bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenotypic high-throughput screening platform identifies novel chemotypes for necroptosis inhibition
Authors: Brito Hugo , Marques Vanda , Afonso Marta B. , Brown Dean G. , Börjesson Ulf , Selmi Nidhal , Smith David M. , Roberts Ieuan O. , Fitzek Martina , Aniceto Natália , Guedes Rita C. , Moreira Rui , Rodrigues Cecília M. P.
Published: February 2020

Regulated necrosis or necroptosis, mediated by receptor-interacting kinase 1 (RIPK1), RIPK3 and pseudokinase mixed lineage kinase domain-like protein (MLKL), contributes to the pathogenesis of inflammatory, infectious and degenerative diseases. Recently identified necroptosis inhibitors display moderate specificity, suboptimal pharmacokinetics, off-target effects and toxicity, preventing these molecules from reaching the clinic. Here, we developed a cell-based high-throughput screening (HTS) cascade for the identification of small-molecule inhibitors of necroptosis. From the initial library of over 250,000 compounds, the primary screening phase identified 356 compounds that strongly inhibited TNF-α-induced necroptosis, but not apoptosis, in human and murine cell systems, with EC50 < 6.7 μM. From these, 251 compounds were tested for RIPK1 and/or RIPK3 kinase inhibitory activity; some were active and several have novel mechanisms of action. Based on specific chemical descriptors, 110 compounds proceeded into the secondary screening cascade, which then identified seven compounds with maximum ability to reduce MLKL activation, IC50 >100 μM, EC50 2.5–11.5 μM under long-term necroptosis execution in murine fibroblast L929 cells, and full protection from ATP depletion and membrane leakage in human and murine cells. As a proof of concept, compound SN-6109, with binding mode to RIPK1 similar to that of necrostatin-1, confirmed RIPK1 inhibitory activity and appropriate pharmacokinetic properties. SN-6109 was further tested in mice, showing efficacy against TNF-α-induced systemic inflammatory response syndrome. In conclusion, a phenotypic-driven HTS cascade promptly identified robust necroptosis inhibitors with in vivo activity, currently undergoing further medicinal chemistry optimization. Notably, the novel hits highlight the opportunity to identify new molecular mechanisms of action in necroptosis.
A computational platform for high-throughput analysis of RNA sequences and modifications by mass spectrometry
Authors: Wein Samuel , Andrews Byron , Sachsenberg Timo , Santos-Rosa Helena , Kohlbacher Oliver , Kouzarides Tony , Garcia Benjamin A. , Weisser Hendrik
Published: February 2020

The field of epitranscriptomics continues to reveal how post-transcriptional modification of RNA affects a wide variety of biological phenomena. A pivotal challenge in this area is the identification of modified RNA residues within their sequence contexts. Mass spectrometry (MS) offers a comprehensive solution by using analogous approaches to shotgun proteomics. However, software support for the analysis of RNA MS data is inadequate at present and does not allow high-throughput processing. Existing software solutions lack the raw performance and statistical grounding to efficiently handle the numerous modifications found on RNA. We present a free and open-source database search engine for RNA MS data, called NucleicAcidSearchEngine (NASE), that addresses these shortcomings. We demonstrate the capability of NASE to reliably identify a wide range of modified RNA sequences in four original datasets of varying complexity. In human tRNA, we characterize over 20 different modification types simultaneously and find many cases of incomplete modification.
Inhibiting WNT and NOTCH in renal cancer stem cells and the implications for human patients
Authors: Fendler Annika , Bauer Daniel , Busch Jonas , Jung Klaus , Wulf-Goldenberg Annika , Kunz Severine , Song Kun , Myszczyszyn Adam , Elezkurtaj Sefer , Erguen Bettina , Jung Simone , Chen Wei , Birchmeier Walter
Published: February 2020

Current treatments for clear cell renal cell cancer (ccRCC) are insufficient because two-thirds of patients with metastases progress within two years. Here we report the identification and characterization of a cancer stem cell (CSC) population in ccRCC. CSCs are quantitatively correlated with tumor aggressiveness and metastasis. Transcriptional profiling and single cell sequencing reveal that these CSCs exhibit an activation of WNT and NOTCH signaling. A significant obstacle to the development of rational treatments has been the discrepancy between model systems and the in vivo situation of patients. To address this, we use CSCs to establish non-adherent sphere cultures, 3D tumor organoids, and xenografts. Treatment with WNT and NOTCH inhibitors blocks the proliferation and self-renewal of CSCs in sphere cultures and organoids, and impairs tumor growth in patient-derived xenografts in mice. These findings suggest that our approach is a promising route towards the development of personalized treatments for individual patients.
Chromosomal origin of replication coordinates logically distinct types of bacterial genetic regulation
Authors: Kosmidis Kosmas , Jablonski Kim Philipp , Muskhelishvili Georgi , Hütt Marc-Thorsten
Published: February 2020

For a long time it has been hypothesized that bacterial gene regulation involves an intricate interplay of the transcriptional regulatory network (TRN) and the spatial organization of genes in the chromosome. Here we explore this hypothesis both on a structural and on a functional level. On the structural level, we study the TRN as a spatially embedded network. On the functional level, we analyze gene expression patterns from a network perspective (“digital control”), as well as from the perspective of the spatial organization of the chromosome (“analog control”). Our structural analysis reveals the outstanding relevance of the symmetry axis defined by the origin (Ori) and terminus (Ter) of replication for the network embedding and, thus, suggests the co-evolution of two regulatory infrastructures, namely the transcriptional regulatory network and the spatial arrangement of genes on the chromosome, to optimize the cross-talk between two fundamental biological processes: genomic expression and replication. This observation is confirmed by the functional analysis based on the differential gene expression patterns of more than 4000 pairs of microarray and RNA-Seq datasets for E. coli from the Colombos Database using complex network and machine learning methods. This large-scale analysis supports the notion that two logically distinct types of genetic control are cooperating to regulate gene expression in a complementary manner. Moreover, we find that the position of the gene relative to the Ori is a feature of very high predictive value for gene expression, indicating that the Ori–Ter symmetry axis coordinates the action of distinct genetic control mechanisms.
High-resolution T2-FLAIR and non-contrast CT brain atlas of the elderly
Authors: Rajashekar Deepthi , Wilms Matthias , MacDonald M. Ethan , Ehrhardt Jan , Mouches Pauline , Frayne Richard , Hill Michael D. , Forkert Nils D.
Published: February 2020

Normative brain atlases are a standard tool for neuroscience research and are, for example, used for spatial normalization of image datasets prior to voxel-based analyses of brain morphology and function. Although many different atlases are publicly available, they are usually biased with respect to an imaging modality and the age distribution. Both effects are well known to negatively impact the accuracy and reliability of the spatial normalization process using non-linear image registration methods. An important and very active neuroscience area that lacks appropriate atlases is lesion-related research in elderly populations (e.g. stroke, multiple sclerosis) for which FLAIR MRI and non-contrast CT are often the clinical imaging modalities of choice. To overcome the lack of atlases for these tasks and modalities, this paper presents high-resolution, age-specific FLAIR and non-contrast CT atlases of the elderly generated using clinical images.
Author Correction: Physical and chemical descriptors for predicting interfacial thermal resistance
Authors: Wu Yen-Ju , Zhan Tianzhuo , Hou Zhufeng , Fang Lei , Xu Yibin
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Machine Learning and Bioinformatics Models to Identify Pathways that Mediate Influences of Welding Fumes on Cancer Progression
Authors: Rana Humayan Kabir , Akhtar Mst. Rashida , Islam M. Babul , Ahmed Mohammad Boshir , Lió Pietro , Huq Fazlul , Quinn Julian M. W. , Moni Mohammad Ali
Published: February 2020

Welding generates and releases fumes that are hazardous to human health. Welding fumes (WFs) are a complex mix of metallic oxides, fluorides and silicates that can cause or exacerbate health problems in exposed individuals. In particular, WF inhalation over an extended period carries an increased risk of cancer, but how WFs may influence cancer behaviour or growth is unclear. To address this issue we employed a quantitative analytical framework to identify the gene expression effects of WFs that may affect the subsequent behaviour of the cancers. We examined datasets of transcript analyses made using microarray studies of WF-exposed tissues and of cancers, including datasets from colorectal cancer (CC), prostate cancer (PC), lung cancer (LC) and gastric cancer (GC). We constructed gene-disease association networks, identified signaling and ontological pathways, clustered protein-protein interaction network using multilayer network topology, and analyzed survival function of the significant genes using Cox proportional hazards (Cox PH) model and product-limit (PL) estimator. We observed that WF exposure causes altered expression of many genes (36, 13, 25 and 17 respectively) whose expression are also altered in CC, PC, LC and GC. Gene-disease association networks, signaling and ontological pathways, protein-protein interaction network, and survival functions of the significant genes suggest ways that WFs may influence the progression of CC, PC, LC and GC. This quantitative analytical framework has identified potentially novel mechanisms by which tissue WF exposure may lead to gene expression changes in tissue gene expression that affect cancer behaviour and, thus, cancer progression, growth or establishment.
The role of faceting and elongation on the magnetic anisotropy of magnetite Fe3O4 nanocrystals
Authors: Moreno Roberto , Poyser Samuel , Meilak Daniel , Meo Andrea , Jenkins Sarah , Lazarov Vlado K. , Vallejo-Fernandez Gonzalo , Majetich Sara , Evans Richard F. L.
Published: February 2020

Fe3O4 nanoparticles are one of the most promising candidates for biomedical applications such as magnetic hyperthermia and theranostics due to their bio-compatibility, structural stability and good magnetic properties. However, much is unknown about the nanoscale origins of the observed magnetic properties of particles due to the dominance of surface and finite size effects. Here we have developed an atomistic spin model of elongated magnetite nanocrystals to specifically address the role of faceting and elongation on the magnetic shape anisotropy. We find that for faceted particles simple analytical formulae overestimate the magnetic shape anisotropy and that the underlying cubic anisotropy makes a significant contribution to the energy barrier for moderately elongated particles. Our results enable a better estimation of the effective magnetic anisotropy of highly crystalline magnetite nanoparticles and is a step towards quantitative prediction of the heating effects of magnetic nanoparticles.
Early-life microbiota transplantation affects behavioural responses, serotonin and immune characteristics in chicken lines divergently selected on feather pecking
Authors: van der Eijk Jerine A. J. , Rodenburg T. Bas , de Vries Hugo , Kjaer Joergen B. , Smidt Hauke , Naguib Marc , Kemp Bas , Lammers Aart
Published: February 2020

Gut microbiota influences host behaviour and physiology, such as anxiety, stress, serotonergic and immune systems. These behavioural and physiological characteristics are related to feather pecking (FP), a damaging behaviour in chickens that reduces animal welfare and productivity. Moreover, high FP (HFP) and low FP (LFP) lines differed in microbiota composition. However, it is unknown whether microbiota can influence the development of FP. For the first time, we identified the effects of microbiota transplantation on FP, and behavioural and physiological characteristics related to FP. HFP and LFP chicks received sterile saline (control), HFP or LFP microbiota transplantation during the first two weeks post-hatch. Microbiota transplantation influenced behavioural responses of the HFP line during treatment and of the LFP line after treatment. In both lines, homologous microbiota transplantation (i.e., receiving microbiota from their line) resulted in more active behavioural responses. Furthermore, microbiota transplantation influenced immune characteristics (natural antibodies) in both lines and peripheral serotonin in the LFP line. However, limited effects on microbiota composition, stress response (corticosterone) and FP were noted. Thus, early-life microbiota transplantation had immediate and long-term effects on behavioural responses and long-term effects on immune characteristics and peripheral serotonin; however, the effects were dependent on host genotype. Since early-life microbiota transplantation influenced behavioural and physiological characteristics that are related to FP, it could thus influence the development of FP later in life.
Charge mobility calculation of organic semiconductors without use of experimental single-crystal data
Authors: Ishii Hiroyuki , Obata Shigeaki , Niitsu Naoyuki , Watanabe Shun , Goto Hitoshi , Hirose Kenji , Kobayashi Nobuhiko , Okamoto Toshihiro , Takeya Jun
Published: February 2020

Prediction of material properties of newly designed molecules is a long-term goal in organic electronics. In general, it is a difficult problem, because the material properties are dominated by the unknown packing structure. We present a practical method to obtain charge transport properties of organic single crystals, without use of experimental single-crystal data. As a demonstration, we employ the promising molecule C10–DNBDT. We succeeded in quantitative evaluation of charge mobility of the single crystal using our quantum wave-packet dynamical simulation method. Here, the single-crystal data is computationally obtained by searching possible packing structures from structural formula of the molecule. We increase accuracy in identifying the actual crystal structure from suggested ones by using not only crystal energy but also similarity between calculated and experimental powder X-ray diffraction patterns. The proposed methodology can be a theoretical design technique for efficiently developing new high-performance organic semiconductors, since it can estimate the charge transport properties at early stage in the process of material development.
Analysis of TET2 and EZH2 gene functions in chromosome instability in acute myeloid leukemia
Authors: Wang Jingyi , He Na , Wang Ruiqing , Tian Tian , Han Fengjiao , Zhong Chaoqin , Zhang Chen , Hua Mingqiang , Ji Chunyan , Ma Daoxin
Published: February 2020

TET2 and EZH2 play important roles in the epigenetic regulation in many cancers. However, their specific roles in acute myeloid leukemia (AML) pathogenesis remain unknown. Here, the expression, methylation or mutation of EZH2 and TET2 was determined and further correlated with the levels of the chromosome instability (CIN) genes MAD2 and CDC20. We down-regulated EZH2 and TET2 in AML cell lines and assessed the effect on CIN using fluorescence in situ hybridization (FISH). Our results showed that TET2, EZH2, MAD2 and CDC20 were aberrantly expressed in AML patients. The expression level of MAD2 or CDC20 was positively correlated with that of TET2 or EZH2. Hypermethylation of the TET2 gene down-regulated its transcription. Down-regulation of EZH2 or TET2 expression inhibited apoptosis, affected MAD2 and CDC20 expression, and promoted CIN in AML cells. Decitabine treatment restored TET2 methylation and EZH2 transcription and ameliorated CIN in AML. Therefore, TET2 and EZH2 play a tumor-inhibiting role in AML that affects CIN via MAD2 and CDC20.
Modelling of pancreatic cancer biology: transcriptomic signature for 3D PDX-derived organoids and primary cell line organoid development
Authors: Nelson Shannon R. , Zhang Chenxi , Roche Sandra , O’Neill Fiona , Swan Niall , Luo Yonglun , Larkin AnneMarie , Crown John , Walsh Naomi
Published: February 2020

With a five-year survival rate of 9%, pancreatic ductal adenocarcinoma (PDAC) is the deadliest of all cancers. The rapid mortality makes PDAC difficult to research, and inspires a resolve to create reliable, tractable cellular models for preclinical cancer research. Organoids are increasingly used to model PDAC as they maintain the differentiation status, molecular and genomic signatures of the original tumour. In this paper, we present novel methodologies and experimental approaches to develop PDAC organoids from PDX tumours, and the simultaneous development of matched primary cell lines. Moreover, we also present a method of recapitulating primary cell line cultures to organoids (CLOs). We highlight the usefulness of CLOs as PDAC organoid models, as they maintain similar transcriptomic signatures as their matched patient-derived organoids and patient derived xenografts (PDX)s. These models provide a manageable, expandable in vitro resource for downstream applications such as high throughput screening, functional genomics, and tumour microenvironment studies.
Chemically labeled toxins or bioactive peptides show a heterogeneous intracellular distribution and low spatial overlap with autofluorescence in bloom-forming cyanobacteria
Authors: Kurmayer Rainer , Entfellner Elisabeth , Weisse Thomas , Offterdinger Martin , Rentmeister Andrea , Deng Li
Published: February 2020

Harmful algal blooms formed by colony-forming cyanobacteria deteriorate water resources by producing cyanotoxins, which frequently occur at high intracellular concentrations. We aimed to localize toxic microcystins (MCs) and bioactive anabaenopeptins (APs) at the subcellular level under noninvasive conditions. Since both metabolites are synthesized nonribosomally, the relaxed specificity of key enzymes catalyzing substrate activation allowed chemical labeling through a standard copper-catalyzed click chemistry reaction. The genera Planktothrix and Microcystis specifically incorporated unnatural amino acids such as N-propargyloxy-carbonyl-L-lysine or O-propargyl-L-tyrosine, resulting in modified AP or MC peptides carrying the incorporated alkyne moiety. The labeled cells were quantitatively differentiated from the unlabeled control cells. MCs and APs occurred intracellularly as distinct entities showing a cell-wide distribution but a lowered spatial overlap with natural autofluorescence. Using the immunofluorescence technique, colocalization with markers of individual organelles was utilized to relate the distribution of labeled MCs to cellular compartments, e.g., using RbcL and FtsZ (cytosol) and PsbA (thylakoids). The colocalization correlation coefficients calculated pairwise between organelles and autofluorescence were highly positive as opposed to the relatively low positive indices derived from labeled MCs. The lower correlation coefficients imply that only a portion of the labeled MC molecules were related spatially to the organelles in the cell.
Flat Wall Proximity Effect on Micro-Particle Sedimentation in Non-Newtonian Fluids
Authors: Farzam Rad Vahideh , Moradi Ali-Reza
Published: February 2020

We investigate the sedimentation of colloidal micro-spheres and red blood cells (RBCs) in non-Newtonian fluid - silicone oil with different viscosities. We use digital holographic microscopy (DHM) to obtain volumetric information of the sedimenting micro-objects. Especially, the numerical refocusing feature of DHM is used to extract the depth information of multiple particles moving inside the fluid. The effects of proximity to a flat wall and the non-Newtonian behavior on the sedimenting micro-spheres and RBCs are studied by trajectory analyzing and velocimetry. We observe that for lower viscosity values the proximity effect is more pronounced. The variation rate of the particle falling velocities versus their distance to the flat wall decreases by increasing the viscosity of the fluid. For RBCs, however, the decreasing of the velocity variations have a smoother trend. The experimental results verify the theoretical prediction that, similar to Newtonian case, a correction factor in Stokes’ law suffices for describing the wall effect.
Neutrophil extracellular trap-enriched supernatants carry microRNAs able to modulate TNF-α production by macrophages
Authors: Linhares-Lacerda Leandra , Temerozo Jairo Ramos , Ribeiro-Alves Marcelo , Azevedo Estefania P. , Mojoli Andres , Nascimento Michelle T. C. , Silva-Oliveira Gustavo , Savino Wilson , Foguel Debora , Bou-Habib Dumith Chequer , Saraiva Elvira M.
Published: February 2020

Neutrophil extracellular traps (NETs) emerge from the cell as a DNA scaffold associated with cytoplasmic and granular proteins, able to immobilize and kill pathogens. This association occurs following nuclear and granular membrane disintegration, allowing contact with the decondensed chromatin. Thus, it is reasonable to speculate that the DNA can also mix with miRNAs and carry them in NETs. Here, we report for the first time the presence of the miRNA carriers associated with NETs and miRNAs present in NET-enriched supernatants (NET-miRs), thus adding a novel class of molecules and new proteins that can be released and transported in the NET platform. We observed that the majority of NET-miRs were common to all four stimuli used (PMA, interleukin-8, amyloid fibrils andLeishmania), and that miRNA-142-3p carried by NETs down-modulates protein kinase Cα and regulates TNF-α production in macrophages upon NET interaction with these cells. Our findings unveil a novel role for NETs in the cell communication processes, allowing the conveyance of miRNA from neutrophils to neighboring cells.
Similar genomic patterns of clinical infective endocarditis and oral isolates of Streptococcus sanguinis and Streptococcus gordonii
Authors: Iversen Katrine Højholt , Rasmussen Louise Hesselbjerg , Al-Nakeeb Kosai , Armenteros Jose Juan Almagro , Jensen Christian Salgård , Dargis Rimtas , Lukjancenko Oksana , Justesen Ulrik Stenz , Moser Claus , Rosenvinge Flemming S. , Nielsen Xiaohui Chen , Christensen Jens Jørgen , Rasmussen Simon
Published: February 2020

Streptococcus gordonii and Streptococcus sanguinis belong to the Mitis group streptococci, which mostly are commensals in the human oral cavity. Though they are oral commensals, they can escape their niche and cause infective endocarditis, a severe infection with high mortality. Several virulence factors important for the development of infective endocarditis have been described in these two species. However, the background for how the commensal bacteria, in some cases, become pathogenic is still not known. To gain a greater understanding of the mechanisms of the pathogenic potential, we performed a comparative analysis of 38 blood culture strains, S. sanguinis (n = 20) and S. gordonii (n = 18) from patients with verified infective endocarditis, along with 21 publicly available oral isolates from healthy individuals, S. sanguinis (n = 12) and S. gordonii (n = 9). Using whole genome sequencing data of the 59 streptococci genomes, functional profiles were constructed, using protein domain predictions based on the translated genes. These functional profiles were used for clustering, phylogenetics and machine learning. A clear separation could be made between the two species. No clear differences between oral isolates and clinical infective endocarditis isolates were found in any of the 675 translated core-genes. Additionally, random forest-based machine learning and clustering of the pan-genome data as well as amino acid variations in the core-genome could not separate the clinical and oral isolates. A total of 151 different virulence genes was identified in the 59 genomes. Among these homologs of genes important for adhesion and evasion of the immune system were found in all of the strains. Based on the functional profiles and virulence gene content of the genomes, we believe that all analysed strains had the ability to become pathogenic.
The effects of a multispecies synbiotic on microbiome-related side effects of long-term proton pump inhibitor use: A pilot study
Authors: Horvath Angela , Leber Bettina , Feldbacher Nicole , Steinwender Markus , Komarova Irina , Rainer Florian , Blesl Andreas , Stadlbauer Vanessa
Published: February 2020

Side effects of proton pump inhibitors (PPI) can be linked to the changes in the intestinal microbiome that occur during therapy, especially in long-term users. Therefore, the microbiome might also be a key player in the reduction of PPI side effects. We tested the effects of a three-month intervention with a multispecies synbiotic on intestinal inflammation, gut barrier function, microbiome composition, routine laboratory parameters and quality of life in patients with long-term PPI therapy. Thirty-six patients received a daily dose of a multispecies synbiotic for three months and were clinically observed without intervention for another three months. After intervention 17% of patients reached normal calprotectin levels; the overall reduction did not reach statistical significance (−18.8 ng/mg; 95%CI: −50.5; 12.9, p = 0.2). Elevated zonulin levels could be significantly reduced (−46.3 ng/mg; 95%CI: −71.4; −21.2; p < 0.001). The abundance of Stomatobaculum in the microbiome was reduced and Bacillus increased during the intervention. Furthermore, albumin, alkaline phosphatase and thrombocyte count were significantly increased and aspartate transaminase was significantly decreased during intervention. Gastrointestinal quality of life showed significant improvements. In conclusion, microbiome-related side effects of long-term PPI use can be substantially reduced by synbiotic intervention. Further studies are warranted to optimize dosage and duration of the intervention.
Publisher Correction: A compact LED-based projection microstereolithography for producing 3D microstructures
Authors: Behroodi Ebrahim , Latifi Hamid , Najafi Farhood
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Generation of Schubert polynomial series via nanometre-scale photoisomerization in photochromic single crystal and double-probe optical near-field measurements
Authors: Uchiyama Kazuharu , Suzui Hirotsugu , Nakagomi Ryo , Saigo Hayato , Uchida Kingo , Naruse Makoto , Hori Hirokazu
Published: February 2020

Generation of irregular time series based on physical processes is indispensable in computing and artificial intelligence. In this report, we propose and demonstrate the generation of Schubert polynomials, which are the foundation of versatile permutations in mathematics, via optical near-field processes introduced in a photochromic crystal of diarylethene combined with a simple photon detection protocol. Optical near-field excitation on the surface of a photochromic single crystal yields a chain of local photoisomerization, forming a complex pattern on the opposite side of the crystal. The incoming photon travels through the nanostructured photochromic crystal, and the exit position of the photon exhibits a versatile pattern. We emulated trains of photons based on the optical pattern experimentally observed through double-probe optical near-field microscopy, where the detection position was determined based on a simple protocol, leading to Schubert matrices corresponding to Schubert polynomials. The versatility and correlations of the generated Schubert matrices could be reconfigured in either a soft or hard manner by adjusting the photon detection sensitivity. This is the first study of Schubert polynomial generation via physical processes or nanophotonics, paving the way for future nano-scale intelligence devices and systems.
Breast Arterial Calcification is Associated with the Progression of Coronary Atherosclerosis in Asymptomatic Women: A Preliminary Retrospective Cohort Study
Authors: Yoon Yeonyee Elizabeth , Kim Kyoung Min , Lee Wonjae , Han Jong Soo , Chun Eun Ju , Ahn Soyeon , Choi Sang Il , Yun Bo La , Suh Jung-Won
Published: February 2020

We evaluated whether breast arterial calcification (BAC) is associated with the progression of coronary atherosclerosis in asymptomatic women. This retrospective observational cohort study analysed asymptomatic women from the BBC registry. In 126 consecutive women (age, 54.5 ± 7.0 years) who underwent BAC evaluation and repeated coronary computed tomography angiography (CCTA) examinations, the coronary arterial calcification score (CACS) and segment stenosis score (SSS) were evaluated to assess the progression of coronary arterial calcification (CAC) and coronary atherosclerotic plaque (CAP). CAC and CAP progression were observed in 42 (33.3%) and 26 (20.6%) women, respectively (median interscan time, 4.3 years), and were associated with the presence of BAC and a higher BAC score at baseline. Women with BAC demonstrated higher CAC and CAP progression rates and showed higher chances for CAC and CAP progression during follow-up (p < 0.001 for both). In multivariable analyses, the BAC score remained independently associated with both CAC and CAP progression rates after adjustment for clinical risk factors (β = 0.087, p = 0.029; and β = 0.020, p = 0.010, respectively) and with additional adjustment for baseline CACS (β = 0.080, p = 0.040; and β = 0.019, p = 0.012, respectively) or SSS (β = 0.079, p = 0.034; and β = 0.019, p = 0.011, respectively). Thus, BAC may be related to the progression of coronary atherosclerosis and its evaluation may facilitate decision-making.
Associations of unhealthy lifestyles with metabolic syndrome in Chinese rural aged females
Authors: Wang Yuming , Tu Runqi , Yuan Huijuan , Shen Lijun , Hou Jian , Liu Xiaotian , Niu Miaomiao , Zhai Zhihan , Pan Mingming , Wang Chongjian
Published: February 2020

The purpose of this study is to update the prevalence of metabolic syndrome (MetS) and explore to identify the susceptible populations. A total of 38208 subjects aged 18 to 79 years were obtained from the Henan Rural Cohort Study (n = 39259). Five criteria (ATP β, IDF, JIS, CDS, EGIR) were used to estimate the prevalence of MetS. Multivariate logistic regression analysis was used to assess odds ratios (ORs) and 95% confidence interval (CI) of potential risk factors with MetS. The age-standardized prevalence of MetS were 27.87%, 24.63%, 27.40%, 18.00% and 8.91% according to the standard of ATP β, IDF, JIS, CDS, and EGIR, respectively. After adjusted for the potential confounding factors, aging, females, physical activity and the state of drinking were independent risk factors of MetS. MetS is positively associated with stroke and coronary heart disease in all five criteria (P < 0.01). The current data identify a high prevalence of MetS among Chinese rural adults. Especially for aged females with unhealthy lifestyle had a higher risk for MetS.
Analyses of crystal growth, optical, electrical, thermal and mechanical properties of an excellent detector-grade Cd0.9Mn0.1Te: V crystal
Authors: Luan Lijun , Gao Li , Lv Haohao , Yu Pengfei , Wang Tao , He Yi , Zheng Dan
Published: February 2020

A high-quality cadmium manganese tellurium (Cd0.9Mn0.1Te: V or VCMT) crystal was successfully grown via modified Te solution vertical Bridgman method with vanadium doping. The crystal structure and quality were evaluated by powder X-ray diffraction analysis. An infrared transmission spectroscope measured the transmittance of the crystal at 64%, which would suggest that the grown crystal possessed high purity and crystallinity. Ultraviolet-visible-near-infrared spectroscopy analysis obtained the forbidden band width of approximately 1.577 eV. The current-voltage test indicated that the VCMT crystal had a high resistivity of 2.07 × 1010 Ω·cm. Mechanical properties were measured by a Vickers microhardness tester. Crack surface morphology around the indentation was recorded. Furthermore, mechanical properties, such as microhardness, fracture toughness, brittleness index and yield strength were investigated and discussed. The thermal stability of the VCMT single crystal was determined by thermogravimetric analysis. A VCMT detector was fabricated with planar configuration structure, which showed a resolution of 11.62% of the 241Am at 59.5 keV peak.
An ultrasound-based referential of body height-adjusted normal liver organometry in school children from Bokito in rural Cameroon
Authors: Kamdem Severin Donald , Kuemkon Erve Martial , Kamguia Leonel Meyo , Tchanana Gladys K. , Konhawa Francis , Nche Frungwa , Oumarou Alim , Hamza Mamadou , Essomba René Ghislain , Kengne Michel , Ondigui Bienvenu Etogo , Assoumou Marie Claire Okomo , Brombacher Frank , Nono Justin Komguep
Published: February 2020

The grading system for ultrasonographic assessment of Schistosoma mansoni morbidity is crucial for evaluation of control programs. This requires prior definition of normal liver organometric ranges in the population from the endemic area. A cross-sectional study was conducted in a S. mansoni endemic area in rural Cameroon. 1002 Participants were screened and 234 of them, free from all common liver-affecting diseases in the area (schistosomiasis, malaria, hepatitis B and C) and with no ultrasonographic signs of liver disease were selected and their liver parameters measured by ultrasonography. All statistics were considered significant for p-values < 0.05. Normal dimensions of livers lobe sizes, portal vein wall thickness and portal vein diameters are reported. The liver organometric data are presented for the entire study population as a whole and separately for males and females as prediction plots, with observed values and fitted regression line with 95% confidence. Reference ranges for liver parameters (size, portal vein thickness and diameter) adjusted for body height established in the current study are novel for Cameroon. The prediction plots generated should improve the accuracy of the assessment of liver morbidity by ultrasonography in the region.
Circadian and Genetic Modulation of Visually-Guided Navigation in Drosophila Larvae
Authors: Asirim Ece Z. , Humberg Tim-Henning , Maier G. Larisa , Sprecher Simon G.
Published: February 2020

Organisms possess an endogenous molecular clock which enables them to adapt to environmental rhythms and to synchronize their metabolism and behavior accordingly. Circadian rhythms govern daily oscillations in numerous physiological processes, and the underlying molecular components have been extensively described from fruit flies to mammals. Drosophila larvae have relatively simple nervous system compared to their adult counterparts, yet they both share a homologous molecular clock with mammals, governed by interlocking transcriptional feedback loops with highly conserved constituents. Larvae exhibit a robust light avoidance behavior, presumably enabling them to avoid predators and desiccation, and DNA-damage by exposure to ultraviolet light, hence are crucial for survival. Circadian rhythm has been shown to alter light-dark preference, however it remains unclear how distinct behavioral strategies are modulated by circadian time. To address this question, we investigate the larval visual navigation at different time-points of the day employing a computer-based tracking system, which allows detailed evaluation of distinct navigation strategies. Our results show that due to circadian modulation specific to light information processing, larvae avoid light most efficiently at dawn, and a functioning clock mechanism at both molecular and neuro-signaling level is necessary to conduct this modulation.
VEGF and bFGF induction by nitric oxide is associated with hyperbaric oxygen-induced angiogenesis and muscle regeneration
Authors: Yamamoto Naoki , Oyaizu Takuya , Enomoto Mitsuhiro , Horie Masaki , Yuasa Masato , Okawa Atsushi , Yagishita Kazuyoshi
Published: February 2020

Hyperbaric oxygen (HBO) treatment promotes early recovery from muscle injury. Reactive oxygen species (ROS) upregulation is a key mechanism of HBO, which produces high O2 content in tissues through increased dissolution of oxygen at high pressure. Nitric oxide (NO), a type of ROS, generally stabilizes hypoxia-inducible factor (HIF) 1α and stimulates secretion of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) from endothelial cells and macrophages, which then induces angiogenesis. The purpose of the present study was to investigate whether HBO could promote angiogenesis via induction of NO and induce muscle regeneration in contused rat skeletal muscles. The HBO protocol consisted of 2.5 atmospheres absolute (ATA) 100% oxygen for 120 minutes, once a day for 5 consecutive days. We also evaluated the effects of a ROS inhibitor (NAC) or NOS-specific inhibitor (L-NAME) on HBO. HBO significantly increased NO3−, VEGF, and bFGF levels and stabilized HIF1α within 1 day. HBO promoted blood vessel formation at 3–7 days and muscle healing at 5–7 days after contusion. Administration of both NAC and L-NAME before HBO suppressed angiogenesis and muscle regeneration even after HBO. HBO thus promoted angiogenesis and muscle regeneration mainly through generation of NO in the early phase after muscle contusion injury.
A Long-Term Pilot Study on Sex and Spinal Cord Injury Shows Sexual Dimorphism in Functional Recovery and Cardio-Metabolic Responses
Authors: Ghnenis Adel B. , Burns Daniel T. , Osimanjiang Wupu , He Guanglong , Bushman Jared S.
Published: February 2020

More than a quarter of a million individuals in the US live with spinal cord injury (SCI). SCI disrupts neural circuitry to vital organs in the body. Despite severe incidences of long-term peripheral complications from SCI, the cardio-metabolic consequences and divergences in sex-related responses are not well described. We examined the effects of SCI on functional recovery, cardiac structure and function, body composition, and glucose metabolism on adult female and male Sprague Dawley (SD) rats. SCI was induced at T10 via contusion. Measured outcomes include behavioral assessment, body weight, dual-energy X-ray absorptiometry (DEXA) for body composition, echocardiography for cardiac structure and function, intraperitoneal glucose tolerance test (IPGTT) for glucose metabolism, insulin tolerance test (ITT), and histology of cardiac structure at the endpoint. There was a decrease in body fat percentage in both sexes, with SCI females disproportionately affected in percent body fat change. Left ventricular internal diameter during systole (LVIDs) was decreased in SCI females more than in SCI males. No significant differences in glucose metabolism were observed up to 20 weeks post-injury (PI). These data show significant cardio-metabolic differences as a consequence of SCI and, furthermore, that sex is an underlying factor in these differences.
Outdoor open pond batch production of green microalga Botryococcus braunii for high hydrocarbon production: enhanced production with salinity
Authors: Ruangsomboon Suneerat , Dimak Jantra , Jongput Buppha , Wiwatanaratanabutr Itsanun , Kanyawongha Pornthiwa
Published: February 2020

The aim of this work was to enhance the biodiesel quality and hydrocarbon content of green microalgaB.brauniistrain KMITL 2 cultivated outdoor under several salinity conditions in a batch production. The enhancement would be such that the microalgal biodiesel qualities met or exceeded the current standard so that it would be a good raw material for biodiesel production. The microalga production was in 300 L open oval ponds, among various salinity levels tested (0–20 ppt), 5 ppt was the best for hydrocarbon production, yielding 54.2 ± 0.9% hydrocarbon content and 5.1 ± 0.4 g L−1biomass. As the microalga production was scaled up by cultivation in 3,675 L open raceway pond under the 5 ppt condition, the microalga yielded a bit higher hydrocarbon content (58.8 ± 2.9%) but much lower biomass (2.5 ± 0.5 g L−1). The production in both oval and raceway ponds yielded a nearly identical biodiesel property (61.06–67.42 cetane number) which exceeded the value specified in international standards. Therefore, it was concluded thatB.brauniistrain KMITL 2 can be batch cultivated in an open pond at optimum salinity to yield sufficient hydrocarbon and biomass for biodiesel production.
Influence of the human papillomavirus on the radio-responsiveness of cancer stem cells in head and neck cancers
Authors: Reid Paul , Staudacher Alexander H. , Marcu Loredana G. , Olver Ian , Moghaddasi Leyla , Brown Michael P. , Bezak Eva
Published: February 2020

A growing proportion of head and neck cancers (HNC) result from HPV infection. Between HNC aetiological groups (HPV positive and HPV negative) clinical evidence demonstrates significantly better treatment response among HPV positive cancers. Cancer stem cells (CSCs) are identified in HNC tumour populations as agents of treatment resistance and a target for tumour control. This study examines dynamic responses in populations of a CSC phenotype in HNC cell lines following X-irradiation at therapeutic levels, and comparing between HPV statuses. Variations in CSC density between HPV groups showed no correlation with better clinical outcomes seen in the HPV positive status. CSC populations in HPV positive cell lines ranged from 1.9 to 4.8%, and 2.6 to 9.9% for HPV negative. Following 4 Gy X- irradiation however, HPV negative cell lines demonstrated more frequent and significantly greater escalation in CSC proportions, being 3-fold that of the HPV positive group at 72 hours post irradiation. CSC proportions of tumour populations are not fixed but subject to change in response to radiation at therapeutic dose levels. These findings imply a potential effect of aetiology on radio-responsiveness in CSCs, illustrating that clonogen treatment response may be more informative of therapy outcomes than inherent population density alone.
Spheroscope: A custom-made miniaturized microscope for tracking tumour spheroids in microfluidic devices
Authors: Rodríguez-Pena A. , Uranga-Solchaga J. , Ortiz-de-Solórzano C. , Cortés-Domínguez I.
Published: February 2020

3D cell culture models consisting of self-assembled tumour cells in suspension, commonly known as tumour spheroids, are becoming mainstream for high-throughput anticancer drug screening. A usual measurable outcome of screening studies is the growth rate of the spheroids in response to treatment. This is commonly quantified on images obtained using complex, expensive, optical microscopy systems, equipped with high-quality optics and customized electronics. Here we present a novel, portable, miniaturized microscope made of low-cost, mass-producible parts, which produces both fluorescence and phase-gradient contrast images. Since phase-gradient contrast imaging is based on oblique illumination, epi-illumination is used for both modalities, thus simplifying the design of the system. We describe the system, characterize its performance on synthetic samples and show proof-of-principle applications of the system consisting in imaging and monitoring the formation and growth of lung and pancreas cancer tumour spheroids within custom made microfluidic devices.
Genome-wide and expression pattern analysis of JAZ family involved in stress responses and postharvest processing treatments in Camellia sinensis
Authors: Zheng Yucheng , Chen Xuejin , Wang Pengjie , Sun Yun , Yue Chuan , Ye Naixing
Published: February 2020

The JASMONATE-ZIM DOMAIN (JAZ) family genes are key repressors in the jasmonic acid signal transduction pathway. Recently, the JAZ gene family has been systematically characterized in many plants. However, this gene family has not been explored in the tea plant. In this study, 13 CsJAZ genes were identified in the tea plant genome. Phylogenetic analysis showed that the JAZ proteins from tea and other plants clustered into 11 sub-groups. The CsJAZ gene transcriptional regulatory network predictive and expression pattern analyses suggest that these genes play vital roles in abiotic stress responses, phytohormone crosstalk and growth and development of the tea plant. In addition, the CsJAZ gene expression profiles were associated with tea postharvest processing. Our work provides a comprehensive understanding of the CsJAZ family and will help elucidate their contributions to tea quality during tea postharvest processing.
Hetero-integration enables fast switching time-of-flight sensors for light detection and ranging
Authors: Park Minseong , Baek Yongmin , Dinare Mesgana , Lee Doeon , Park Kyung-Ho , Ahn Jungho , Kim Dahee , Medina Joseff , Choi Won-Jin , Kim Sihwan , Zhou Changjie , Heo Junseok , Lee Kyusang
Published: February 2020

The time-of-flight (ToF) principle is a method used to measure distance and construct three-dimensional (3D) images by detecting the time or the phase difference between emitted and back-reflected optical flux. The ToF principle has been employed for various applications including light ranging and detection (LiDAR), machine vision and biomedical engineering; however, bulky system size and slow switching speed have hindered the widespread application of ToF technology. To alleviate these issues, a demonstration of hetero-integration of GaN-based high electron mobility transistors (HEMTs) and GaAs-based vertical cavity surface emitting lasers (VCSELs) on a single platform via a cold-welding method was performed. The hetero-integrated ToF sensors show superior switching performance when compared to silicon-transistor-based systems, miniaturizing size and exhibiting stable ranging and high-resolution depth-imaging. This hetero-integrated system of dissimilar material-based high-performance devices suggests a new pathway towards enabling high-resolution 3D imaging and inspires broader range application of heterogeneously integrated electronics and optoelectronics.
Evoked and spontaneous pain assessment during tooth pulp injury
Authors: Rossi Heather Lynn , See Lily Pachanin , Foster William , Pitake Saumitra , Gibbs Jennifer , Schmidt Brian , Mitchell Claire H. , Abdus-Saboor Ishmail
Published: February 2020

Injury of the tooth pulp is excruciatingly painful and yet the receptors and neural circuit mechanisms that transmit this form of pain remain poorly defined in both the clinic and preclinical rodent models. Easily quantifiable behavioral assessment in the mouse orofacial area remains a major bottleneck in uncovering molecular mechanisms that govern inflammatory pain in the tooth. In this study we sought to address this problem using the Mouse Grimace Scale and a novel approach to the application of mechanical Von Frey hair stimuli. We use a dental pulp injury model that exposes the pulp to the outside environment, a procedure we have previously shown produces inflammation. Using RNAscope technology, we demonstrate an upregulation of genes that contribute to the pain state in the trigeminal ganglia of injured mice. We found that mice with dental pulp injury have greater Mouse Grimace Scores than sham within 24 hours of injury, suggestive of spontaneous pain. We developed a scoring system of mouse refusal to determine thresholds for mechanical stimulation of the face with Von Frey filaments. This method revealed that mice with a unilateral dental injury develop bilateral mechanical allodynia that is delayed relative to the onset of spontaneous pain. This work demonstrates that tooth pain can be quantified in freely behaving mice using approaches common for other types of pain assessment. Harnessing these assays in the orofacial area during gene manipulation should assist in uncovering mechanisms for tooth pulp inflammatory pain and other forms of trigeminal pain.