bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractThe 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

AbstractGlycemic 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

AbstractTriple-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

AbstractThe 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

AbstractEarly 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

AbstractThis 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

AbstractThe 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

AbstractLimited 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

AbstractPerceiving 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

AbstractIn 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

AbstractThe 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

AbstractHuman 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

AbstractCell 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

AbstractOften 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

AbstractUsing 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.