bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement of copy number variation in single cancer cells using rapid-emulsification digital droplet MDA
Authors: Kim Samuel C. , Premasekharan Gayatri , Clark Iain C. , Gemeda Hawi B. , Paris Pamela L. , Abate Adam R. 
Published: June 2017

AbstractUniform amplification of low-input DNA is important for applications across biology, including single-cell genomics, forensic science, and microbial and viral sequencing. However, the requisite biochemical amplification methods are prone to bias, skewing sequence proportions and obscuring signals relating to copy number. Digital droplet multiple displacement amplification enables uniform amplification but requires expert knowledge of microfluidics to generate monodisperse emulsions. In addition, existing microfluidic methods are tedious and labor intensive for preparing many samples. Here, we introduce rapid-emulsification multiple displacement amplification, a method to generate monodisperse droplets with a hand-held syringe and hierarchical droplet splitter. Although conventional microfluidic devices require >10 min to emulsify a sample, our system requires tens of seconds and yields data of equivalent quality. We demonstrate the approach by using it to accurately measure copy number variation (CNV) in single cancer cells.
A bioinspired and biocompatible ortho-sulfiliminyl phenol synthesis
Authors: Xiong Feng , Lu Liang , Sun Tian-Yu , Wu Qian , Yan Dingyuan , Chen Ying , Zhang Xinhao , Wei Wei , Lu Yi , Sun Wei-Yin , Li Jie Jack , Zhao Jing 
Published: June 2017

AbstractSynthetic methods inspired by Nature often offer unique advantages including mild conditions and biocompatibility with aqueous media. Inspired by an ergothioneine biosynthesis protein EgtB, a mononuclear non-haem iron enzyme capable of catalysing the C–S bond formation and sulfoxidation, herein, we discovered a mild and metal-free C–H sulfenylation/intramolecular rearrangement cascade reaction employing an internally oxidizing O–N bond as a directing group. Our strategy accommodates a variety of oxyamines with good site selectivity and intrinsic oxidative properties. Combining an O–N bond with an X–S bond generates a C–S bond and an S=N bond rapidly. The newly discovered cascade reaction showed excellent chemoselectivity and a wide substrate scope for both oxyamines and sulfenylation reagents. We demonstrated the biocompatibility of the C–S bond coupling reaction by applying a coumarin-based fluorogenic probe in bacterial lysates. Finally, the C–S bond coupling reaction enabled the first fluorogenic formation of phospholipids, which self-assembled to fluorescent vesicles in situ.
Flipping between Polycomb repressed and active transcriptional states introduces noise in gene expression
Authors: Kar Gozde , Kim Jong Kyoung , Kolodziejczyk Aleksandra A. , Natarajan Kedar Nath , Torlai Triglia Elena , Mifsud Borbala , Elderkin Sarah , Marioni John C. , Pombo Ana , Teichmann Sarah A. 
Published: June 2017

AbstractPolycomb repressive complexes (PRCs) are important histone modifiers, which silence gene expression; yet, there exists a subset of PRC-bound genes actively transcribed by RNA polymerase II (RNAPII). It is likely that the role of Polycomb repressive complex is to dampen expression of these PRC-active genes. However, it is unclear how this flipping between chromatin states alters the kinetics of transcription. Here, we integrate histone modifications and RNAPII states derived from bulk ChIP-seq data with single-cell RNA-sequencing data. We find that Polycomb repressive complex-active genes have greater cell-to-cell variation in expression than active genes, and these results are validated by knockout experiments. We also show that PRC-active genes are clustered on chromosomes in both two and three dimensions, and interactions with active enhancers promote a stabilization of gene expression noise. These findings provide new insights into how chromatin regulation modulates stochastic gene expression and transcriptional bursting, with implications for regulation of pluripotency and development.
Prognostic value of CD146 in solid tumor: A Systematic Review and Meta-analysis
Authors: Zeng Ping , Li Hai , Lu Pei-Hua , Zhou Li-Na , Tang Min , Liu Chao-Ying , Chen Min-Bin 
Published: June 2017

AbstractCD146, also known as melanoma cell adhesion molecule, was initially identified as a marker of melanoma progression and metastasis. Recently many clinical studies investigated overexpression of CD146 predict poor prognosis of solid tumor, however, the results was inconclusive, partly due to small numbers of patients included. This present meta-analysis was therefore performed utilizing the results of all clinical studies concerned to determine the prognostic value of CD146 expression in solid tumors. Relevant articles were identified through searching the PubMed, Web of Science and Embase database. In this meta-analysis, 12 studies involving 2,694 participants were included, and we drew the conclusion that strong significant associations between CD146 expression and all endpoints: overall survival (OS) [hazard ratio (HR) = 2.496, 95% confidence interval (95% CI) 2.115–2.946], time to progression (TTP) (HR = 2.445, 95% CI 1.975–3.027). Furthermore, the subgroup analysis revealed that the associations between CD146 overexpression and the outcome endpoints (OS or TTP) were significant in Mongoloid patients and Caucasian patients, as well in patients with lung cancer and digestive system cancer. In conclusion, these results showed that high CD146 was associated with poor survival in human solid tumors. CD146 may be a valuable prognosis predictive biomarker; nevertheless, whether CD146 could be a potential therapeutic target in human solid tumors needs to be further studied.
Efficient and unbiased metagenomic recovery of RNA virus genomes from human plasma samples
Authors: Manso Carmen F. , Bibby David F. , Mbisa Jean L. 
Published: June 2017

AbstractRNA viruses cause significant human pathology and are responsible for the majority of emerging zoonoses. Mainstream diagnostic assays are challenged by their intrinsic diversity, leading to false negatives and incomplete characterisation. New sequencing techniques are expanding our ability to agnostically interrogate nucleic acids within diverse sample types, but in the clinical setting are limited by overwhelming host material and ultra-low target frequency. Through selective host RNA depletion and compensatory protocol adjustments for ultra-low RNA inputs, we are able to detect three major blood-borne RNA viruses – HIV, HCV and HEV. We recovered complete genomes and up to 43% of the genome from samples with viral loads of 104 and 103 IU/ml respectively. Additionally, we demonstrated the utility of this method in detecting and characterising members of diverse RNA virus families within a human plasma background, some present at very low levels. By applying this method to a patient sample series, we have simultaneously determined the full genome of both a novel subtype of HCV genotype 6, and a co-infecting human pegivirus. This method builds upon earlier RNA metagenomic techniques and can play an important role in the surveillance and diagnostics of blood-borne viruses.
Size-dependent validation of MODIS MCD64A1 burned area over six vegetation types in boreal Eurasia: Large underestimation in croplands
Authors: Zhu Chunmao , Kobayashi Hideki , Kanaya Yugo , Saito Masahiko 
Published: June 2017

AbstractPollutants emitted from wildfires in boreal Eurasia can be transported to the Arctic, and their subsequent deposition could accelerate global warming. The Moderate Resolution Imaging Spectroradiometer (MODIS) MCD64A1 burned area product is the basis of fire emission products. However, uncertainties due to the “moderate resolution” (500 m) characteristic of the MODIS sensor could be introduced. Here, we present a size-dependent validation of MCD64A1 with reference to higher resolution (better than 30 m) satellite products (Landsat 7 ETM+, RapidEye, WorldView-2, and GeoEye-1) for six ecotypes over 12 regions of boreal Eurasia. We considered the 2012 boreal Eurasia burning season when severe wildfires occurred and when Arctic sea ice extent was historically low. Among the six ecotypes, we found MCD64A1 burned areas comprised only 13% of the reference products in croplands because of inadequate detection of small fires (<100 ha). Our results indicate that over all ecotypes, the actual burned area in boreal Eurasia (15,256 km2) could have been ~16% greater than suggested by MCD64A1 (13,187 km2) when applying the correction factors proposed in this study. This implies the effects of wildfire emissions in boreal Eurasia on Arctic warming could be greater than currently estimated.
A comparison between sphere and rod nanoparticles regarding their in vivo biological behavior and pharmacokinetics
Authors: Zhao Yating , Wang Yu , Ran Fu , Cui Yu , Liu Chang , Zhao Qinfu , Gao Yikun , Wang Da , Wang Siling 
Published: June 2017

AbstractIn recent years, spherical nanoparticles has been studied extensively on biomedical applications including bioimaging and biosensing, diagnostics and theranostics, but the effect of the shape of nanoparticles has received little attention. In the present study, we designed three different shaped fluorescent mesoporous silica nanoparticles (MSNs), long rod nanoparticles (NLR), short rod nanoparticles (NSR), and spherical nanoparticles (NS) to systematically examine their behavior in vivo after oral administration. The results of the ex vivo optical imaging study in mice indicated that rod nanoparticles had a longer residence time in the gastrointestinal compared with spherical nanoparticles. The in vivo biodistribution showed that all the orally administered MSNs were mainly taken up by the liver, and kidney. NLR had a great capacity to overcoming rapid clearance by the RES and exhibited a longer circulation in the blood than NSR and NS. During renal excretion, the spherical nanoparticles were cleared faster than rod nanoparticles. In addition, it was also found that MSNs can be degraded in vivo and NSR were degraded faster than NLR and NS probably owing to their higher specific surface area. The pharmacokinetic results demonstrated that nifedipine(NI)-loaded NLR had a higher bioavailability than NI-loaded NSR and NS.
Mahanine exerts in vitro and in vivo antileishmanial activity by modulation of redox homeostasis
Authors: Roy Saptarshi , Dutta Devawati , Satyavarapu Eswara M. , Yadav Pawan K. , Mandal Chhabinath , Kar Susanta , Mandal Chitra 
Published: June 2017

AbstractEarlier we have established a carbazole alkaloid (mahanine) isolated from an Indian edible medicinal plant as an anticancer agent with minimal effect on normal cells. Here we report for the first time that mahanine-treated drug resistant and sensitive virulent Leishmania donovani promastigotes underwent apoptosis through phosphatidylserine externalization, DNA fragmentation and cell cycle arrest. An early induction of reactive oxygen species (ROS) suggests that the mahanine-induced apoptosis was mediated by oxidative stress. Additionally, mahanine-treated Leishmania-infected macrophages exhibited anti-amastigote activity by nitric oxide (NO)/ROS generation along with suppression of uncoupling protein 2 and Th1-biased cytokines response through modulating STAT pathway. Moreover, we have demonstrated the interaction of a few antioxidant enzymes present in parasite with mahanine through molecular modeling. Reduced genetic and protein level expression of one such enzyme namely ascorbate peroxidase was also observed in mahanine-treated promastigotes. Furthermore, oral administration of mahanine in acute murine model exhibited almost complete reduction of parasite burden, upregulation of NO/iNOS/ROS/IL-12 and T cell proliferation. Taken together, we have established a new function of mahanine as a potent antileishmanial molecule, capable of inducing ROS and exploit antioxidant enzymes in parasite along with modulation of host’s immune response which could be developed as an inexpensive and nontoxic therapeutics either alone or in combination.
High-resolution 3D visualization of ductular proliferation of bile duct ligation-induced liver fibrosis in rats using x-ray phase contrast computed tomography
Authors: Qin Lili , Zhao Xinyan , Jian Jianbo , Zhao Yuqing , Sun Mengyu , Hu Chunhong 
Published: June 2017

AbstractX-ray phase-contrast computed tomography (PCCT) can provide excellent image contrast for soft tissues with small density differences, and it is particularly appropriate for three-dimensional (3D) visualization of accurate microstructures inside biological samples. In this study, the morphological structures of proliferative bile ductules (BDs) were visualized without contrast agents via PCCT with liver fibrosis samples induced by bile duct ligation (BDL) in rats. Adult male Sprague-Dawley rats were randomly divided into three groups: sham operation group, 2-week and 6-week post-BDL groups. All livers were removed after euthanasia for a subsequent imaging. The verification of the ductular structures captured by PCCT was achieved by a careful head-to-head comparison with their corresponding histological images. Our experimental results demonstrated that PCCT images corresponded very well to the proliferative BDs shown by histological staining using cytokeratin 19 (CK19). Furthermore, the 3D density of proliferative BDs increased with the progression of liver fibrosis. In addition, PCCT accurately revealed the architecture of proliferative BDs in a 3D fashion, including the ductular ramification, the elongation and tortuosity of the branches, and the corrugations of the luminal duct surface. Thus, the high-resolution PCCT technique can improve our understanding of the characteristics of ductular proliferation from a new 3D perspective.
Direct observation of a non-crystalline state of Li2S–P2S5 solid electrolytes
Authors: Tsukasaki Hirofumi , Mori Shigeo , Morimoto Hideyuki , Hayashi Akitoshi , Tatsumisago Masahiro 
Published: June 2017

AbstractThere are two types of solid electrolytes which has been recently expected to be applied to all-solid-state batteries. One is the glasses characterized by an amorphous state. The other is the glass ceramics containing crystalline in an amorphous matrix. However, the non-crystalline state of glasses and glass ceramics is still an open question. It has been anticipated that sea-island and core-shell structures including crystalline nanoparticles have been proposed as candidate models for glass ceramics. Nevertheless, no direct observation has been conducted so far. Here we report the non-crystalline state of Li2S–P2S5 glasses and glass ceramics, and the crystallization behavior of the glasses during heating via direct transmission electron microscopy (TEM) observation. High resolution TEM images clearly revealed the presence of crystalline nanoparticles in an amorphous region. Eventually we suggest that the precipitation and connection of crystalline nanoparticles in an amorphous matrix are key to achieving high ionic conductivity.
High-intensity Interval Training Improves Mitochondrial Function and Suppresses Thrombin Generation in Platelets undergoing Hypoxic Stress
Authors: Wu Li-Hua , Chang Shao-Chiang , Fu Tieh-Cheng , Huang Ching-Hui , Wang Jong-Shyan 
Published: June 2017

AbstractThis study elucidates how high-intensity interval training (HIT) and moderate-intensity continuous training (MCT) affect mitochondrial functionality and thrombin generation (TG) in platelets following hypoxic exercise (HE, 100 W under 12% O2 for 30 min). Forty-five healthy sedentary males were randomized to engage either HIT (3-minute intervals at 40% and 80%VO2max, n = 15) or MCT (sustained 60%VO2max, n = 15) for 30 minutes/day, 5 days/week for 6 weeks, or to a control group (CTL, n = 15) that did not received exercise intervention. Before the intervention, HE (i) reduced the ATP-linked O2 consumption rate (OCR), the reserve capacity of OCR, and the activities of citrate synthase (CS) and succinate dehydrogenase (SDH), (ii) lowered mitochondrial membrane potential (MP) and elevated matrix oxidant burden (MOB) in platelets, and (iii) enhanced dynamic TG in platelet-rich plasma (PRP), which responses were attenuated by pretreating PRP with oligomycin or rotenone/antimycin A. However, 6-week HIT (i) increased mitochondrial OCR capacity with enhancing the CS and SDH activities and (ii) heightened mitochondrial MP with depressing MOB in platelets following HE, compared to those of MCT and CTL. Moreover, the HIT suppressed the HE-promoted dynamic TG in PRP. Hence, we conclude that the HIT simultaneously improves mitochondrial bioenergetics and suppresses dynamic TG in platelets undergoing hypoxia.
YvcK, a protein required for cell wall integrity and optimal carbon source utilization, binds uridine diphosphate-sugars
Authors: Foulquier Elodie , Galinier Anne 
Published: June 2017

AbstractIn Bacillus subtilis, Listeria monocytogenes and in two Mycobacteria, it was previously shown that yvcK is a gene required for normal cell shape, for optimal carbon source utilization and for virulence of pathogenic bacteria. Here we report that the B. subtilis protein YvcK binds to Uridine diphosphate-sugars like Uridine diphosphate-Glucose (UDP-Glc) and Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) in vitro. Using the crystal structure of Bacillus halodurans YvcK, we identified residues involved in this interaction. We tested the effect of point mutations affecting the ability of YvcK to bind UDP-sugars on B. subtilis physiology and on cell size. Indeed, it was shown that UDP-Glc serves as a metabolic signal to regulate B. subtilis cell size. Interestingly, we observed that, whereas a yvcK deletion results in the formation of unusually large cells, inactivation of YvcK UDP-sugar binding site does not affect cell length. However, these point mutations result in an increased sensitivity to bacitracin, an antibiotic which targets peptidoglycan synthesis. We thus propose that UDP-GlcNAc, a precursor of peptidoglycan, could be a good physiological ligand candidate of YvcK.
Breast Cancer Multi-classification from Histopathological Images with Structured Deep Learning Model
Authors: Han Zhongyi , Wei Benzheng , Zheng Yuanjie , Yin Yilong , Li Kejian , Li Shuo 
Published: June 2017

AbstractAutomated breast cancer multi-classification from histopathological images plays a key role in computer-aided breast cancer diagnosis or prognosis. Breast cancer multi-classification is to identify subordinate classes of breast cancer (Ductal carcinoma, Fibroadenoma, Lobular carcinoma, etc.). However, breast cancer multi-classification from histopathological images faces two main challenges from: (1) the great difficulties in breast cancer multi-classification methods contrasting with the classification of binary classes (benign and malignant), and (2) the subtle differences in multiple classes due to the broad variability of high-resolution image appearances, high coherency of cancerous cells, and extensive inhomogeneity of color distribution. Therefore, automated breast cancer multi-classification from histopathological images is of great clinical significance yet has never been explored. Existing works in literature only focus on the binary classification but do not support further breast cancer quantitative assessment. In this study, we propose a breast cancer multi-classification method using a newly proposed deep learning model. The structured deep learning model has achieved remarkable performance (average 93.2% accuracy) on a large-scale dataset, which demonstrates the strength of our method in providing an efficient tool for breast cancer multi-classification in clinical settings.
Homing of Cultured Endothelial Progenitor Cells and Their Effect on Traumatic Brain Injury in Rat Model
Authors: Guo Xin-bin , Deng Xin , Wei Ying 
Published: June 2017

AbstractTransplanted endothelial progenitor cells (EPCs) may play an important role in reestablishing the endothelial integrity of the vessels after brain injury, and contribute to neurogenesis. We, therefore, tested the homing of ex vivo cultured peripheral blood-derived EPCs and their effect on injured brain tissue after intravenous administration. To track the homing of implanted EPCs in injured brain tissues, EPCs were labeled with DAPI and BrdU in vitro before transplantation. EPCs were transplanted into the host animal through peripheral administration through the femoral vein, and homing of EPCs was evaluated. The integration of intravenously injected EPCs into the injured brain tissue was demonstrated. Immunohistochemical staining showed that microvessel density in the perifocal region of EPCs-transplanted rats was significantly increased, and the numbers of BrdU+ cells in the DG of subventricular zone were increased in EPCs-transplanted rats as compared to the control group. Transplanted EPCs may play an important role in reestablishing the endothelial integrity in the vessels after brain injury and further contribute to neurogenesis. EPCs enhanced recovery following brain injury in a rat model of TBI.
Upregulate KIF4A Enhances Proliferation, Invasion of Hepatocellular Carcinoma and Indicates poor prognosis Across Human Cancer Types
Authors: Hou Guojun , Dong Chuanpeng , Dong Zihui , Liu Gang , Xu Huilin , Chen Lei , Liu Lei , Wang Hongyang , Zhou Weiping 
Published: June 2017

AbstractHepatocellular carcinoma (HCC) is one of the most aggressive and heterogeneous cancers worldwide. Herein, we demonstrate KIF4A (Chromosome-associated kinesin KIF4A) as a potential biomarker, is up-regulated in most samples of HCC. The expression level of KIF4A in tumor tissue is significantly associated with the survival time, and a significant correlation between KIF4A expression and clinical information stage, metastasis and tumor dimension was observed. We further measured the proliferation and migration ability of two HCC cell lines, HCC-LM3 and PLC/PRF/5, following KIF4A-siRNA transfection. Knocking down of KIF4A significantly reduced migration and proliferation ability. Moreover, we also measured the proliferation and migration ability of two HCC cell lines through KIF4A overexpression, and found that KIF4A overexpression could enhance migration and proliferation ability, indicating that KIF4A exhibits oncogenic effects. Besides, study based on TCGA cohorts also reveals high KIF4A mRNA expression are significantly associated with shorter overall survival in multiple cancer types. Gene sets enrichment analysis exhibited that cell cycle related pathways and p53 signaling pathways to be top altered pathways of in KIF4A-high expression group in HCC, suggesting the potential role of KIF4A in mediating tumor initiation and progression. In summary, our work identified KIF4A as a potential predictive and prognostic marker for hepatocellular carcinoma.