bluuebunny/crossref_metadata_2025_split huggingface dataset:
Apremilast increases IL-10-producing regulatory B cells and decreases proinflammatory T cells and innate cells in psoriatic arthritis and psoriasis
Authors: Mavropoulos Athanasios , Zafiriou Efterpi , Simopoulou Theodora , Brotis Alexandros G , Liaskos Christos , Roussaki-Schulze Aggeliki , Katsiari Christina G , Bogdanos Dimitrios P , Sakkas Lazaros I 
Published: May 2019

Abstract

Objectives
Psoriatic arthritis (PsA) and psoriasis are immune-mediated inflammatory diseases sharing common immunological mechanisms. Regulatory B cells (Breg cells) producing IL–10 (B10 cells), a critical anti-inflammatory B-cell subset, were found to be decreased in both PsA and psoriasis. Apremilast, a phosphodiesterase-4(PDE4) inhibitor, increases IL-10 and therefore, we examined the effect of apremilast on Breg cells.

Methods
Fifty patients, including 20 with PsA and 30 with psoriasis, were included in the study. The effect of apremilast on Breg cells at 3, 6 and 12 months post-treatment, was examined by flow cytometry in ODN2006 (TLR9)-stimulated peripheral blood mononuclear cells and magnetically-isolated cells. Th1 cells, Th17 cells and NKT were also measured.

Results
Ex vivo stimulated cell analysis identified that post-apremilast (IL-10+CD19+) B10 cells were increased in all PsA and psoriasis patients and correlated with psoriatic skin and joint clinical improvement. Apremilast decreased IFNγ(+) T and NKT cells and IL-17(+)NKT cells. B10 cells also inversely correlated with Th1 cells, and IFNγ(+)NKT cells.

Conclusion
These results suggest that Breg cells are a major target of apremilast in PsA and psoriasis and that apremilast-induced increase of Breg cells is associated with a decrease of Th1 cells, IFNγ-producing NKT cells and IL-17-producing NKT cells.
DEVElOPMENT OF DOSE ESTIMATION SYSTEM INTEGRATING SEDIMENT MODEL FOR RECYCLING RADIOCESIUM-CONTAMINATED SOIL TO COASTAL RECLAMATION
Authors: Miwa Kazuji , Takeda Seiji , Iimoto Takeshi 
Published: May 2019

Abstract
We have developed a dose estimation system integrating assessment methods of radionuclide dispersion in ocean for the case of recycling radiocesium-contaminated soil to coastal reclamation. Radionuclide dispersion in ocean is assessed considering dissolved radionuclide and adsorbed radionuclide on particle by sediment model (OECD/NEA). Time series of Cs-137 dispersion at Fukushima coastal area is assessed by the sediment model and result is almost same with measured value. The major exposure pathways in recycling are estimated by using result of radiocesium dispersion assessment, and internal exposure dose by marine products ingestion is sufficiently lower than external exposure dose of worker.
Universal and naked-eye gene detection platform based on CRISPR/Cas12a/13a system
Authors: Yuan Chao-Qun , Tian Tian , Sun Jian , Hu Meng-Lu , Wang Xu-Sheng , Xiong Er-Hu , Cheng Meng , Bao Yi-Juan , Lin Wei , Jiang Jie-Ming , Yang Cheng-Wei , Chen Qian , Wang Heng , Wang Xi-Ran , Deng Xian-Bo , Liao Xiao-Ping , Liu Ya-Hong , Zhang Gui-Hong , Zhou Xiao-Ming 
Published: May 2019

AbstractColorimetric gene detection based on gold nanoparticles (AuNPs) is an attractive detection format due to its simplicity. Here, we report a new design for a colorimetric gene-sensing platform based on the CRISPR/Cas system that has improved specificity, sensitivity, and universality. CRISPR/Cas12a and CRISPR/Cas13a have two distinct catalytic activities and are used for specific target gene recognition. Programmable recognition of DNA by Cas12a/crRNA and RNA by Cas13a/crRNA with a complementary sequence activates the nonspecific trans-ssDNA or -RNA cleavage, respectively, thus degrading the ssDNA or RNA linkers which are designed as a hybridization template for the AuNP-DNA probe pair. Target-induced trans -ssDNA or RNA cleavage leads to a distance-dependent color change for the AuNP-DNA probe pair. In this platform, naked eye detection of transgenic rice, African swine fever virus (ASFV), and a miRNA can be completed within 1 hour. Our colorimetric gene-sensing method shows superior characteristics, such as probe universality, isothermal reaction conditions, on-site detection capability, and sensitivity that is comparable to that of the fluorescent detection; thus, this method represents a robust next generation gene detection platform.
Influence of nanopillar arrays on fibroblast motility, adhesion and migration mechanisms
Authors: Beckwith Kai S. , Ullmann Sindre , Vinje Jakob , Sikorski Pawel 
Published: May 2019

AbstractSurfaces decorated with high aspect ratio nanostructures are a promising tool to study cellular processes and design novel devices to control cellular behaviour, perform intracellular sensing or deliver effector molecules to cells in culture. However, little is known about the dynamics of cellular phenomenon such as adhesion, spreading and migration on such surfaces. In particular, how these are influenced by the surface properties. In this work, we investigate fibroblast behaviour on regular arrays of 1 micrometer high, polymer nanopillars with varying pillar to pillar distance (array pitch). NIH-3T3 fibroblasts spread on all arrays, and on contact with the substrate engulf nanopillars independently of the array pitch. As the cells start to spread, different behaviour is observed. On dense arrays which have the pitch equal or below 1 micrometer, cells are suspended on top of the nanopillars, making only sporadic contact with the glass support. Cells stay attached to the glass support and fully engulf nanopillars during spreading and migration on the sparse arrays which are characterized by a pitch of 2 micrometers and above. These alternate states have a profound effect on cell migration rates, which are strongly reduced on nanopillar sparse arrays. Dynamic actin puncta colocalize with nanopillars during cell spreading and migration. Strong membrane association with engulfed nanopillars might explain the reduced migration rates on sparse arrays. This work reveals several interesting phenomenon of dynamical cell behaviour on nanopillar arrays, and provides important perspectives on design and applications of high aspect ratio nanostructures.
Transcriptomic evidence that von Economo neurons are regionally specialized extratelencephalic-projecting excitatory neurons
Authors: Hodge Rebecca D , Miller Jeremy A , Novotny Mark , Kalmbach Brian E , Ting Jonathan T , Bakken Trygve E , Aevermann Brian D , Barkan Eliza R , Berkowitz-Cerasano Madeline L , Cobbs Charles , Diez-Fuertes Francisco , Ding Song-Lin , McCorrison Jamison , Schork Nicholas J , Shehata Soraya I , Smith Kimberly A , Sunkin Susan M , Tran Danny N , Venepally Pratap , Yanny Anna Marie , Steemers Frank J , Phillips John W , Bernard Amy , Koch Christof , Lasken Roger S , Scheuermann Richard H , Lein Ed S 
Published: May 2019

Abstractvon Economo neurons (VENs) are bipolar, spindle-shaped neurons restricted to layer 5 of human frontoinsula and anterior cingulate cortex that appear to be selectively vulnerable to neuropsychiatric and neurodegenerative diseases, although little is known about other VEN cellular phenotypes. Single nucleus RNA-sequencing of frontoinsula layer 5 identified a transcriptomically-defined cell cluster that contained VENs, but also fork cells and a subset of pyramidal neurons. Cross-species alignment of this cell cluster with a well-annotated mouse classification shows strong homology to extratelencephalic (ET) excitatory neurons that project to subcerebral targets. This cluster also shows strong homology to a putative ET cluster in human temporal cortex, but with a strikingly specific regional signature. Together these results predict VENs are a regionally distinctive type of ET neuron, and we additionally describe the first patch clamp recordings of VENs from neurosurgically-resected tissue that show distinctive intrinsic membrane properties relative to neighboring pyramidal neurons.
Pilot study of EVIDENCE: High diagnostic yield and clinical utility of whole exome sequencing using an automated interpretation system for patients with suspected genetic disorders
Authors: Seo Go Hun , Kim Taeho , Park Jung-young , Lee Jungsul , Kim Sehwan , Won Dhong-gun , Oh Arum , Lee Yena , Choi In Hee , Choi Jeongmin , Lee Hajeong , Kang Hee Gyung , Cho Hee Yeon , Cho Min Hyun , Kim Yoon Jeon , Yoon Young Hee , Eun Baik-Lin , Desnick Robert J , Keum Changwon , Lee Beom Hee 
Published: May 2019

AbstractPurposeEVIDENCE, an automated interpretation system, has been developed to facilitate the entire process of whole exome sequencing (WES) analyses. This study investigated the diagnostic yield of EVIDENCE in patients suspected genetic disorders.MethodsDNA from 330 probands (age range, 0–68 years) with suspected genetic disorders were subjected to WES. Candidate variants were identified by EVIDENCE and confirmed by testing family members and/or clinical reassessments.ResultsThe average number of overlapping organ categories per patient was 4.5 ± 5.0. EVIDENCE reported a total 244 variants in 215 (65.1%) of the 330 probands. After clinical reassessment and/or family member testing, 196 variants were identified in 171 probands (51.8%), including 115 novel variants. These variants were confirmed as being responsible for 146 genetic disorders. One hundred-seven (54.6%) of the 196 variants were categorized as pathogenic or likely pathogenic before, and 146 (74.6%) after, clinical assessment and/or family member testing. Factors associated with a variant being confirmed as causative include rules, such as PVS1, PS1, PM1, PM5, and PP5, and similar symptom scores between that variant and a patient’s phenotype.ConclusionThis new, automated variant interpretation system facilitated the diagnosis of various genetic diseases with a 51% improvement in diagnostic yield.
Using selection by non-antibiotic stressors to sensitize bacteria to antibiotics
Authors: Maltas Jeff , Krasnick Brian , Wood Kevin B. 
Published: May 2019

ABSTRACTBacterial resistance to one antibiotic is frequently accompanied by crossresistance to other drugs. Similarly, non-antibiotic selective forces, from biocides to osmotic stress, have been shown to decrease antibiotic susceptibility, often the result of shared, non-specific resistance mechanisms. On the other hand, evolved resistance to particular antibiotics may also be associated with increased sensitivity to other drugs, highlighting evolutionary constraints that could form the basis for novel anti-resistance strategies. While recent studies indicate this collateral sensitivity is common between antibiotics, much less is known about potentially sensitizing effects of non-antibiotic stressors. In this study, we use laboratory evolution to investigate adaptation of E. faecalis, an opportunistic bacterial pathogen, to a broad collection of environmental agents, ranging from antibiotics and biocides to extreme pH and osmotic stress. We find that non-antibiotic selection frequently leads to increased sensitivity to other conditions, including multiple antibiotics. Using population sequencing and whole genome sequencing of single isolates from the evolved populations, we identify multiple mutations in genes previously linked with resistance to the selecting conditions, including genes corresponding to known drug targets or multi-drug efflux systems previously tied to collateral sensitivity. Finally, we hypothesized based on the measured sensitivity profiles that sequential rounds of antibiotic and non-antibiotic selection may lead to hypersensitive populations by harnessing the orthogonal collateral effects of particular pairs of selective forces. To test this hypothesis, we show experimentally that populations evolved to a sequence of linezolid (an oxazolidinone antibiotic) and sodium benzoate (a common preservative) exhibit increased sensitivity to more stressors than adaptation to either condition alone. The results demonstrate how sequential adaptation to drug and non-drug environments can be used to sensitize bacterial to antibiotics and highlight new potential strategies for exploiting shared constraints governing adaptation to diverse environmental challenges.
Linking patterns of genetic variation to processes of diversification in Malaysian torrent frogs (Anura: Ranidae:Amolops): a landscape genomics approach
Authors: Chan Kin Onn , Brown Rafe M. 
Published: May 2019

ABSTRACTThe interplay between environmental attributes and evolutionary processes can provide valuable insights into how biodiversity is generated, partitioned, and distributed. This study investigates the role of spatial, environmental, and historical factors that could potentially drive diversification and shape genetic variation in Malaysian torrent frogs. Torrent frogs are ecologically conserved, and we hypothesize that this could impose tight constraints on dispersal routes, gene flow, and consequently genetic structure. Moreover, levels of gene flow were shown to vary among populations from separate mountain ranges, indicating that genetic differentiation could be influenced by landscape features. Using genome-wide SNPs in conjunction with landscape variables derived from GIS, we performed distance-based redundancy analyses and variance partitioning to disentangle the effects of isolation-by-distance (IBD), isolation-by-environment (IBE), and isolation-by-colonization (IBC). Our results demonstrated that IBE, contributed minimally to genetic variation. Intraspecific population structure can be largely attributed to IBD, whereas interspecific diversification was primarily driven by IBC. We also detected two distinct population bottlenecks, indicating that speciation events were likely driven by vicariance or founder events.
Toffee – a highly efficient, lossless file format for DIA-MS
Authors: Tully Brett 
Published: May 2019

ABSTRACTThe closed nature of vendor file formats in mass spectrometry is a significant barrier to progress in developing robust bioinformatics software. In response, the community has developed the open mzML format, implemented in XML and based on controlled vocabularies. Widely adopted, mzML is an important step forward; however, it suffers from two challenges that are particularly apparent as the field moves to high-throughput proteomics: large increase in file size, and a largely sequential I/O access pattern.Described here is ‘toffee’, an open, random I/O format backed by HDF5, with lossless compression that gives file sizes similar to the original vendor format and can be reconverted back to mzML without penalty. It is shown that mzML and toffee are equivalent when processing data using OpenSWATH algorithms, in additional to novel applications that are enabled by new data access patterns. For instance, a peptide-centric deep-learning pipeline for peptide identification is proposed.Documentation and examples are available at https://toffee.readthedocs.io, and all code is MIT licensed at https://bitbucket.org/cmriprocan/toffee.
The female urinary microbiota in relation to the reproductive tract microbiota
Authors: Chen Chen , Hao Lilan , Wei Weixia , Li Fei , Song Liju , Zhang Xiaowei , Dai Juanjuan , Jie Zhuye , Li Jiandong , Song Xiaolei , Wang Zirong , Zhang Zhe , Zeng Liping , Du Hui , Tang Huiru , Yang Huanming , Wang Jian , Kristiansen Karsten , Xu Xun , Wu Ruifang , Jia Huijue 
Published: May 2019

AbstractHuman urine is traditionally considered to be sterile, and whether the urine harbours distinct microbial communities has been a matter of debate. The potential link between female urine and reproductive tract microbial communities is currently not clear.Here we collected the urine samples from 147 Chinese women of reproductive age, and explored the nature of colonization by 16S rRNA gene amplicon sequencing, real-time qPCR and live bacteria culture. To demonstrate utility intra-individual Spearman’s correlation was used to explore the relationship between urine and multi-sites of the reproductive tract. PERMANOVA was also performed to explore potential correlations between the lifestyle and various clinical factors and urinary bacterial communities. Our data demonstrated distinct bacterial communities in urine, indicative of a non-sterile environment. Types of diverse, Streptococcus-dominated, and Lactobacillus-dominated were the three most common types in the cohort. Detailed comparison of the urinary microbiota to the multi-sites of reproductive tract microbiota demonstrated the urinary microbiota was more similar to the microbiota in the cervix and uterine cavity instead of vagina in the same women.Our data demonstrates the potential connectivity of the microbiota in the female urogenital system and provided insight into the exploration of urethra and genital tract diseases.
Electrospun Ag-doped SnO2 hollow nanofibers with high antibacterial activity
Authors: Li Yang , Tang Xiaoning , Zhang Bin , Mao Huaming 
Published: May 2019

AbstractWith the continuous improvement in medical science in modern times, the spread of bacterial infection has become a matter of global concern. Therefore, the search for biological medical materials with antibacterial function has become a focus of intense research. In this work, pure SnO2 and Ag-doped SnO2 hollow nanofibers were fabricated by a combination of an electrospinning method and a calcination procedure, and the effects of the doped Ag on antibacterial activity were subsequently investigated. Through the process of high-temperature calcination, a high heating rate would lead to the formation of a hollow tubular structure in SnO2 fibers, and Ag2O would be reduced to Ag0 by a facile process with appropriate thermal treatment. Additionally, the existence of SnO2 as a tetragonal rutile structure was confirmed. On the basis of pure SnO2, doping with silver greatly improved the antibacterial activity of hollow nanofibers. The formation mechanism and the antibacterial mechanism of pure SnO2 and Ag-doped hollow nanofibers are also discussed. This study has broad application prospects for biological medicine.
Mycobacterium tuberculosis reactivates HIV via exosomes mediated resetting of cellular redox potential and bioenergetics
Authors: Tyagi Priyanka , Pal Virender Kumar , Srinivasan Sandhya , Singh Amit 
Published: May 2019

AbstractThe synergy betweenMycobacterium tuberculosis(Mtb) and HIV-1 interferes with therapy and facilitates pathogenesis of both human pathogens. Fundamental mechanisms by whichMtbexacerbates HIV-1 are not clear. Here, we show that exosomes secreted by macrophages infected withMtb, including drug-resistant clinical strains, reactivate HIV-1 by inducing oxidative stress. Mechanistically,Mtb-specific exosomes realign mitochondrial and non-mitochondrial oxygen consumption rate (OCR) and modulates the expression of genes mediating oxidative stress response, inflammation, and HIV-1 transactivation. Proteomics revealed the enrichment of several host factors (e.g.,HIF-1α, galectins, Hsp90) known to promote HIV-1 reactivation in theMtb-specific exosomes. Treatment with a known antioxidant, N-acetyl cysteine, or with the inhibitors of host factors galectins and Hsp90 attenuated HIV-1 reactivation byMtb-specific exosomes. Our findings uncovered new paradigms for understanding the redox and bioenergetics basis of HIV-TB co-infection, which will enable the design of effective therapeutic strategies.
Draft Genome Sequence of Candida auris Strain LOM, a Human Clinical Isolate from Greater Metropolitan Houston, Texas
Authors: Long S. Wesley , Olsen Randall J. , Nguyen Hoang A. T. , Saavedra Matthew Ojeda , Musser James M. 
Published: May 2019

ABSTRACTCandida auris is an emerging pathogen with considerable public health importance. We present the draft genome sequence of a strain recently cultured from the urine of a patient hospitalized in the greater Houston metropolitan region. Two combined Oxford Nanopore sequencing runs provided sufficient data to rapidly generate a draft genome.
Evaluating the performance of 3-tissue constrained spherical deconvolution pipelines for within-tumor tractography
Authors: Aerts Hannelore , Dhollander Thijs , Marinazzo Daniele 
Published: May 2019

AbstractThe use of diffusion MRI (dMRI) for assisting in the planning of neurosurgery has become increasingly common practice, allowing to non-invasively map white matter pathways via tractography techniques. Limitations of earlier pipelines based on the diffusion tensor imaging (DTI) model have since been revealed and improvements were made possible by constrained spherical deconvolution (CSD) pipelines. CSD allows to resolve a full white matter (WM) fiber orientation distribution (FOD), which can describe so-called “crossing fibers”: complex local geometries of WM tracts, which DTI fails to model. This was found to have a profound impact on tractography results, with substantial implications for presurgical decision making and planning. More recently, CSD itself has been extended to allow for modeling of other tissue compartments in addition to the WM FOD, typically resulting in a 3-tissue CSD model. It seems likely this may improve the capability to resolve WM FODs in the presence of infiltrating tumor tissue. In this work, we evaluated the performance of 3-tissue CSD pipelines, with a focus on within-tumor tractography. We found that a technique named single-shell 3-tissue CSD (SS3T-CSD) successfully allowed tractography within infiltrating gliomas, without increasing existing single-shell dMRI acquisition requirements.
Organohalide-respiringDesulfolunaspecies isolated from marine environments
Authors: Peng Peng , Goris Tobias , Lu Yue , Nijsse Bart , Burrichter Anna , Schleheck David , Koehorst Jasper J. , Liu Jie , Sipkema Detmer , Sinninghe Damste Jaap S. , Stams Alfons J. M. , Häggblom Max M. , Smidt Hauke , Atashgahi Siavash 
Published: May 2019

AbstractThe genusDesulfolunacomprises two anaerobic sulfate-reducing strains,D. spongiiphilaAA1⊤andD. butyratoxydansMSL71⊤of which only the former was shown to perform organohalide respiration (OHR). Here we isolated a third member of this genus from marine intertidal sediment, designedD. spongiiphilastrain DBB. All threeDesulfolunastrains harbour three reductive dehalogenase gene clusters (rdhABC) and corrinoid biosynthesis genes in their genomes. Brominated but not chlorinated aromatic compounds were dehalogenated by all three strains. TheDesulfolunastrains maintained OHR in the presence of 20 mM sulfate or 20 mM sulfide, which often negatively affect OHR. Strain DBB sustained OHR with 2% oxygen in the gas phase, in line with its genetic potential for reactive oxygen species detoxification. Reverse transcription-quantitative PCR (RT-qPCR) revealed differential induction ofrdhAgenes in strain DBB in response to 1,4-dibromobenzene or 2,6-dibromophenol. Proteomic analysis confirmed differential expression ofrdhA1with 1,4-dibromobenzene, and revealed a possible electron transport chain from lactate dehydrogenases and pyruvate oxidoreductase to RdhA1 via menaquinones and either RdhC, or Fix complex (electron transfer flavoproteins), or Qrc complex (Type-1 cytochrome c3:menaquinone oxidoreductase).