of BMP6 expression by a specific siRNA vector led to significantly decreased expression levels of IGF1R, JAK, PKC, PTH, IHH and PTHrP. Taken together, our data suggest that BMP6 may play a critical role in chicken cartilage cell proliferation and differentiation through the regulation of IGF1, JAK2, PKC, PTH, and Ihh-PTHrP signaling pathways.
Glutathione S-Transferase Genotype polymorphism and Primary Open-Angle Glaucoma in an Italian population
Authors: Saccà Sergio C , Cutolo Carlo A , Gandolfi Stefano , Marchini Giorgio , Quaranta Luciano , Izzotti Alberto , Rossi Tommaso , Traverso Carlo Enrico 
Published: September 2018

AbstractPurposeOxidative damage to the trabecular meshwork (TM) represents one of the pathogenic mechanisms leading to primary open angle glaucoma (POAG). Glutathione S-transferase mu 1 (GSTM1) may neutralizes reactive oxygen species protecting the TM. The present paper investigates the prevalence of GSTM1 null genotype in an Italian population, and its association with POAG treated either medically or surgically.MethodsIn a case-control study, the GSTM1 genotype was identified in POAGs and controls. The POAGs patients were divided in two groups: medical POAGs and surgical POAGS. Medical POAGs consisted of patients with a well-controlled intraocular pressure (IOP) by IOP-lowering medications and a stable visual field (VF). Patients with an uncontrolled IOP and a progressing VF that were submitted to incisional surgery formed the surgical POAGs’ group.ResultsWe enrolled 104 medical POAGs, 158 surgical POAGs and 263 Controls. No significative differences between the groups existed regarding age and gender (p=0.275 and p=0.950, respectively). All the enrolled subjects were Caucasian of Italian descents. The GSTM1 null genotype was identified in 57 (45.2%) medical POAGs, 91 (57.6%) surgical POAGs and, 119 (45.3%) controls (p=0.033). The association between medical POAG and GSTM1 null status was non-significant (OR= 1.44, 95% IC = 0.86 to 2.39) whereas the association was significant for surgical POAGs (OR= 2.01, 95% IC= 1.26 to 3.21)ConclusionsOur results showed an association between the GSTM1 null genotype and glaucoma that require surgery in an Italian population. GSTM1 null genotype detection may help to identify high-risk glaucoma patients that require a closer follow-up and a more aggressive treatments.
Sea lettuce systematics: lumping or splitting?
Authors: Batista Manuela Bernardes , Cunha Regina L. , Castilho Rita , Horta Paulo Antunes 
Published: September 2018

AbstractPhylogenetic relationships within sea lettuce species belonging to the genusUlvais a daunting challenge given the scarcity of diagnostic morphological features and the pervasive phenotypic plasticity. With more than 100 species described on a morphological basis, an accurate evaluation of its diversity is still missing. Here we analysed 277 chloroplast-encoded gene sequences (43 from this study), representing 35 nominal species ofUlvafrom the Pacific, Indian Ocean, and Atlantic (with a particular emphasis on the Brazilian coast) in an attempt to solve the complex phylogenetic relationships within this widespread genus. Maximum likelihood, Bayesian analyses and species delimitation tests support the existence of 22 evolutionary significant units (ESUs), lumping the currently recognized number of species. All individuals sampled throughout an extensive area of the Brazilian coast were included within two distinct ESUs. Most of the clades retrieved in the phylogenetic analyses do not correspond to a single nominal species. Geographic range evolution indicated that the ancestor ofUlvahad a distribution restricted to the temperate North Pacific. The dating analysis estimated its origin during the Upper Cretaceous at 75.8 million years (myr) ago but most of the cladogenetic events within the genus occurred in the last ten myr. Pervasive human-mediated gene flow through ballast water and widespread morphologic plasticity are the most likely explanations for the difficulty in establishing a reliable phylogenetic framework for this conspicuous, widespred and many times abundant green algae morphotype.
HLA RNAseq reveals high allele-specific variability in mRNA expression
Authors: Johansson Tiira , Yohannes Dawit A. , Koskela Satu , Partanen Jukka , Saavalainen Päivi 
Published: September 2018

AbstractThe HLA gene complex is the most important, single genetic factor in susceptibility to most diseases with autoimmune or autoinflammatory origin and in transplantation matching. The majority of the studies have focused on the huge allelic variation in these genes; only a few studies have explored differences in expression levels of HLA alleles. To study the expression levels of HLA alleles more systematically we utilised two different RNA sequencing methods. Illumina RNAseq has a high sequencing accuracy and depth but is limited by the short read length, whereas Oxford Nanopore’s technology can sequence long templates, but has a poor accuracy. We studied allelic mRNA levels of HLA class I and II alleles from peripheral blood samples of 50 healthy individuals. The results demonstrate large differences in mRNA expression levels between HLA alleles. The method can be applied to quantitate the expression differences of HLA alleles in various tissues and to evaluate the role of this type of variation in transplantation matching and susceptibility to autoimmune diseases.Author SummaryEven though HLA is widely studied less is known of its allele-specific expression. Due to the pivotal role of HLA in infection response, autoimmunity, and transplantation biology its expression surely must play a part as well. In hematopoietic stem cell transplantation the challenge often is to find a suitable HLA-matched donor due to the high allelic variation. Classical HLA typing methods do not take into account HLA allele-specific expression. However, differential allelic expression levels could be crucial in finding permissive mismatches in order to save a patient’s life. Additionally, differential HLA expression levels can lead into beneficial impact in viral clearance but also undesirable effects in autoimmune diseases. To study HLA expression we developed a novel RNAseq-based method to systematically characterize allele-specific expression levels of classical HLA genes. We tested our method in a set of 50 healthy individuals and found differential expression levels between HLA alleles as well as interindividual variability at the gene level. Since NGS is already well adopted in HLA research the next step could be to determine HLA allele-specific expression in addition to HLA allelic variation and HLA-disease association studies in various cells, tissues, and diseases.
Coverage-based detection of copy number alterations in mixed samples using DNA sequencing data: a theoretical framework for evaluating statistical power
Authors: Ramdas Shweta , Pan Yanchao , Li Jun Z 
Published: September 2018

1AbstractDNA sequencing can discover not only single-base variants but also copy-number alterations (CNAs). In shotgun sequencing, regions of CNAs show step-wise changes in read depth when compared to adjacent “normal” regions, allowing their detection by parametric statistical tests that compare the mean coverage in suspected regions against that of a baseline distribution. Traditionally, the power of such a test depends on (1) the integer number of copy number change, (2) the overall sequencing depth, (3) the length of the CNA region, (4) the read length and (5) the variation of coverage along the genome, which depends on many experimental factors, including whether the chosen platform is whole-genome, whole-exome, or targeted-panel sequencing. In cases involving inadvertent sample mixing or genuine somatic mosaicism, power also depends on the mixing ratio. However, the analysis of statistical power that considers the interplay of all these factors has not been systematically developed. Here we present a general analytical framework and a series of simulations that explore situations from the simplest to the increasingly multifactorial. Specifically, we expand the expression of power to include not just the known factors but also one or both of two complications: (1) the dispersion of read depth around the mean beyond the independent sampling-by-sequencing assumption, and (2) the reduced fraction of the CNA-bearing sample (“purity”) as seen in studies of intratumor heterogeneity or in clinical monitoring of minimal residual disease. We describe the analytical formula and their simplifications in special cases, and share the extendable scripts for others to perform customized power analysis using study-specific parameters. As study designs vary and technologies continue to evolve, the input data and the noise characteristics will change depending on the practical situation. We present two use cases commonly encountered in cancer research: ultra-shallow whole-genome sequencing for detecting large, chromosome-scale events, and targeted ultra-deep sequencing for surveillance of known CNAs in rare tumor clones in the task of sensitive detection of cancer relapse or metastasis. We also present an online calculator at https://shiny.med.umich.edu/apps/hanyou/CNV_Detection_Power_Calculator/.
Membrane insertion function for SUN-KASH complex revealed by high resolution analysis of yeast centrosomes
Authors: Chen Jingjing , Gardner Jennifer M. , Yu Zulin , Smith Sarah E. , McKinney Sean , Slaughter Brian D. , Unruh Jay R. , Jaspersen Sue L. 
Published: September 2018

AbstractBipolar spindle formation in yeast requires insertion of centrosomes (known as spindle pole bodies (SPBs)) into fenestrated regions of the nuclear envelope (NE). Using structured-illumination microscopy and bimolecular fluorescence complementation, we map protein distribution at SPB fenestra and interrogate protein-protein interactions with high spatial resolution. We find that the Sad1-UNC-84 (SUN) protein Mps3 forms a ring-like structure around the SPB, similar to toroids seen for components of the SPB insertion network (SPIN). Mps3 and the SPIN component Mps2 (a Klarsicht-ANC-1-Syne-1 domain (KASH)-like protein) form a novel non-canonical linker of nucleoskeleton and cytoskeleton (LINC) complex that is connected in both luminal and extraluminal domains. This hairpin-like LINC complex forms during SPB insertion, suggesting it functions in NE reorganization at the pore membrane. The LINC complex also controls the distribution of a soluble SPIN component Bbp1. Taken together our work shows that Mps3 is a fifth SPIN component and suggests both direct and indirect roles for the LINC complex in NE remodeling.
Transsaccadic feature interactions in multiple reference frames: an fMRIa study
Authors: Baltaretu Bianca R. , Dunkley Benjamin T. , Monaco Simona , Chen Ying , Crawford J.Douglas 
Published: September 2018

AbstractTranssaccadic integration of visual features can operate in various frames of reference, but the corresponding neural mechanisms have not been differentiated. A recent fMRIa (adaptation) study identified two cortical regions in supramarginal gyrus (SMG) and extrastriate cortex that were sensitive to transsaccadic changes in stimulus orientation (Dunkley et al., 2016). Here, we modified this paradigm to identify the neural correlates for transsaccadic comparison of object orientations in: 1) Spatially Congruent (SC), 2) Retinally Congruent (RC) or 3) Spatially Incongruent (SI)) coordinates. Functional data were recorded from 12 human participants while they observed a grating (oriented 45° or 135°) before a saccade, and then judged whether a post-saccadic grating (in SC, RC, or SI configuration) had the same or different orientation. Our analysis focused on areas that showed a significant repetition suppression (Different > Same) or repetition enhancement (Same > Different) BOLD responses. Several cortical areas were significantly modulated in all three conditions: premotor/motor cortex (likely related to the manual response), and posterior-middle intraparietal sulcus. In the SC condition, uniquely activated areas included left SMG and left lateral occipitotemporal gyrus (LOtG). In the RC condition, unique areas included inferior frontal gyrus and the left lateral BA 7. In the SI condition, uniquely activated areas included the frontal eye field, medial BA 7, and right LOtG. Overall, the SC results were significantly different from both RC and SI. These data suggest that different cortical networks are used to compare pre- and post-saccadic orientation information, depending on the spatial nature of the task.Significance StatementEvery time one makes a saccade, the brain must compare and integrate stored visual information with new information. It has recently been shown that ‘transsaccadic integration’ of visual object orientation involves specific areas within parietal and occipital cortex (Dunkley et al., 2016). Here, we show that this pattern of cortical activation also depends on the spatial nature of the task: when the visual object is fixed relative to space, the eye, or relative to neither space nor the eye, different frontal, parietal, and occipital regions are engaged. More generally, these findings suggest that different aspects of trans-saccadic integration flexibly employ different cortical networks.
C57BL/6 substrain differences in inflammatory and neuropathic nociception and genetic mapping of a major quantitative trait locus underlying acute thermal nociception
Authors: Bryant Camron D. , Bagdas Deniz , Goldberg Lisa R. , Khalefa M. Tala , Reed M.Eric R. , Kirkpatrick Stacey L. , Kelliher Julia C. , Chen Melanie M. , Johnson William E. , Mulligan Megan K. , Damaj M. Imad 
Published: September 2018

ABSTRACTSensitivity to different pain modalities has a genetic basis that remains largely unknown. Employing closely related inbred mouse substrains can facilitate gene mapping of nociceptive behaviors in preclinical pain models. We previously reported enhanced sensitivity to acute thermal nociception in C57BL/6J (B6J) versus C57BL/6N (B6N) substrains. Here, we expanded on nociceptive phenotypes and observed an increase in formalin-induced inflammatory nociceptive behaviors and paw diameter in B6J versus B6N mice (Charles River Laboratories). No strain differences were observed in mechanical or thermal hypersensitivity or in edema following the Complete Freund’s Adjuvant (CFA) model of inflammatory pain, indicating specificity in the inflammatory nociceptive stimulus. In the chronic nerve constriction injury (CCI), a model of neuropathic pain, no strain differences were observed in baseline mechanical threshold or in mechanical hypersensitivity up to one month post-CCI. We replicated the enhanced thermal nociception in the 52.5°C hot plate test in B6J versus B6N mice from The Jackson Laboratory. Using a B6J x B6N-F2 cross (N=164), we mapped a major quantitative trait locus (QTL) underlying hot plate sensitivity to chromosome 7 that peaked at 26 Mb (LOD=3.81, p<0.01; 8.74 Mb-36.50 Mb) that was more pronounced in males. Genes containing expression QTLs (eQTLs) associated with the peak nociceptive marker that are implicated in pain and inflammation include Ryr1, Cyp2a5, Pou2f2, Clip3, Sirt2, Actn4, and Ltbp4 (FDR < 0.05). Future studies involving positional cloning and gene editing will determine the quantitative trait gene(s) and potential pleiotropy of this locus across pain modalities.
Characterisation and development of aspirin inducible biosensors inE. coliNissle 1917 and SimCells
Authors: Chen Jack Xiaoyu , Steel Harrison , Wu Yin-Hu , Wang Yun , Xu Jiabao , Rampley Cordelia P. N. , Thompson Ian P. , Papachristodoulou Antonis , Huang Wei E. 
Published: September 2018

AbstractA simple aspirin-inducible system has been developed by employing the Psalpromoter and SalR regulation system originally fromAcinetobacter baylyiADP1, which has been cloned intoE. colifor characterisation of gene circuits and induction of novel SimCells (simple cells). Mutagenesis at the DNA binding domain (DBD) and chemical recognition domain (CRD) of the SalR protein inA. baylyiADP1 suggests that inactive SalRican compete with activated SalRa, occupying the binding position of Psalpromoter. The induction of the Psalpromoter was compared in two different designs inE. coli: simple regulation (SRS) and positive autoregulated system (PAR). Both regulatory systems were induced in a dose-dependent manner in the presence of aspirin in the range of 0.05-10 μM. Over-expression of SalR in the SRS system reduces both baseline leakiness and inducible strength of Psalpromoter. A weak SalR expression significantly improve the inducible strength, which is in a good agreement of the proposed hypothesis of SalRi/SalRacompetitive binding. The PAR system provides a feedback loop that fine-tunes the level of SalR, displaying inducible strength. A mathematical model based on SalRi/SalRacompetitive binding hypothesis was developed, which not only reproduces the observed experimental results but also predict the performance of a new gene circuit design. The aspirin-inducible systems were also functional in probiotic strainE.coliNissle 1917 (EcN) and SimCells produced fromE. coliMC1000 ΔminD. The well-characterised and modularised aspirin-inducible gene circuits would be useful biobricks for bacterial therapy in environment and medical applications.
Factor cooperation for chromosome discrimination in Drosophila
Authors: Albig Christian , Tikhonova Evgeniya , Krause Silke , Maksimenko Oksana , Regnard Catherine , Becker Peter B. 
Published: September 2018

AbstractTranscription regulators select their genomic binding sites from a large pool of similar, non-functional sequences. Although general principles that allow such discrimination are known, the complexity of DNA elements often precludes a prediction of functional sites.The process of dosage compensation in Drosophila allows exploring the rules underlying binding site selectivity. The male-specific-lethal (MSL) Dosage Compensation Complex selectively binds to some 300 X-chromosomal ‘High Affinity Sites’ (HAS) containing GA-rich ‘MSL recognition elements’ (MREs), but disregards thousands of other MRE sequences in the genome. The DNA-binding subunit MSL2 alone identifies a subset of MREs, but fails to recognize most MREs within HAS. The ‘Chromatin-linked adaptor for MSL proteins’ (CLAMP) also interacts with many MREs genome-wide and promotes DCC binding to HAS. Using genome-wide DNA-immunoprecipitation we describe extensive cooperativity between both factors, depending on the nature of the binding sites. These are explained by physical interaction between MSL2 and CLAMP. In vivo, both factors cooperate to compete with nucleosome formation at HAS. The male-specific MSL2 thus synergises with a ubiquitous GA-repeat binding protein for refined X/autosome discrimination.
Numerical study of heat transfer performance in a pipe partially filled with non-uniform porous media under LTNE condition
Authors: Saberinejad Hojjat , Keshavarz Ali , Payandehdoost Mohammad , Azmoodeh Mohammad Reza , Batooei Alireza 
Published: September 2018

Purpose
The purpose of this paper is to numerically investigate the heat transfer enhancement in a tube filled partially with porous media under non-uniform porosity distribution and thermal dispersion effects. The optimum porous thickness ratio [R_(r,Nu)] for the heat transfer enhancement under these conditions with and without considering required pumping power is evaluated.

Design/methodology/approach
The local thermal non-equilibrium and Darcy–Brinkman–Forchheimer models are used to simulated thermal and flow fields in porous region. The tube wall and flow regime are assumed to be isothermal and laminar, respectively. The impacts of Darcy number (Da = 10-6 - 10-1) and inertia parameter (F = 0 − 2) on the Nusselt number and friction factor are studied for non-uniform porosity distribution.

Findings
First, the effect of Nusselt number indicates that there are two different behaviors with respect to uniform and non-uniform porosity for partially and fully filled porous pipe. Second, variable porosity in porous region has significant influence on the optimum thickness ratio with considering required pumping power. For negligible inertia term, it depends on the Darcy number, whereas it is 0.9 at F > 1. Third, the plug flow assumption cannot be valid even at lower Darcy number under non-uniform porosity, while this assumption is applicable at Da < 10-3 for constant porosity distribution in porous region.

Originality/value
According to the best knowledge of authors, the optimum porous thickness ratio for the heat transfer enhancement considering the pressure loss effects under variable porosity has not reported up to now. Also the plug flow assumption in such physics is not discussed.