bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification and Molecular Characterization of Superoxide Dismutases Isolated From A Scuticociliate Parasite: Physiological Role in Oxidative Stress
Authors: Folgueira Iria , Lamas Jesús , de Felipe Ana Paula , Sueiro Rosa Ana , Leiro José Manuel
Published: September 2019

Philasterides dicentrarchi is a free-living microaerophilic scuticociliate that can become a facultative parasite and cause a serious parasitic disease in farmed fish. Both the free-living and parasitic forms of this scuticociliate are exposed to oxidative stress associated with environmental factors and the host immune system. The reactive oxygen species (ROS) generated by the host are neutralized by the ciliate by means of antioxidant defences. In this study we aimed to identify metalloenzymes with superoxide dismutase (SOD) activity capable of inactivating the superoxide anion (•O2−) generated during induction of oxidative stress. P. dicentrarchi possesses the three characteristic types of SOD isoenzymes in eukaryotes: copper/zinc-SOD, manganese-SOD and iron-SOD. The Cu/Zn-SOD isoenzymes comprise three types of homodimeric proteins (CSD1-3) of molecular weight (MW) 34–44 kDa and with very different AA sequences. All Cu/Zn-SODs are sensitive to NaCN, located in the cytosol and in the alveolar sacs, and one of them (CSD2) is extracellular. Mn- and Fe-SOD transcripts encode homodimeric proteins (MSD and FSD, respectively) in their native state: a) MSD (MW 50 kDa) is insensitive to H2O2 and NaN3 and is located in the mitochondria; and b) FSD (MW 60 kDa) is sensitive to H2O2, NaN3 and the polyphenol trans-resveratrol and is located extracellularly. Expression of SOD isoenzymes increases when •O2− is induced by ultraviolet (UV) irradiation, and the increase is proportional to the dose of energy applied, indicating that these enzymes are actively involved in cellular protection against oxidative stress.
Genome-wide identification of and functional insights into the late embryogenesis abundant (LEA) gene family in bread wheat (Triticum aestivum)
Authors: Liu Hao , Xing Mingyan , Yang Wenbo , Mu Xiaoqian , Wang Xin , Lu Feng , Wang Yao , Zhang Linsheng
Published: September 2019

Late embryogenesis abundant (LEA) proteins are involved in the responses and adaptation of plants to various abiotic stresses, including dehydration, salinity, high temperature, and cold. Here, we report the first comprehensive survey of the LEA gene family in “Chinese Spring” wheat (Triticum aestivum). A total of 179TaLEAgenes were identified inT.aestivumand classified into eight groups. AllTaLEAgenes harbored the LEA conserved motif and had few introns.TaLEAgenes belonging to the same group exhibited similar gene structures and chromosomal locations. Our results revealed that mostTaLEAgenes contained abscisic acid (ABA)-responsive elements (ABREs) and variouscis-acting elements associated with the stress response in the promoter region and were induced under ABA and abiotic stress treatments. In addition, 8 genes representing each group were introduced intoE.coliand yeast to investigate the protective function of TaLEAs under heat and salt stress. TaLEAs enhanced the tolerance ofE.coliand yeast to salt and heat, indicating that these proteins have protective functions in host cells under stress conditions. These results increase our understanding of LEA genes and provide robust candidate genes for future functional investigations aimed at improving the stress tolerance of wheat.
Hydrogel-Based Organic Subdural Electrode with High Conformability to Brain Surface
Authors: Oribe Shuntaro , Yoshida Shotaro , Kusama Shinya , Osawa Shin-ichiro , Nakagawa Atsuhiro , Iwasaki Masaki , Tominaga Teiji , Nishizawa Matsuhiko
Published: September 2019

A totally soft organic subdural electrode has been developed by embedding an array of poly(3,4-ethylenedioxythiophene)-modified carbon fabric (PEDOT-CF) into the polyvinyl alcohol (PVA) hydrogel substrate. The mesh structure of the stretchable PEDOT-CF allowed stable structural integration with the PVA substrate. The electrode performance for monitoring electrocorticography (ECoG) was evaluated in saline solution, on ex vivo brains, and in vivo animal experiments using rats and porcines. It was demonstrated that the large double-layer capacitance of the PEDOT-CF brings low impedance at the frequency of brain wave including epileptic seizures, and PVA hydrogel substrate minimized the contact impedance on the brain. The most important unique feature of the hydrogel-based ECoG electrode was its shape conformability to enable tight adhesion even to curved, grooved surface of brains by just being placed. In addition, since the hydrogel-based electrode is totally organic, the simultaneous ECoG-fMRI measurements could be conducted without image artifacts, avoiding problems induced by conventional metallic electrodes.
An anticancer Os(II) bathophenanthroline complex as a human breast cancer stem cell-selective, mammosphere potent agent that kills cells by necroptosis
Authors: Novohradsky Vojtech , Markova Lenka , Kostrhunova Hana , Trávníček Zdeněk , Brabec Viktor , Kasparkova Jana
Published: September 2019

Conventional chemotherapy is mostly effective in the treatment of rapidly-dividing differentiated tumor cells but has limited application toward eliminating cancer stem cell (CSC) population. The presence of a very small number of CSCs may contribute to the development of therapeutic resistance, metastases, and relapse. Thus, treatment failure by developing novel anticancer drugs capable of effective targeting of CSCs is at present a major challenge for research focused on chemotherapy of cancer. Here, we show that Os(II) complex 2 [Os(η6-pcym)(bphen)(dca)]PF6 (pcym = p-cymene, bphen = bathophenanthroline, and dca = dichloroacetate), is capable of efficient and selective killing CSCs in heterogeneous populations of human breast cancer cells MCF-7 and SKBR-3. Notably, its remarkable submicromolar potency to kill CSCs is considerably higher than that of its Ru analog, [Ru(η6-pcym)(bphen)(dca)]PF6 (complex 1) and salinomycin, one of the most selective CSC-targeting compounds hitherto identified. Furthermore, Os(II) complex 2 reduces the formation, size, and viability of three-dimensional mammospheres which more closely reflect the tumor microenvironment than cells in traditional two-dimensional cultures. The antiproliferation studies and propidium iodide staining using flow cytometry suggest that Os(II) complex 2 induces human breast cancer stem cell death predominantly by necroptosis, a programmed form of necrosis. The results of this study demonstrate the promise of Os(II) complex 2 in treating human breast tumors. They also represent the foundation for further preclinical and clinical studies and applications of Os(II) complex 2 to comply with the emergent need for human breast CSCs-specific chemotherapeutics capable to treat chemotherapy-resistant and relapsed human breast tumors.
Energy-efficiency of Cardiomyocyte Stimulation with Rectangular Pulses
Authors: Laasmaa Martin , Lu Pengfei , Veletić Mladen , Louch William E. , Bergsland Jacob , Balasingham Ilangko , Vendelin Marko
Published: September 2019

In cardiac pacemaker design, energy expenditure is an important issue. This work aims to explore whether varying stimulation pulse configuration is a viable optimization strategy for reducing energy consumption by the pacemaker. A single cardiomyocyte was used as an experimental model. Each cardiomyocyte was stimulated with different stimulation protocols using rectangular waveforms applied in varying number, in short succession. The amplitude, the width of each pulse, and the interval between consecutive pulses were modified. The application of multiple pulses in a short sequence led to a reduction of the threshold voltage required for stimulation when compared to a single pulse. However, none of the employed multi-pulse sequences reduced the overall energy expenditure of cell stimulation when compared to a single pulse stimulation. Among multiple pulse protocols, a combination of two short pulses (1 ms) separated with a short interval (0.5 ms) had the same energy requirements as a single short pulse (1 ms), but required the application of significantly less voltage. While increasing the number of consecutive pulses does not reduce the energy requirements of the pacemaker, the reduction in threshold voltage can be considered in practice if lower stimulation voltages are desired.
Prognostic Significance of Left Ventricular Fibrosis Assessed by T1 Mapping in Patients with Atrial Fibrillation and Heart Failure
Authors: Zhao Lei , Li Songnan , Ma Xiaohai , Bai Rong , Liu Nian , Li Ning , Schoenhagen Paul , Ma Changsheng
Published: September 2019

This study sought to investigate whether left ventricular (LV) fibrosis quantified by T1 mapping can be used as a biomarker to predict outcome in patients with atrial fibrillation (AF) and heart failure (HF). 108 patients with AF and HF were included in this study. They underwent cardiac magnetic resonance, including T1 mapping sequence to assess LV fibrosis between May 2014 to May 2016. Patients received catheter ablation for AF and pharmacological treatment for HF. The primary endpoint was a composite adverse outcome of cardiac death, subsequent HF or stroke, subsequent HF was the secondary endpoint. During follow up (median: 23 months, Q1-Q3: 11 to 28 months), 1 cardiac death, 12 strokes, and 42 HF episodes occurred. LV extracellular volume fraction (ECV) was predictive of composite adverse outcome and subsequent HF (all p < 0.001). In multivariable analysis, LV ECV was an independent predictor of composite adverse outcome (hazard ratio (HR): 1.258, 95% confidence interval (CI): 1.140–1.388, p < 0.001) and subsequent HF (HR: 1.223, 95% CI: 1.098–1.363, p < 0.001). LV fibrosis measured by T1 mapping indices significantly predicts composite adverse outcomes and subsequent HF in patients with AF and HF.
Lethal Effect of Total Dissolved Gas-Supersaturated Water with Suspended Sediment on River Sturgeon (Acipenser dabryanus)
Authors: Liu Xiaoqing , Li Na , Feng Cuixia , Fu Chenghua , Gong Quan , Lai Jiansheng , Jiang Zhu , Yang Yao , Shi Haoran
Published: September 2019

High total dissolved gas (TDG) levels and excessive suspended sediment (SS) concentrations pose serious threats to fish survival during flood season. However, little information is available on the effects of TDG supersaturation with varying SS concentrations on fish. In this study, laboratory experiments were performed to investigate the effects of TDG supersaturation with varying SS concentrations on five-month-old river sturgeons (Acipenser dabryanus). The test fish were exposed to combinations of SS concentrations (0, 200, 600 and 1,000 mg/L) and TDG levels (125, 130, 135 and 140%), and their mortality and median lethal time (LT50) were quantified. The fish showed abnormal behaviors (e.g., quick breathing, fast swimming and an agitated escape response) and symptoms of gas bubble disease (GBD). SS increased the mortality of river sturgeon exposed to TDG supersaturation. Furthermore, the LT50 values at 125% TDG were 4.47, 3.11, 3.07 and 2.68 h for the different SS concentrations (0, 200, 600 and 1,000 mg/L, respectively), representing a significant decrease in LT50 with increasing SS. However, at higher TDG levels (130–140%), there was no significant increase in LT50 with increasing SS. Therefore, river sturgeon showed weak tolerance of TDG-supersaturated water with SS.
Overlapping protein-coding genes in human genome and their coincidental expression in tissues
Authors: Chen Chao-Hsin , Pan Chao-Yu , Lin Wen-chang
Published: September 2019

The completion of human genome sequences and the advancement of next-generation sequencing technologies have engendered a clear understanding of all human genes. Overlapping genes are usually observed in compact genomes, such as those of bacteria and viruses. Notably, overlapping protein-coding genes do exist in human genome sequences. Accordingly, we used the current Ensembl gene annotations to identify overlapping human protein-coding genes. We analysed 19,200 well-annotated protein-coding genes and determined that 4,951 protein-coding genes overlapped with their adjacent genes. Approximately a quarter of all human protein-coding genes were overlapping genes. We observed different clusters of overlapping protein-coding genes, ranging from two genes (paired overlapping genes) to 22 genes. We also divided the paired overlapping protein-coding gene groups into four subtypes. We found that the divergent overlapping gene subtype had a stronger expression association than did the subtypes of 5ʹ-tandem overlapping and 3ʹ-tandem overlapping genes. The majority of paired overlapping genes exhibited comparable coincidental tissue expression profiles; however, a few overlapping gene pairs displayed distinctive tissue expression association patterns. In summary, we have carefully examined the genomic features and distributions about human overlapping protein-coding genes and found coincidental expression in tissues for most overlapping protein-coding genes.
Effect of DPP-IV Inhibitors on Glycemic Variability in Patients with T2DM: A Systematic Review and Meta-Analysis
Authors: Lee Subin , Lee Heeyoung , Kim Yoonhye , Kim EunYoung
Published: September 2019

Glycemic variability (GV) has been an emerging target for preventing complications related to type 2 diabetes. For reducing GV, DPP-IV inhibitors have shown effectiveness compared to other oral anti-hyperglycemic drugs (OADs), but systematic evaluation has yet to be existed. A systematic review and meta-analysis of randomized controlled trials (RCTs) were performed to evaluate the effect of DPP-IV inhibitors compared with other OADs, on GV as measured by mean amplitude of glycemic excursions (MAGE). Searches were conducted using Pubmed, EMBASE, and the Cochrane Library, from which eligible studies were retrieved; seven RCTs were included in the analysis. DPP-IV inhibitors were found to significantly reduce MAGE compared to other OADs (mean difference = −14.61; 95% CI = −19.00 to −10.21; p < 0.0001) without significant heterogeneity among sulfonylureas (mean difference = −14.93; 95% CI = −21.60 to −8.26; p < 0.0001). Initial combination therapy with DPP-IV inhibitors more effectively reduced MAGE than stepwise add-on therapies (p = 0.006), although no differences in MAGE were found based on HbA1c values. These findings indicate that DPP-IV inhibitors are promising alternatives for reducing GV in type 2 diabetes patients. However, further studies utilizing larger numbers of patients and longer-term follow-ups are needed.
An increased cell cycle gene network determines MEK and Akt inhibitor double resistance in triple-negative breast cancer
Authors: van der Noord Vera E. , McLaughlin Ronan P. , Smid Marcel , Foekens John A. , Martens John W. M. , Zhang Yinghui , van de Water Bob
Published: September 2019

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with poor clinical prognosis and limited targeted treatment strategies. Kinase inhibitor screening of a panel of 20 TNBC cell lines uncovered three critical TNBC subgroups: 1) sensitive to only MEK inhibitors; 2) sensitive to only Akt inhibitors; 3) resistant to both MEK/Akt inhibitors. Using genomic, transcriptomic and proteomic datasets of these TNBC cell lines we unravelled molecular features associated with the MEK and Akt drug resistance. MEK inhibitor-resistant TNBC cell lines were discriminated from Akt inhibitor-resistant lines by the presence of PIK3CA/PIK3R1/PTEN mutations, high p-Akt and low p-MEK levels, yet these features could not distinguish double-resistant cells. Gene set enrichment analyses of transcriptomic and proteomic data of the MEK and Akt inhibitor response groups revealed a set of cell cycle-related genes associated with the double-resistant phenotype; these genes were overexpressed in a subset of breast cancer patients. CDK inhibitors targeting the cell cycle programme could overcome the Akt and MEK inhibitor double-resistance. In conclusion, we uncovered molecular features and alternative treatment strategies for TNBC that are double-resistant to Akt and MEK inhibitors.
Automatic choroidal segmentation in OCT images using supervised deep learning methods
Authors: Kugelman Jason , Alonso-Caneiro David , Read Scott A. , Hamwood Jared , Vincent Stephen J. , Chen Fred K. , Collins Michael J.
Published: September 2019

The analysis of the choroid in the eye is crucial for our understanding of a range of ocular diseases and physiological processes. Optical coherence tomography (OCT) imaging provides the ability to capture highly detailed cross-sectional images of the choroid yet only a very limited number of commercial OCT instruments provide methods for automatic segmentation of choroidal tissue. Manual annotation of the choroidal boundaries is often performed but this is impractical due to the lengthy time taken to analyse large volumes of images. Therefore, there is a pressing need for reliable and accurate methods to automatically segment choroidal tissue boundaries in OCT images. In this work, a variety of patch-based and fully-convolutional deep learning methods are proposed to accurately determine the location of the choroidal boundaries of interest. The effect of network architecture, patch-size and contrast enhancement methods was tested to better understand the optimal architecture and approach to maximize performance. The results are compared with manual boundary segmentation used as a ground-truth, as well as with a standard image analysis technique. Results of total retinal layer segmentation are also presented for comparison purposes. The findings presented here demonstrate the benefit of deep learning methods for segmentation of the chorio-retinal boundary analysis in OCT images.
An integrated genome-wide multi-omics analysis of gene expression dynamics in the preimplantation mouse embryo
Authors: Israel Steffen , Ernst Mathias , Psathaki Olympia E. , Drexler Hannes C. A. , Casser Ellen , Suzuki Yutaka , Makalowski Wojciech , Boiani Michele , Fuellen Georg , Taher Leila
Published: September 2019

Early mouse embryos have an atypical translational machinery that consists of cytoplasmic lattices and is poorly competent for translation. Hence, the impact of transcriptomic changes on the operational level of proteins is predicted to be relatively modest. To investigate this, we performed liquid chromatography–tandem mass spectrometry and mRNA sequencing at seven developmental stages, from the mature oocyte to the blastocyst, and independently validated our data by immunofluorescence and qPCR. We detected and quantified 6,550 proteins and 20,535 protein-coding transcripts. In contrast to the transcriptome – where changes occur early, mostly at the 2-cell stage – our data indicate that the most substantial changes in the proteome take place towards later stages, between the morula and blastocyst. We also found little to no concordance between the changes in protein and transcript levels, especially for early stages, but observed that the concordance increased towards the morula and blastocyst, as did the number of free ribosomes. These results are consistent with the cytoplasmic lattice-to-free ribosome transition being a key mediator of developmental regulation. Finally, we show how these data can be used to appraise the strengths and limitations of mRNA-based studies of pre-implantation development and expand on the list of known developmental markers.
Tonsillectomy does not reduce asthma in children: A longitudinal follow-up study using a national sample cohort
Authors: Kim So Young , Oh Dong Jun , Choi Hyo Geun
Published: September 2019

This study aimed to investigate the occurrence of tonsillectomy in asthmatic children using a control group with a comparable frequency of a preoperative history of asthma. Asthmatic children ≤15 years old were collected from the Korean Health Insurance Review and Assessment Service - National Sample Cohort (HIRA-NSC) from 2002 through 2013. In study I, asthmatic children who had undergone a tonsillectomy (n = 2,326) and control I participants (n = 9,304) were selected and matched 1:4 for age, sex, income, and region of residence but not a preoperative history of asthma. In study II, a preoperative history of asthma was additionally matched for between the tonsillectomy (n = 2,280) and the new control II participants (n = 9,120). The margin of equivalence of difference (control-tonsillectomy) for asthma was set at −0.05 to 0.05 per year. In addition, repeated measures ANOVA was performed for tonsillectomy according to yearly changes in asthma, status asthmaticus, and admission. In study I, the preoperative frequencies of asthma, status asthmaticus, and admission were higher in the tonsillectomy group than in the control group (P ≤ 0.001). The frequencies of postoperative asthma, status asthmaticus, and admission were lower in the tonsillectomy group than in the control I group for 3 years. In study II, the frequencies of postoperative 1-, 2-, and 3-year asthma and admission were not lower in the tonsillectomy group than in the control II group. Tonsillectomy did not further reduce the frequency of asthma in patients who underwent this procedure compared to the control group when a preoperative history of asthma history was equally matched between the two groups.
Direct comparison of target-reactivity and cross-reactivity induced by CAR- and BiTE-redirected T cells for the development of antibody-based T-cell therapy
Authors: Maruta Masaki , Ochi Toshiki , Tanimoto Kazushi , Asai Hiroaki , Saitou Takashi , Fujiwara Hiroshi , Imamura Takeshi , Takenaka Katsuto , Yasukawa Masaki
Published: September 2019

The development of chimeric antigen receptor (CAR) and bispecific T-cell engager (BiTE) has led to the successful application of cancer immunotherapy. The potential reactivity mediated by CAR- and BiTE-redirected T cells needs to be assessed to facilitate the application of these treatment options to a broader range of patients. Here, we have generated CAR and BiTE possessing the same single chain fragment variable (scFv) specific for the HLA-A2/NY-ESO-1157-165 complex (A2/NY-ESO-1157). Using HLA-A2+NY-ESO-1+ myeloma cells and peptides presented by HLA-A2 molecules as a model, both sets of redirected T cells recognized and killed HLA-A2+NY-ESO-1+ myeloma cells in an A2/NY-ESO-1157-specific manner in vitro. Moreover, CAR- and BiTE-activated T cells showed similar functional avidity, as assessed by cytokine production and killing activity, both displaying antitumor reactivity against HLA-A2+NY-ESO-1+ myeloma cells in vivo. Interestingly, cross-reactivity for homologous peptides presented by HLA-A*02:01 and NY-ESO-1157 peptide presented by HLA-A2 alleles was not identical between CAR- and BiTE-redirected T cells, probably due to structural differences of modified antibodies. These results have demonstrated that both antitumor CAR- and BiTE-activated T cells have comparable potential to recognize tumors, while paying attention to unknown off-target reactivity that would differ for each antibody-based modality even if the same scFv was employed.
Nuclease dead Cas9 is a programmable roadblock for DNA replication
Authors: Whinn Kelsey S. , Kaur Gurleen , Lewis Jacob S. , Schauer Grant D. , Mueller Stefan H. , Jergic Slobodan , Maynard Hamish , Gan Zhong Yan , Naganbabu Matharishwan , Bruchez Marcel P. , O’Donnell Michael E. , Dixon Nicholas E. , van Oijen Antoine M. , Ghodke Harshad
Published: September 2019

Limited experimental tools are available to study the consequences of collisions between DNA-bound molecular machines. Here, we repurpose a catalytically inactivated Cas9 (dCas9) construct as a generic, novel, targetable protein–DNA roadblock for studying mechanisms underlying enzymatic activities on DNA substrates in vitro. We illustrate the broad utility of this tool by demonstrating replication fork arrest by the specifically bound dCas9–guideRNA complex to arrest viral, bacterial and eukaryotic replication forks in vitro.
Pigeons integrate visual motion signals differently than humans
Authors: Hataji Yuya , Kuroshima Hika , Fujita Kazuo
Published: September 2019

Perceiving motion is a fundamental ability for animals. Primates integrate local 1D motion across orientation and space to compute a rigid 2D motion. It is unknown whether the rule of 2D motion integration is universal within the vertebrate clade; comparative studies of animals with different ecological backgrounds from primates may help answer that question. Here we investigated 2D motion integration in pigeons, using hierarchically structured motion stimuli, namely a barber-pole illusion and plaid motion. The pigeons were trained to report the direction of motion of random dots. When a barber-pole or plaid stimulus was presented, they reported the direction perpendicular to the grating orientation for barber-pole and the vector average of two component gratings for plaid motion. These results demonstrate that pigeons perceive different directions than humans from the same motion stimuli, and suggest that the 2D integrating rules in the primate brain has been elaborated through phylogenetic or ecological factors specific to the clade.
Vector compositions change across forested to deforested ecotones in emerging areas of zoonotic malaria transmission in Malaysia
Authors: Hawkes Frances M. , Manin Benny O. , Cooper Amanda , Daim Sylvia , R. Homathevi , Jelip Jenarun , Husin Tanrang , Chua Tock H.
Published: September 2019

In lowland areas of Malaysia, Plasmodium knowlesi infection is associated with land use change and high proportions of the vector Anopheles balabacensis. We conducted a 15-month study in two Malaysian villages to determine the effect of habitat on vector populations in understudied high-altitude, high-incidence districts. Anopheles mosquitoes were sampled in human settlements, plantations and forest edges, and screened for Plasmodium species by PCR. We report the first An. donaldi positive for P. knowlesi. This potential vector was associated with habitat fragmentation measured as disturbed forest edge:area ratio, while An. balabacensis was not, indicating fragmented land use could favour An. donaldi. Anopheline species richness and diversity decreased from forest edge, to plantation, to human settlement. Greater numbers of An. balabacensis and An. donaldi were found in forest edges compared to human settlements, suggesting exposure to vectors and associated zoonoses may be greater for people entering this habitat.
Behavioural responses of the hagfish Eptatretus stoutii to nutrient and noxious stimuli
Authors: Glover Chris N. , Newton Dustin , Bajwa Jasmin , Goss Greg G. , Hamilton Trevor J.
Published: September 2019

The suitability of a traditional testing paradigm (e.g. choice chamber) for assessing chemosensory behaviour in the Pacific hagfish, Eptatretus stoutii, was examined. Actively-swimming hagfish, tested at night, showed no preference for any region of a T-maze in the absence of a stimulus, but in the presence of an olfactory food cue, spent significantly more time in the zone where the cue was placed. Conversely, hagfish avoided spending time in the zone the fish anaesthetic 3-amino benzoic acid ethylester (MS-222) was placed, and demonstrated significantly more reversal responses in which the fish moved its body backwards. These data suggest that hagfish are an amenable model species for laboratory testing of behaviour.
CPT1A plays a key role in the development and treatment of multiple sclerosis and experimental autoimmune encephalomyelitis
Authors: Mørkholt Anne Skøttrup , Trabjerg Michael Sloth , Oklinski Michal Krystian Egelund , Bolther Luise , Kroese Lona John , Pritchard Colin Eliot Jason , Huijbers Ivo Johan , Nieland John Dirk Vestergaard
Published: September 2019

Human mutations in carnitine palmitoyl transferase 1A (CPT1A) are correlated with a remarkably low prevalence of multiple sclerosis (MS) in Inuits (P479L) and Hutterites (G710E). To elucidate the role of CPT1A, we established a Cpt1a P479L mouse strain and evaluated its sensitivity to experimental autoimmune encephalomyelitis (EAE) induction. Since CPT1a is a key molecule in lipid metabolism, we compared the effects of a high-fat diet (HFD) and normal diet (ND) on disease progression. The disease severity increased significantly in WT mice compared to that in Cpt1 P479L mice. In addition, WT mice receiving HFD showed markedly exacerbated disease course when compared either with Cpt1a P479L mice receiving HFD or WT control group receiving ND. Induction of EAE caused a significant decrease of myelin basic protein expression in the hindbrain of disease affected WT mice in comparison to Cpt1a P479L mice. Further, WT mice showed increased expression of oxidative stress markers like Nox2 and Ho-1, whereas expression of mitochondrial antioxidants regulator Pgc1α was increased in Cpt1a P479L mice. Our results suggest that, lipids metabolism play an important role in EAE, as shown by the higher severity of disease progression in both WT EAE and WT EAF HFD-fed mice in contrast to their counterpart Cpt1a P479L mutant mice. Interestingly, mice with downregulated lipid metabolism due to the Cpt1a P479L mutation showed resistance to EAE induction. These findings support a key role for CPT1A in the development of EAE and could be a promising target in MS treatment.
Semaphorin 6A Attenuates the Migration Capability of Lung Cancer Cells via the NRF2/HMOX1 Axis
Authors: Chen Li-Han , Liao Che-Yu , Lai Liang-Chuan , Tsai Mong-Hsun , Chuang Eric Y.
Published: September 2019

Cell migration is a fundamental feature of cancer recurrence. Since recurrence is correlated with high mortality in lung cancer, it follows that reducing cell migration would decrease recurrence and increase survival rates. Semaphorin-6A (SEMA6A), a protein initially known as a regulator of axonal guidance, is down-regulated in lung cancer tissue, and low levels of SEMA6A are associated with cancer recurrence. Thus, we hypothesized that SEMA6A could suppress cancer cell migration. In this study, we found that the migration capability of H1299 lung cancer cells decreased with SEMA6A overexpression, while it increased with SEMA6A silencing. Moreover, silencing of the cellular homeostasis protein Heme-oxygenase-1 (HMOX1) and/or the transcription factor Nuclear Factor, Erythroid-2-Like-2 (NRF2) reversed the migration-suppressing effect of SEMA6A and the SEMA6A-driven alterations in expression of urokinase insulin-like-growth-factor-binding-protein-3, Matrix metalloproteinase (MMP)-1, and MMP9, the downstream effectors of HMOX1. Taken together, these results demonstrate that SEMA6A is a potential suppressor of cancer migration that functions through the NRF2/HMOX1 axis. Our results explain why low SEMA6A is linked to high recurrence in the clinical setting and suggest that SEMA6A could be useful as a biomarker or target in lung cancer therapy.
Double-sided slippery liquid-infused porous materials using conformable mesh
Authors: Geraldi Nicasio R. , Guan Jian H. , Dodd Linzi E. , Maiello Pietro , Xu Ben B. , Wood David , Newton Michael I. , Wells Gary G. , McHale Glen
Published: September 2019

Often wetting is considered from the perspective of a single surface of a rigid substrate and its topographical properties such as roughness or texture. However, many substrates, such as membranes and meshes, have two useful surfaces. Such flexible substrates also offer the potential to be formed into structures with either a double-sided surface (e.g. by joining the ends of a mesh as a tape) or a single-sided surface (e.g. by ends with a half-twist). When a substrate possesses holes, it is also possible to consider how the spaces in the substrate may be connected or disconnected. This combination of flexibility, holes and connectedness can therefore be used to introduce topological concepts, which are distinct from simple topography. Here, we present a method to create a Slippery Liquid-Infused Porous Surface (SLIPS) coating on flexible conformable doubled-sided meshes and for coating complex geometries. By considering the flexibility and connectedness of a mesh with the surface properties of SLIPS, we show it is possible to create double-sided SLIPS materials with high droplet mobility and droplet control on both faces. We also exemplify the importance of flexibility using a mesh-based SLIPS pipe capable of withstanding laminar and turbulent flows for 180 and 90 minutes, respectively. Finally, we discuss how ideas of topology introduced by the SLIPS mesh might be extended to create completely new types of SLIPS systems, such as Mobius strips and auxetic metamaterials.
First-principles investigation on electronic properties and band alignment of group III monochalcogenides
Authors: Ren Chongdan , Wang Sake , Tian Hongyu , Luo Yi , Yu Jin , Xu Yujing , Sun Minglei
Published: September 2019

Using first-principles calculations, we investigated the electronic properties and band alignment of monolayered group III monochalcogenides. First, we calculated the structural and electronic properties of six group III monochalcogenides (GaS, GaSe, GaTe, InS, InSe, and InTe). We then investigated their band alignment and analysed the possibilities of forming type-I and type-II heterostructures by combining these compounds with recently developed two-dimensional (2D) semiconducting materials, as well as forming Schottky contacts by combining the compounds with 2D Dirac materials. We aim to provide solid theoretical support for the future application of group III monochalcogenides in nanoelectronics, photocatalysis, and photovoltaics.
Using wearable devices for assessing the impacts of hair exposome in Brazil
Authors: De Vecchi Rodrigo , da Silveira Carvalho Ripper Júlia , Roy Daniel , Breton Lionel , Germano Marciano Alexandre , Bernardo de Souza Plínio Marcos , de Paula Corrêa Marcelo
Published: September 2019

Previous studies have shown that physicochemical properties of hair can be impacted by internal and environmental exposures ranging from chemical stressors to weather. Besides the effects on hair, these exposures, termed “exposome”, can act on specific organs including skin, as a synergistic damaging effect of UV exposure and pollution on human surfaces. The combination of several environmental factors such as sun exposure, temperature, relative humidity, air pollution and photo-oxidation caused by ground level ozone impacts hair properties such as melanin oxidation, protein content, surface quality and structural components. Therefore, exposome studies can reveal new hypotheses on how epithelia and hair could be affected by daily life environment and routine. The aim of this study was to evaluate the impact of several environmental aggressors on human surfaces, using portable and wearable devices for monitoring exposome. To better understand the underlying mechanisms associated with environmental factors, two subjects wore multiple sensors to capture the meteorological conditions biking through urban areas in summer and winter. Temperature, humidity, UV radiation and ozone concentration were recorded and hair swatches of different types, including natural, bleached/colored, colored and gray, were exposed on the helmets. Silicon wristbands were used on skin to identify main chemical aggressors. After exposure, hair swatches were analyzed by surface microscopy analysis, oxidation markers and more than 1,500 chemicals were evaluated on the bracelets. Correlated with GPS and monitoring data, all these results provide insights on how environmental stressors affect the quality of different hair types and body surface according to exposure routine. Our results suggest extreme climate conditions associated with hair damage and photo-oxidative marker linked to the environmental aggressors. Polycyclic aromatic hydrocarbons (PAH) indicate possible causes of hair damages. This is the first meteorotropic study of its kind, combining environmental aggressors related to hair damage, opening new research hypothesis further studies on exposome.
Structural, Photophysical, and Electronic Properties of CH3NH3PbCl3 Single Crystals
Authors: Hsu Hao-Ping , Li Liang-Chen , Shellaiah Muthaiah , Sun Kien Wen
Published: September 2019

Methylammonium lead chloride (CH3NH3PbCl3 or MAPbCl3) single crystals were fabricated using the inverse temperature crystallization method, and their structural, photophysical, and electronic characteristics were studied using temperature dependent optical spectroscopy, X-ray diffraction (XRD), current-voltage, and Hall measurements. The changes in absorption and photoluminescence properties accompanied with structural changes in crystal lattice were studied within a broad temperature range of 300–20 K. XRD investigations reveal that phase changes took placed around 180 K and 175 K. At a temperature below 170 K, two different crystallographic phases were found to co-exist in the photoluminescence spectra. An asymmetric line shape with broad and weak shoulders near the absorption edges was observed in all of the major PL peaks. The weak shoulders are attributed to the missing chloride atoms on the crystal surface. The photoluminescence intensity of the crystals was strongly influenced by the environment, thereby indicating that the carrier recombination is affected by the physical desorption/absorption of gas molecules at the crystal surface. Moreover, vibronic replicas in the photoluminescence spectra at low temperature were observed for the first time. The origins of these replicas are attributed to the coupling between the vibrational/librational motions of the organic cations and the photoexcited electrons. Finally, the Hall and current-voltage measurements confirm that the crystal is an n-type semiconductor with a carrier concentration of ~2.63 × 1011 cm−3, a mobility of 4.14 cm2/V•s, and a conductivity of 1.8 × 10−8Ω−1 cm−1 under dark and room temperature conditions.
Differential effect of GLUT1 overexpression on survival and tumor immune microenvironment of human papilloma virus type 16-positive and -negative cervical cancer
Authors: Kim Byoung Hyuck , Chang Ji Hyun
Published: September 2019

Glucose transporter-1 (GLUT1) has been proposed as a prognosticator in various cancers associated with therapeutic resistance and immune evasion; however little data is available on the role of GLUT1 in cervical cancer. Most cervical cancers are caused by human papilloma virus (HPV), but studies on the treatment response and prognosis depending on the HPV subtype, are conflicting. This hypothesis-generating study aims to investigate the prognostic impact of GLUT1 in cervical cancer, in conjunction with HPV subtype. Clinicopathologic factors, along with mRNA expression data were obtained using The Cancer Genome Atlas database. Tumor HPV status and immune cell scores were extracted from previous publications. In total, 298 patients were analyzed. High GLUT1 expression was associated with old age, squamous cell carcinoma, high tumor stage, pelvic lymph node metastases, and low hysterectomy rate. Multivariate survival analysis revealed that high GLUT1 expression (Hazard ratio (HR) 2.57, p = 0.002) and HPV16 subtype (HR 0.56, p = 0.033) were independent prognostic factors for overall survival. In the subgroup analysis, poor prognostic impact of high GLUT1 expression was maintained in HPV16-positive group (p < 0.001), but not in HPV16-negative group (p = 0.495). Decreased immune cell scores of CD8+ T cells, B cells, and Th1 cells by high GLUT1 expression were observed only in HPV16-positive group. In conclusion, these results suggested that GLUT1 expression and HPV16 subtype might have an independent prognostic value in cervical cancer. GLUT1-mediated immunomodulation might be an important cause of treatment failure, especially in HPV16-positive group.
Improving the Function and Engraftment of Transplanted Pancreatic Islets Using Pulsed Focused Ultrasound Therapy
Authors: Razavi Mehdi , Zheng Fengyang , Telichko Arsenii , Wang Jing , Ren Gang , Dahl Jeremy , Thakor Avnesh S.
Published: September 2019

This study demonstrates that pulsed focused ultrasound (pFUS) therapy can non-invasively enhance the function and engraftment of pancreatic islets following transplantation.In vitro, we show that islets treated with pFUS at low (peak negative pressure (PNP): 106kPa, spatial peak temporal peak intensity (Isptp): 0.71 W/cm2), medium (PNP: 150kPa, Isptp: 1.43 W/cm2) or high (PNP: 212kPa, Isptp: 2.86 W/cm2) acoustic intensities were stimulated resulting in an increase in their function (i.e. insulin secretion at low-intensity: 1.15 ± 0.17, medium-intensity: 2.02 ± 0.25, and high-intensity: 2.54 ± 0.38 fold increase when compared to control untreated islets; P < 0.05). Furthermore, we have shown that this improvement in islet function is a result of pFUS increasing the intracellular concentration of calcium (Ca2+) within islets which was also linked to pFUS increasing the resting membrane potential (Vm) of islets. Following syngeneic renal sub-capsule islet transplantation in C57/B6 mice, pFUS (PNP: 2.9 MPa, Isptp: 895 W/cm2) improved the function of transplanted islets with diabetic animals rapidly re-establishing glycemic control. In addition, pFUS was able to enhance the engraftment by facilitating islet revascularization and reducing inflammation. Given a significant number of islets are lost immediately following transplantation, pFUS has the potential to be used in humans as a novel non-invasive therapy to facilitate islet function and engraftment, thereby improving the outcome of diabetic patients undergoing islet transplantation.
A novel automated image analysis system using deep convolutional neural networks can assist to differentiate MDS and AA
Authors: Kimura Konobu , Tabe Yoko , Ai Tomohiko , Takehara Ikki , Fukuda Hiroshi , Takahashi Hiromizu , Naito Toshio , Komatsu Norio , Uchihashi Kinya , Ohsaka Akimichi
Published: September 2019

Detection of dysmorphic cells in peripheral blood (PB) smears is essential in diagnostic screening of hematological diseases. Myelodysplastic syndromes (MDS) are hematopoietic neoplasms characterized by dysplastic and ineffective hematopoiesis, which diagnosis is mainly based on morphological findings of PB and bone marrow. We developed an automated diagnostic support system of MDS by combining an automated blood cell image-recognition system using a deep learning system (DLS) powered by convolutional neural networks (CNNs) with a decision-making system using extreme gradient boosting (XGBoost). The DLS of blood cell image-recognition has been trained using datasets consisting of 695,030 blood cell images taken from 3,261 PB smears including hematopoietic malignancies. The DLS simultaneously classified 17 blood cell types and 97 morphological features of such cells with >93.5% sensitivity and >96.0% specificity. The automated MDS diagnostic system successfully differentiated MDS from aplastic anemia (AA) with high accuracy; 96.2% of sensitivity and 100% of specificity (AUC 0.990). This is the first CNN-based automated initial diagnostic system for MDS using PB smears, which is applicable to develop new automated diagnostic systems for various hematological disorders.
Ultrasound remission can predict future good structural outcome in collagen-induced arthritis rats
Authors: Li Wenxue , Liu Yiqun , Zhu Jiaan , Bilig Arong , Liu Fang , Chen Zheng
Published: September 2019

Regarding the persistence of subclinical synovitis, the concept of ultrasound remission has been proposed in addition to clinical remission. The present study aims to explore whether ultrasound remission has predictive value and ultrasound remission at which time point has predictive value for good structural outcome. Collagen-induced arthritis (CIA) was induced in 32 rats by immunizing with bovine type II collagen. Twenty-four CIA rats were treated with rhTNFR:Fc, and 8 rats were left untreated. Ultrasonography was performed to assess synovial hypertrophy, power Doppler (PD) signal, and bone erosion of the ankle joints of both hindpaws every week following the booster immunization. In the treated group, the scores for synovial hypertrophy, PD signal and bone erosions decreased from baseline to the end. Synovial hypertrophy, PD signal, and bone erosion at baseline were not significantly associated with good structural outcome. Ultrasound remission from 4 to 6 weeks after treatment was significantly associated with good outcome and had the highest area under the curve, sensitivity, specificity, and positive and negative predictive values. Therefore, we conclude that ultrasound remission from 4 to 6 weeks after treatment has a high value for predicting good structural outcome in CIA rats.
Genomic Characterization of Diverse Gyroviruses Identified in the Feces of Domestic Cats
Authors: Niu Jiang-Ting , Yi Shu-Shuai , Dong Guo-Ying , Guo Yan-Bing , Zhao Yan-Li , Huang Hai-Long , Wang Kai , Hu Gui-Xue , Dong Hao
Published: September 2019

Gyroviruses (GyVs) are small, single-stranded, circular DNA viruses in the genus Gyrovirus, which consists of the chicken anemia virus (CAV) prototype and nine other viral species. These different GyV species have been reported in chickens, humans, mice, and companion animals. To date, CAV has been identified in the feces of domestic cats, while the circulation of other GyV species in cats is currently unknown. In the present study, 197 fecal samples were collected from pet cats in northeast China, and samples were screened for different GyV species by PCR. Twelve GyV strains were identified from the feces of pet cats. These included 4 positive for CAV, 3 for HGyV/AGV2, 3 for GyV3 and 2 positive for GyV6. The complete genome sequences of the 12 cat-sourced GyV strains showed 93.9–99.7% nucleotide identities to the homologous reference GyV strains. Phylogenetic analyses based on the complete genomes, VP1, VP2 and VP3 genes showed the identical classification of GyV species with previous reports. Moreover, one and four unique amino acid substitutions were identified in the VP1 protein of the cat-sourced HGyV/AGV2 and GyV6 strains, respectively, and one substitution was also observed in the VP2 protein of one GyV6 strain identified in this study. In conclusion, our investigation demonstrates that the diverse GyV species were circulating in domestic cats, and provides the first molecular evidence for the circulation of HGyV/AGV2, GyV3 and GyV6 in domestic cats. These cat-origin GyVs possessed considerable genetic diversity. This study also raises the possibility that domestic cats, as reservoirs for gyroviruses, may inadvertently disseminate viruses to other species, e.g., humans and chickens.
Gut microbiome comparability of fresh-frozen versus stabilized-frozen samples from hospitalized patients using 16S rRNA gene and shotgun metagenomic sequencing
Authors: Ilett Emma E. , Jørgensen Mette , Noguera-Julian Marc , Daugaard Gedske , Murray Daniel D. , Helleberg Marie , Paredes Roger , Lundgren Jens , Sengeløv Henrik , MacPherson Cameron
Published: September 2019

Collection of faecal samples for microbiome analysis in acutely sick patients is logistically difficult, particularly if immediate freezing is required (i.e. fresh-frozen, or FF sampling). Previous studies in healthy/non-hospitalized volunteers have shown that chemical stabilization (i.e. stabilized-frozen, or SF sampling) allows room-temperature storage with comparable results to FF samples. To test this in a hospital setting we compared FF and SF approaches across 17 patients undergoing haematopoietic stem cell transplantation (HSCT) using both 16S rRNA gene and shotgun metagenomic sequencing. A paired (same stool specimen) comparison of FF and SF samples was made, with an overall comparable level in relative taxonomic abundances between the two sampling techniques. Though shotgun metagenomic sequencing found significant differences for certain bacterial genera (P < 0.001), these were considered minor methodological effects. Within-sample diversity of either method was not significantly different (Shannon diversity P16SrRNA = 0.68 and Pshotgun = 0.89) and we could not reject the null hypothesis that between-sample variation in FF and SF were equivalent (P16SrRNA = 0.98 and Pshotgun = 1.0). This indicates that SF samples can be used to reliably study the microbiome in acutely sick patient populations, thus creating and enabling further outcomes-based metagenomic studies on similarly valuable cohorts.