bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stochastic priming and spatial cues orchestrate heterogeneous clonal contribution to mouse pancreas organogenesis
Authors: Larsen Hjalte List , Martín-Coll Laura , Nielsen Alexander Valentin , Wright Christopher V. E. , Trusina Ala , Kim Yung Hae , Grapin-Botton Anne 
Published: September 2017

AbstractSpatiotemporal balancing of cellular proliferation and differentiation is crucial for postnatal tissue homoeostasis and organogenesis. During embryonic development, pancreatic progenitors simultaneously proliferate and differentiate into the endocrine, ductal and acinar lineages. Using in vivo clonal analysis in the founder population of the pancreas here we reveal highly heterogeneous contribution of single progenitors to organ formation. While some progenitors are bona fide multipotent and contribute progeny to all major pancreatic cell lineages, we also identify numerous unipotent endocrine and ducto-endocrine bipotent clones. Single-cell transcriptional profiling at E9.5 reveals that endocrine-committed cells are molecularly distinct, whereas multipotent and bipotent progenitors do not exhibit different expression profiles. Clone size and composition support a probabilistic model of cell fate allocation and in silico simulations predict a transient wave of acinar differentiation around E11.5, while endocrine differentiation is proportionally decreased. Increased proliferative capacity of outer progenitors is further proposed to impact clonal expansion.
Cross-talk between miR-471-5p and autophagy component proteins regulates LC3-associated phagocytosis (LAP) of apoptotic germ cells
Authors: Panneerdoss Subbarayalu , Viswanadhapalli Suryavathi , Abdelfattah Nourhan , Onyeagucha Benjamin C. , Timilsina Santosh , Mohammad Tabrez A. , Chen Yidong , Drake Michael , Vuori Kristiina , Kumar T. Rajendra , Rao Manjeet K. 
Published: September 2017

AbstractPhagocytic clearance of apoptotic germ cells by Sertoli cells is vital for germ cell development and differentiation. Here, using a tissue-specific miRNA transgenic mouse model, we show that interaction between miR-471-5p and autophagy member proteins regulates clearance of apoptotic germ cells via LC3-associated phagocytosis (LAP). Transgenic mice expressing miR-471-5p in Sertoli cells show increased germ cell apoptosis and compromised male fertility. Those effects are due to defective engulfment and impaired LAP-mediated clearance of apoptotic germ cells as miR-471-5p transgenic mice show lower levels of Dock180, LC3, Atg12, Becn1, Rab5 and Rubicon in Sertoli cells. Our results reveal that Dock180 interacts with autophagy member proteins to constitute a functional LC3-dependent phagocytic complex. We find that androgen regulates Sertoli cell phagocytosis by controlling expression of miR-471-5p and its target proteins. These findings suggest that recruitment of autophagy machinery is essential for efficient clearance of apoptotic germ cells by Sertoli cells using LAP.
Tango7 regulates cortical activity of caspases during reaper-triggered changes in tissue elasticity
Authors: Kang Yunsik , Neuman Sarah D. , Bashirullah Arash 
Published: September 2017

AbstractCaspases perform critical functions in both living and dying cells; however, how caspases perform physiological functions without killing the cell remains unclear. Here we identify a novel physiological function of caspases at the cortex of Drosophila salivary glands. In living glands, activation of the initiator caspase dronc triggers cortical F-actin dismantling, enabling the glands to stretch as they accumulate secreted products in the lumen. We demonstrate that tango7, not the canonical Apaf-1-adaptor dark, regulates dronc activity at the cortex; in contrast, dark is required for cytoplasmic activity of dronc during salivary gland death. Therefore, tango7 and dark define distinct subcellular domains of caspase activity. Furthermore, tango7-dependent cortical dronc activity is initiated by a sublethal pulse of the inhibitor of apoptosis protein (IAP) antagonist reaper. Our results support a model in which biological outcomes of caspase activation are regulated by differential amplification of IAP antagonists, unique caspase adaptor proteins, and mutually exclusive subcellular domains of caspase activity.
A comprehensive characterization of PncA polymorphisms that confer resistance to pyrazinamide
Authors: Yadon Adam N. , Maharaj Kashmeel , Adamson John H. , Lai Yi-Pin , Sacchettini James C. , Ioerger Thomas R. , Rubin Eric J. , Pym Alexander S. 
Published: September 2017

AbstractTuberculosis chemotherapy is dependent on the use of the antibiotic pyrazinamide, which is being threatened by emerging drug resistance. Resistance is mediated through mutations in the bacterial gene pncA. Methods for testing pyrazinamide susceptibility are difficult and rarely performed, and this means that the full spectrum of pncA alleles that confer clinical resistance to pyrazinamide is unknown. Here, we performed in vitro saturating mutagenesis of pncA to generate a comprehensive library of PncA polymorphisms resultant from a single-nucleotide polymorphism. We then screened it for pyrazinamide resistance both in vitro and in an infected animal model. We identify over 300 resistance-conferring substitutions. Strikingly, these mutations map throughout the PncA structure and result in either loss of enzymatic activity and/or decrease in protein abundance. Our comprehensive mutational and screening approach should stand as a paradigm for determining resistance mutations and their mechanisms of action.
The expression and function of miR-424 in infantile skin hemangioma and its mechanism
Authors: Yang Lili , Dai Jun , Li Fan , Cheng Henghui , Yan Dan , Ruan Qiurong 
Published: September 2017

AbstractInfantile hemangioma is the most common benign tumor in infants. Many studies have confirmed that basic fibroblast growth factor (bFGF) and its key receptor FGFR1 are highly expressed in hemangioma. Moreover, several miRNAs can regulate angiogenesis. In this regard, miR-424 often plays a role as tumor suppressor gene. This study was designed to investigate the mechanism of miR-424 in infantile skin hemangioma. Our results showed low expression of miR-424 in infantile skin hemangioma tissues, and that miR-424 overexpression downregulated FGFR1 expression in hemangioma-derived endothelial cells, while miR-424 inhibition upregulated FGFR1 expression. Luciferase reporter analysis confirmed that FGFR1 was a target gene of miR-424. CCK-8, flow cytometry, transwell migration and tube formation assays demonstrated that miR-424 overexpression inhibited cell proliferation, migration and tube formation, at least in part by blocking the bFGF/FGFR1 pathway. In contrast, miR-424 inhibition significantly enhanced these functions. Furthermore, miR-424 overexpression significantly inhibited ERK1/2 phosphorylation, whereas miR-424 inhibition enhanced ERK1/2 phosphorylation. In conclusion, miR-424 could suppress the bFGF/FGFR1 pathway, thereby inhibit ERK1/2 phosphorylation, and thus inhibit cell proliferation, migration and tube formation capabilities and the development of infantile skin hemangioma.
Characterization of a new member of Iridoviridae, Shrimp hemocyte iridescent virus (SHIV), found in white leg shrimp (Litopenaeus vannamei)
Authors: Qiu Liang , Chen Meng-Meng , Wan Xiao-Yuan , Li Chen , Zhang Qing-Li , Wang Ruo-Yu , Cheng Dong-Yuan , Dong Xuan , Yang Bing , Wang Xiu-Hua , Xiang Jian-Hai , Huang Jie 
Published: September 2017

AbstractA newly discovered iridescent virus that causes severe disease and high mortality in farmed Litopenaeus vannamei in Zhejiang, China, has been verified and temporarily specified as shrimp hemocyte iridescent virus (SHIV). Histopathological examination revealed basophilic inclusions and pyknosis in hematopoietic tissue and hemocytes in gills, hepatopancreas, periopods and muscle. Using viral metagenomics sequencing, we obtained partial sequences annotated as potential iridoviridae. Phylogenetic analyses using amino acid sequences of major capsid protein (MCP) and ATPase revealed that it is a new iridescent virus but does not belong to the five known genera of Iridoviridae. Transmission electron microscopy showed that the virus exhibited a typical icosahedral structure with a mean diameter of 158.6 ± 12.5 nm (n = 30)(v-v) and 143.6 ± 10.8 nm (n = 30)(f-f), and an 85.8 ± 6.0 nm (n = 30) nucleoid. Challenge tests of L. vannamei via intermuscular injection, per os and reverse gavage all exhibited 100% cumulative mortality rates. The in situ hybridization showed that hemopoietic tissue, gills, and hepatopancreatic sinus were the positively reacting tissues. Additionally, a specific nested PCR assay was developed. PCR results revealed that L. vannamei, Fenneropenaeus chinensis, and Macrobrachium rosenbergii were SHIV-positive, indicating a new threat existing in the shrimp farming industry in China.
Biomimetically engineered Amphotericin B nano-aggregates circumvent toxicity constraints and treat systemic fungal infection in experimental animals
Authors: Zia Qamar , Mohammad Owais , Rauf Mohd Ahmar , Khan Wasi , Zubair Swaleha 
Published: September 2017

AbstractBiomimetic synthesis of nanoparticles offers a convenient and bio friendly approach to fabricate complex structures with sub-nanometer precision from simple precursor components. In the present study, we have synthesized nanoparticles of Amphotericin B (AmB), a potent antifungal agent, using Aloe vera leaf extract. The synthesis of AmB nano-assemblies (AmB-NAs) was established employing spectro-photometric and electron microscopic studies, while their crystalline nature was established by X-ray diffraction. AmB-nano-formulation showed much higher stability in both phosphate buffer saline and serum and exhibit sustained release of parent drug over an extended time period. The as-synthesized AmB-NA possessed significantly less haemolysis as well as nephrotoxicity in the host at par with Ambisome®, a liposomized AmB formulation. Interestingly, the AmB-NAs were more effective in killing various fungal pathogens including Candida spp. and evoked less drug related toxic manifestations in the host as compared to free form of the drug. The data of the present study suggest that biomimetically synthesized AmB-NA circumvent toxicity issues and offer a promising approach to eliminate systemic fungal infections in Balb/C mice.
Two NAD-linked redox shuttles maintain the peroxisomal redox balance in Saccharomyces cerevisiae
Authors: Al-Saryi Nadal A. , Al-Hejjaj Murtakab Y , van Roermund Carlo W. T. , Hulmes Georgia E. , Ekal Lakhan , Payton Chantell , Wanders Ronald J. A. , Hettema Ewald H. 
Published: September 2017

AbstractIn Saccharomyces cerevisiae, peroxisomes are the sole site of fatty acid β-oxidation. During this process, NAD+ is reduced to NADH. When cells are grown on oleate medium, peroxisomal NADH is reoxidised to NAD+ by malate dehydrogenase (Mdh3p) and reduction equivalents are transferred to the cytosol by the malate/oxaloacetate shuttle. The ultimate step in lysine biosynthesis, the NAD+-dependent dehydrogenation of saccharopine to lysine, is another NAD+-dependent reaction performed inside peroxisomes. We have found that in glucose grown cells, both the malate/oxaloacetate shuttle and a glycerol-3-phosphate dehydrogenase 1(Gpd1p)-dependent shuttle are able to maintain the intraperoxisomal redox balance. Single mutants in MDH3 or GPD1 grow on lysine-deficient medium, but an mdh3/gpd1Δ double mutant accumulates saccharopine and displays lysine bradytrophy. Lysine biosynthesis is restored when saccharopine dehydrogenase is mislocalised to the cytosol in mdh3/gpd1Δ cells. We conclude that the availability of intraperoxisomal NAD+ required for saccharopine dehydrogenase activity can be sustained by both shuttles. The extent to which each of these shuttles contributes to the intraperoxisomal redox balance may depend on the growth medium. We propose that the presence of multiple peroxisomal redox shuttles allows eukaryotic cells to maintain the peroxisomal redox status under different metabolic conditions.
Differential Serum Cytokine Profiles in Patients with Chronic Hepatitis B, C, and Hepatocellular Carcinoma
Authors: Estevez Jacqueline , Chen Vincent L. , Podlaha Ondrej , Li Biao , Le An , Vutien Philip , Chang Ellen T. , Rosenberg-Hasson Yael , Jiang Zhaoshi , Pflanz Stefan , Ge Dongliang , Gaggar Anuj , Nguyen Mindie H. 
Published: September 2017

AbstractCytokines play an important role in the pathogenesis of cirrhosis and hepatocellular carcinoma (HCC), most cases of which are related to either hepatitis B virus (HBV) or hepatitis C virus (HCV). Prior studies have examined differences in individual cytokine levels in patients with chronic liver disease, but comprehensive cytokine profiling data across different clinical characteristics are lacking. We examined serum cytokine profiles of 411 patients with HCC (n = 102: 32% HBV, 54% HCV, 14% non-viral) and without HCC (n = 309: 39% HBV, 39% HCV, 22% non-viral). Multiplex analysis (Luminex 200 IS) was used to measure serum levels of 51 common cytokines. Random forest machine learning was used to obtain receiver operator characteristic curves and to determine individual cytokine importance using Z scores of mean fluorescence intensity for individual cytokines. Among HCC and non-HCC patients, cytokine profiles differed between HBV and HCV patients (area under curve (AUC) 0.82 for HCC, 0.90 for non-HCC). Cytokine profiles did not distinguish cirrhotic HBV patients with and without HCC (AUC 0.503) or HCV patients with and without HCC (AUC 0.63). In conclusion, patients with HBV or HCV infection, with or without HCC, have distinctly different cytokine profiles, suggesting potential differences in disease pathogenesis and/or disease characteristics.
The effect of frozen-thawed embryo transfer performed concurrently with hysteroscopy on the reproductive outcomes during assisted reproductive treatments
Authors: Zhu Xiuxian , Ye Hongjuan , Fu Yonglun 
Published: September 2017

AbstractThe uterine environment is vital to the successful conception; recently, hysteroscopy was used to remove uterine anomalies in patients undergoing assisted reproductive treatments in combination with a “freeze-all” strategy. However, the rapid recurrence of uterine anomalies impose a negative impact on pregnancy. A possible way to avoid this issue is to implement frozen-thawed embryo transfer (FET) as soon as possible. Thus, we sought to investigate the impact of performing FET concurrently with hysteroscopy in the same mense on the pregnancy outcome. Patients enrolled were divided into two groups: group 1 (n = 272, FET in this mense) and group 2 (n = 251, FET in the next mense). There were no differences in the clinical pregnancy rate (55.15% vs. 53.78%), implantation rate (39.32% vs. 37.2%), spontaneous miscarriage rate (10% vs. 8.89%), or live birth rate (45.96% vs. 45.02%) when comparing the two groups. Binary logistic regression indicated maternal age was negatively associated with the live birth rate, while FET following hysteroscopy in the same mense had no adverse effects on the live birth rate. Our data indicate performing FET concurrently with hysteroscopy in the same menstrual cycle does not impair the pregnancy outcomes, but additional studies with larger populations are needed to confirm these results.
AS1411 Aptamer-Anionic Linear Globular Dendrimer G2-Iohexol Selective Nano-Theranostics
Authors: Mohammadzadeh Pardis , Cohan Reza Ahangari , Ghoreishi Seyedeh Masoumeh , Bitarafan-Rajabi Ahmad , Ardestani Mehdi Shafiee 
Published: September 2017

AbstractMolecular theranostics is of the utmost interest for diagnosis as well as treatment of different malignancies. In the present study, anionic linear globular dendrimer G2 is employed as a suitable carrier for delivery and AS1411 aptamer is exploited as the targeting agent to carry Iohexol specifically to the human breast cancer cells (MCF-7). Dendrimer G2 was prepared and conjugation of dendrimer and aptamer was carried out thereafter. Based on the data yielded by AFM, morphology of smooth and spherical non-targeted dendrimer changed to the rough aspherical shape when it conjugated. Then, conjugation was confirmed using DLS, ELS and SLS methods. Toxicity on nucleolin positive MCF-7 cells and nucleolin negative HEK-293 cells was assessed by XTT and apoptosis/necrosis assays. In vitro uptake was determined using DAPI-FITC staining and ICP-MS methods. In vivo studies including in vivo CT imaging, pathology and blood tests were done to confirm the imaging ability, bio-safety and targeted nature of the Nano-Theranostics in vivo. In a nutshell, the prepared construction showed promising effects upon decreasing the toxicity of Iohexol on normal cells and accumulation of it in the cancer tumors as well as reducing the number of cancer cells.
The roles of wettability and surface tension in droplet formation during inkjet printing
Authors: He Bing , Yang Sucui , Qin Zhangrong , Wen Binghai , Zhang Chaoying 
Published: September 2017

AbstractThis paper describes a lattice Boltzmann-based binary fluid model for inkjet printing. In this model, a time-dependent driving force is applied to actuate the droplet ejection. As a result, the actuation can be accurately controlled by adjusting the intensity and duration of the positive and negative forces, as well as the idle time. The present model was verified by reproducing the actual single droplet ejection process captured by fast imaging. This model was subsequently used to investigate droplet formation in piezoelectric inkjet printing. It was determined that the wettability of the nozzle inner wall and the surface tension of the ink are vital factors controlling the print quality and speed. Increasing the contact angle of the nozzle inner delays the droplet breakup time and reduces the droplet velocity. In contrast, higher surface tension values promote earlier droplet breakup and faster drop velocity. These results indicate that the hydrophilic modification of the nozzle inner wall and the choice of inks with high surface tensions will improve printing quality.
Activation of miR-34a-5p/Sirt1/p66shc pathway contributes to doxorubicin-induced cardiotoxicity
Authors: Zhu Jie-Ning , Fu Yong-Heng , Hu Zhi-qin , Li Wen-Yu , Tang Chun-Mei , Fei Hong-Wen , Yang Hui , Lin Qiu-xiong , Gou De-Ming , Wu Shu-Lin , Shan Zhi-Xin 
Published: September 2017

AbstractThe molecular mechanisms underlying anthracyclines-induced cardiotoxicity have not been well elucidated. MiRNAs were revealed dysregulated in the myocardium and plasma of rats received Dox treatment. MicroRNA-34a-5p (miR-34a-5p) was verified increased in the myocardium and plasma of Dox-treated rats, but was reversed in rats received Dox plus DEX treatments. Human miR-34a-5p was also observed increased in the plasma of patients with diffuse large B-cell lymphoma after 9- and 16-week epirubicin therapy. Up-regulation of miR-34a-5p was observed in Dox-induced rat cardiomyocyte H9c2 cells. MiR-34a-5p could augment Bax expression, but inhibited Bcl-2 expression, along with the increases of the activated caspase-3 and mitochondrial potentials in H9C2 cells. MiR-34a-5p was verified to modulate Sirt1 expression post-transcriptionally. In parallel to Sirt1 siRNA, miR-34a-5p could enhance p66shc expression, accompanied by increases of Bax and the activated caspase-3 and a decrease of Bcl-2 in H9c2 cells. Moreover, enforced expression of Sirt1 alleviated Dox-induced apoptosis of H9c2 cells, with suppressing levels of p66shc, Bax, the activated caspase-3 and miR-34a-5p, and enhancing Bcl-2 expression. Therefore, miR-34a-5p enhances cardiomyocyte apoptosis by targeting Sirt1, activation of miR-34a-5p/Sirt1/p66shc pathway contributes to Dox-induced cardiotoxicity, and blockage of this pathway represents a potential cardioprotective effect against anthracyclines.
Polydatin inhibits mast cell-mediated allergic inflammation by targeting PI3K/Akt, MAPK, NF-κB and Nrf2/HO-1 pathways
Authors: Ye Jing , Piao Hongmei , Jiang Jingzhi , Jin Guangyu , Zheng Mingyu , Yang Jinshi , Jin Xiang , Sun Tianyi , Choi Yun Ho , Li Liangchang , Yan Guanghai 
Published: September 2017

AbstractPolydatin(PD) shows anti-allergic inflammatory effect, and this study investigated its underlying mechanisms inin vitroandin vivomodels. IgE-mediated passive cutaneous anaphylaxis (PCA) and passive systemic anaphylaxis (PSA) models were used to confirm PD effectin vivo. Various signaling pathway proteins in mast cell were examined. RT-PCR, ELISA and western blotting were applied when appropriate. Activity of Lyn and Fyn kinasesin vitrowas measured using the Kinase Enzyme System. PD dose-dependently reduced the pigmentation of Evans blue in the PCA model and decreased the concentration of serum histamine in PSA model, and attenuated the degranulation of mast cells without generating cytotoxicity. PD decreased pro-inflammatory cytokine expression (TNF-α, IL-4, IL-1β, and IL-8). PD directly inhibited activity of Lyn and Syk kinases and down-regulated downstream signaling pathway including MAPK, PI3K/AKT and NF-kB. In addition, PD also targets Nrf2/HO-1 pathway to inhibit mast cell-derived allergic inflammatory reactions. In conclusion, the study demonstrates that PD is a possible therapeutic candidate for allergic inflammatory diseases. It directly inhibited activity of Lyn and Syk kinases and down-regulates the signaling pathway of MAPK, PI3K/AKT and NF-κB, and up-regulates the signaling pathway of Nrf2/HO-1 to inhibit the degranulation of mast cells.
Correlation between polymorphisms of the NR3C1 gene and glucocorticoid effectiveness in patients with pemphigus vulgaris
Authors: Fang Si-Yue , Li Chun-Lei , Liu Xiao-Song , Chen Feng , Hua Hong 
Published: September 2017

AbstractsGlucocorticoid (GC) resistance is the major obscule in the treatment of pemphigus vulgaris (PV) for both patients and clinicans with unclear mechanism. A hypotheis for this resistance is the mutations or polymorphisms present in the nuclear receptor subfamily 3, group C, member 1 (NR3C1) gene that encodes receptors for steroid hormones. This study aimed to investigate the association between NR3C1 gene polymorphisms and GC effectiveness in PV patients. 94 PV patients (64 GC-sensitive and 30 GC-resistant) and 100 healthy volunteers were enrolled in this case-control study. The genotyping of single nucleotide polymorphisms (SNPs) in BCL1, Arg23Lys, Asn363Ser 1548 t-insert, and le747Met, together with tag-SNP sites of the NR3C1 gene were evaluated. No significant differences were observed in genotypic and allelic frequencies of the 16 SNPs between PV patients and healthy volunteers. However, SNPs rs 11745958 C/T (OR: 8.95) and rs17209237 A/G (OR: 4.07) may be associated with an increased risk of GC resistance, while rs 33388 A/T (OR: 0.45) and rs7701443 A/G (OR: 0.51) may indicate a decreased risk of GC resistance in PV patients. NR3C1 gene variation may be associated with GC resistance in PV patients. More extensive genetic analyses and mechanistic analysis are required for further exploration.