bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular characterization of S. japonicum exosome-like vesicles reveals their regulatory roles in parasite-host interactions
Authors: Zhu Lihui , Liu Juntao , Dao Jinwei , Lu Ke , Li Hao , Gu Huiming , Liu Jinming , Feng Xingang , Cheng Guofeng 
Published: May 2016

AbstractSecreted extracellular vesicles play an important role in pathogen-host interactions. Increased knowledge of schistosome extracellular vesicles could provide insights into schistosome-host interactions and enable the development of novel intervention strategies to inhibit parasitic processes and lessen disease transmission. Here, we describe biochemical characterization of Schistosoma japonicum exosome-like vesicles (S. japonicum EVs). A total of 403 proteins were identified in S. japonicum EVs, and bioinformatics analyses indicated that these proteins were mainly involved in binding, catalytic activity, and translation regulatory activity. Next, we characterized the population of small RNAs associated with S. japonicum EVs. Further studies demonstrated that mammalian cells could internalize S. japonicum EVs and transfer their cargo miRNAs to recipient cells. Additionally, we found that a specific miRNA, likely originating from a final host, ocu-miR-191–5p, is also associated with S. japonicum EVs. Overall, our findings demonstrate that S. japonicum EVs could be implicated in the pathogenesis of schistosomiasis via a mechanism involving the transfer of their cargo miRNAs to hosts. Our findings provide novel insights into the mechanisms of schistosome-host interactions.
Efficient production of cynomolgus monkeys with a toolbox of enhanced assisted reproductive technologies
Authors: Ma Yunhan , Li Jiayu , Wang Ge , Ke Qiong , Qiu Sien , Gao Liang , Wan Haifeng , Zhou Yang , Xiang Andy Peng , Huang Qunshan , Feng Guoping , Zhou Qi , Yang Shihua 
Published: May 2016

AbstractThe efficiency of assisted reproductive technologies (ARTs) in nonhuman primates is low due to no screening criterions for selecting sperm, oocyte, and embryo as well as its surrogate mothers. Here we analyzed 15 pairs of pregnant and non-pregnant cynomolgus monkeys, each pair of which received embryos from one batch of fertilized oocytes, and found ratio of endometrial to myometrial thicknesses in abdominal ultrasonic transverse section of uterus is a reliable indicator for selection of recipients for embryo transfer. We performed 305 ovarian stimulations in 128 female cynomolgus monkeys and found that ovarian stimulation can be performed in a whole year and repeated up to six times in the same monkey without deteriorating fertilization potential of eggs until a poor response to stimulation happened. Fertilization can be efficiently achieved with both conventional and piezo-driven intracytoplasmic sperm injection procedures. In semen collection, semen quality is higher with the penile robe electrical stimulus method compared with the rectal probe method. Moreover, caesarean section is an effective strategy for increasing baby survival rates of multiple pregnancies. These findings provide a practical guidance for the efficient use of ARTs, facilitating their use in genetic engineering of macaque monkeys for basic and translational neuroscience research.
The P2X4 receptor is required for neuroprotection via ischemic preconditioning
Authors: Ozaki Tomohiko , Muramatsu Rieko , Sasai Miwa , Yamamoto Masahiro , Kubota Yoshiaki , Fujinaka Toshiyuki , Yoshimine Toshiki , Yamashita Toshihide 
Published: May 2016

AbstractIschemic preconditioning (IPC), a procedure consisting of transient ischemia and subsequent reperfusion, provides ischemic tolerance against prolonged ischemia in the brain. Although the blood flow changes mediated by IPC are primarily perceived by vascular endothelial cells, the role of these cells in ischemic tolerance has not been fully clarified. In this study, we found that the P2X4 receptor, which is abundantly expressed in vascular endothelial cells, is required for ischemic tolerance following middle artery occlusion (MCAO) in mice. Mechanistically, the P2X4 receptor was stimulated by fluid shear stress, which mimics reperfusion, thus promoting the increased expression of osteopontin, a neuroprotective molecule. Furthermore, we found that the intracerebroventricular administration of osteopontin was sufficient to exert a neuroprotective effect mediated by preconditioning-stimulated P2X4 receptor activation. These results demonstrate a novel mechanism whereby vascular endothelial cells are involved in ischemic tolerance.
Macrophage phagocytosis alters the MRI signal of ferumoxytol-labeled mesenchymal stromal cells in cartilage defects
Authors: Nejadnik Hossein , Lenkov Olga , Gassert Florian , Fretwell Deborah , Lam Isaac , Daldrup-Link Heike E. 
Published: May 2016

AbstractHuman mesenchymal stem cells (hMSCs) are a promising tool for cartilage regeneration in arthritic joints. hMSC labeling with iron oxide nanoparticles enables non-invasive in vivo monitoring of transplanted cells in cartilage defects with MR imaging. Since graft failure leads to macrophage phagocytosis of apoptotic cells, we evaluated in vitro and in vivo whether nanoparticle-labeled hMSCs show distinct MR signal characteristics before and after phagocytosis by macrophages. We found that apoptotic nanoparticle-labeled hMSCs were phagocytosed by macrophages while viable nanoparticle-labeled hMSCs were not. Serial MRI scans of hMSC transplants in arthritic joints of recipient rats showed that the iron signal of apoptotic, nanoparticle-labeled hMSCs engulfed by macrophages disappeared faster compared to viable hMSCs. This corresponded to poor cartilage repair outcomes of the apoptotic hMSC transplants. Therefore, rapid decline of iron MRI signal at the transplant site can indicate cell death and predict incomplete defect repair weeks later. Currently, hMSC graft failure can be only diagnosed by lack of cartilage defect repair several months after cell transplantation. The described imaging signs can diagnose hMSC transplant failure more readily, which could enable timely re-interventions and avoid unnecessary follow up studies of lost transplants.
The enzymes LSD1 and Set1A cooperate with the viral protein HBx to establish an active hepatitis B viral chromatin state
Authors: Alarcon Valentina , Hernández Sergio , Rubio Lorena , Alvarez Francisca , Flores Yvo , Varas-Godoy Manuel , De Ferrari Giancarlo V. , Kann Michael , Villanueva Rodrigo A. , Loyola Alejandra 
Published: May 2016

AbstractWith about 350 million people chronically infected around the world hepatitis B is a major health problem. Template for progeny HBV synthesis is the viral genome, organized as a minichromosome (cccDNA) inside the hepatocyte nucleus. How viral cccDNA gene expression is regulated by its chromatin structure; more importantly, how the modulation of this structure impacts on viral gene expression remains elusive. Here, we found that the enzyme SetDB1 contributes to setting up a repressed cccDNA chromatin state. This repressive state is activated by the histone lysine demethylase-1 (LSD1). Consistently, inhibiting or reducing LSD1 levels led to repression of viral gene expression. This correlates with the transcriptionally repressive mark H3K9 methylation and reduction on the activating marks H3 acetylation and H3K4 methylation on viral promoters. Investigating the importance of viral proteins we found that LSD1 recruitment to viral promoters was dependent on the viral transactivator protein HBx. Moreover, the histone methyltransferase Set1A and HBx are simultaneously bound to the core promoter and Set1A expression correlates with cccDNA H3K4 methylation. Our results shed light on the mechanisms of HBV regulation mediated by the cccDNA chromatin structure, offering new therapeutic targets to develop drugs for the treatment of chronically infected HBV patients.
A cross-immunization model for the extinction of old influenza strains
Authors: Uekermann Florian , Sneppen Kim 
Published: May 2016

AbstractGiven the frequent mutation of antigenic features, the constancy of genetic and antigenic diversity of influenza within a subtype is surprising. While the emergence of new strains and antigenic features is commonly attributed to selection by the human immune system, the mechanism that ensures the extinction of older strains remains controversial. To replicate this dynamics of replacement current models utilize mechanisms such as short-lived strain-transcending immunity, a direct competition for hosts, stochastic extinction or constrained antigenic evolution. Building on the idea of short-lived immunity we introduce a minimal model that exhibits the aforementioned dynamics of replacement. Our model relies only on competition due to an antigen specific immune-response in an unconstrained antigenic space. Furthermore the model explains the size of typical influenza epidemics as well as the tendency that new epidemics are associated with mutations of old antigens.
Plant phosphomannose isomerase as a selectable marker for rice transformation
Authors: Hu Lei , Li Hao , Qin Ruiying , Xu Rongfang , Li Juan , Li Li , Wei Pengcheng , Yang Jianbo 
Published: May 2016

AbstractThe E. coli phosphomannose isomerase (EcPMI) gene is widely used as a selectable marker gene (SMG) in mannose (Man) selection-based plant transformation. Although some plant species exhibit significant PMI activity and active PMIs were even identified in Man-sensitive plants, whether plant PMIs can be used as SMGs remains unclear. In this study, we isolated four novel PMI genes from Chlorella variabilis and Oryza sativa. Their isoenzymatic activities were examined in vitro and compared with that of EcPMI. The active plant PMIs were separately constructed into binary vectors as SMGs and then transformed into rice via Agrobacterium. In both Indica and Japonica subspecies, our results indicated that the plant PMIs could select and produce transgenic plants in a pattern similar to that of EcPMI. The transgenic plants exhibited an accumulation of plant PMI transcripts and enhancement of the in vivo PMI activity. Furthermore, a gene of interest was successfully transformed into rice using the plant PMIs as SMGs. Thus, novel SMGs for Man selection were isolated from plants and our analysis suggested that PMIs encoding active enzymes might be common in plants and could potentially be used as appropriate genetic elements in cisgenesis engineering.
CAP1 (Cyclase-Associated Protein 1) Exerts Distinct Functions in the Proliferation and Metastatic Potential of Breast Cancer Cells Mediated by ERK
Authors: Zhang Haitao , Zhou Guo-Lei 
Published: May 2016

AbstractThe actin-regulating protein CAP1 is implicated in the invasiveness of human cancers. However, the exact role remains elusive and controversial given lines of conflicting evidence. Moreover, a potential role in the proliferative transformation has largely been overlooked. Further establishing the role and dissecting underlying mechanisms are imperative before targeting CAP1 can become a possibility for cancer treatment. Here we report our findings that CAP1 exerts cell type-dependent functions in the invasiveness of breast cancer cells. Depletion of CAP1 in the metastatic MDA-MB-231 and BT-549 cancer cells stimulated the metastatic potential while it actually inhibited it in the non-metastatic MCF-7 cancer cells or in normal cells. Moreover, we demonstrate functions for CAP1 in cancer cell proliferation and anchorage-independent growth, again in a cell context-dependent manner. Importantly, we identify pivotal roles for the ERK-centered signaling in mediating both CAP1 functions. Phosphor mutants of CAP1 at the S307/S309 regulatory site had compromised rescue effects for both the invasiveness and proliferation in CAP1-knockdown cells, suggesting that CAP1 likely mediates upstream cell signals to control both functions. These novel mechanistic insights may ultimately open up avenues for strategies targeting CAP1 in the treatment of breast cancer, tailored for specific types of the highly diverse disease.
Ringhalexin from Hemachatus haemachatus: A novel inhibitor of extrinsic tenase complex
Authors: Barnwal Bhaskar , Jobichen Chacko , Girish Vallerinteavide Mavelli , Foo Chun Shin , Sivaraman J. , Kini R. Manjunatha 
Published: May 2016

AbstractAnticoagulant therapy is used for the prevention and treatment of thromboembolic disorders. Blood coagulation is initiated by the interaction of factor VIIa (FVIIa) with membrane-bound tissue factor (TF) to form the extrinsic tenase complex which activates FX to FXa. Thus, it is an important target for the development of novel anticoagulants. Here, we report the isolation and characterization of a novel anticoagulant ringhalexin from the venom of Hemachatus haemachatus (African Ringhals Cobra). Amino acid sequence of the protein indicates that it belongs to the three-finger toxin family and exhibits 94% identity to an uncharacterized Neurotoxin-like protein NTL2 from Naja atra. Ringhalexin inhibited FX activation by extrinsic tenase complex with an IC50 of 123.8 ± 9.54 nM. It is a mixed-type inhibitor with the kinetic constants, Ki and Ki’ of 84.25 ± 3.53 nM and 152.5 ± 11.32 nM, respectively. Ringhalexin also exhibits a weak, irreversible neurotoxicity on chick biventer cervicis muscle preparations. Subsequently, the three-dimensional structure of ringhalexin was determined at 2.95 Å resolution. This study for the first time reports the structure of an anticoagulant three-finger toxin. Thus, ringhalexin is a potent inhibitor of the FX activation by extrinsic tenase complex and a weak, irreversible neurotoxin.
Formylpeptide Receptors Promote the Migration and Differentiation of Rat Neural Stem Cells
Authors: Wang Guan , Zhang Liang , Chen Xingxing , Xue Xin , Guo Qiaonan , Liu Mingyong , Zhao Jianhua 
Published: May 2016

AbstractNeural stem cells (NSCs) bear characteristics for proliferation, migration and differentiation into three main neural cell type(s): neurons, astrocytes and/or oligodendrocytes. Formylpeptide receptors (Fprs), belonging to the family of G protein-coupled chemoattractant receptors, have been detected on neurons in the central nervous system (CNS). Here, we report that Fpr1 and Fpr2 are expressed on NSCs as detected with immunohistochemistry, RT-PCR and WB assays. In addition, Fpr1 and Fpr2 promoted NSC migration through F-actin polymerization and skewed NSC differentiation to neurons. Our study demonstrates a unique role of Fpr1 and Fpr2 in NSCs and opens a novel window for cell replacement therapies for brain and spinal cord injury.
Prognostic value of DNA repair based stratification of hepatocellular carcinoma
Authors: Lin Zhuo , Xu Shi-Hao , Wang Hai-Qing , Cai Yi-Jing , Ying Li , Song Mei , Wang Yu-Qun , Du Shan-Jie , Shi Ke-Qing , Zhou Meng-Tao 
Published: May 2016

AbstractAberrant activation of DNA repair is frequently associated with tumor progression and response to therapy in hepatocellular carcinoma (HCC). Bioinformatics analyses of HCC data in the Cancer Genome Atlas (TCGA) were performed to define DNA repair based molecular classification that could predict the prognosis of patients with HCC. Furthermore, we tested its predictive performance in 120 independent cases. Four molecular subgroups were identified on the basis of coordinate DNA repair cluster (CDRC) comprising 15 genes in TCGA dataset. Increasing expression of CDRC genes were significantly associated with TP53 mutation. High CDRC was significantly correlated with advanced tumor grades, advanced pathological stage and increased vascular invasion rate. Multivariate Cox regression analysis indicated that the molecular subgrouping was an independent prognostic parameter for both overall survival (p = 0.004, hazard ratio (HR): 2.989) and tumor-free survival (p = 0.049, HR: 3.366) in TCGA dataset. Similar results were also obtained by analyzing the independent cohort. These data suggest that distinct dysregulation of DNA repair constituents based molecular classes in HCC would be useful for predicting prognosis and designing clinical trials for targeted therapy.
Stabilizing the cold plasma-stimulated medium by regulating medium’s composition
Authors: Yan Dayun , Nourmohammadi Niki , Bian Ka , Murad Ferid , Sherman Jonathan H. , Keidar Michael 
Published: May 2016

AbstractOver past several years, the cold plasma-stimulated medium (PSM) has shown its remarkable anti-cancer capacity in par with the direct cold plasma irradiation on cancer cells or tumor tissues. Independent of the cold plasma device, PSM has noticeable advantage of being a flexible platform in cancer treatment. Currently, the largest disadvantage of PSM is its degradation during the storage over a wide temperature range. So far, to stabilize PSM, it must be remained frozen at −80 °C. In this study, we first reveal that the degradation of PSM is mainly due to the reaction between the reactive species and specific amino acids; mainly cysteine and methionine in medium. Based on this finding, both H2O2 in PSM and the anti-cancer capacity of PSM can be significantly stabilized during the storage at 8 °C and −25 °C for at least 3 days by using phosphate-buffered saline (PBS) and cysteine/methionine-free Dulbecco’s Modified Eagle Medium (DMEM). In addition, we demonstrate that adding a tyrosine derivative, 3-Nitro-L-tyrosine, into DMEM can mitigate the degradation of PSM at 8 °C during 3 days of storage. This study provides a solid foundation for the future anti-cancer application of PSM.
The N-end rule pathway regulates pathogen responses in plants
Authors: de Marchi Rémi , Sorel Maud , Mooney Brian , Fudal Isabelle , Goslin Kevin , Kwaśniewska Kamila , Ryan Patrick T. , Pfalz Marina , Kroymann Juergen , Pollmann Stephan , Feechan Angela , Wellmer Frank , Rivas Susana , Graciet Emmanuelle 
Published: May 2016

AbstractTo efficiently counteract pathogens, plants rely on a complex set of immune responses that are tightly regulated to allow the timely activation, appropriate duration and adequate amplitude of defense programs. The coordination of the plant immune response is known to require the activity of the ubiquitin/proteasome system, which controls the stability of proteins in eukaryotes. Here, we demonstrate that the N-end rule pathway, a subset of the ubiquitin/proteasome system, regulates the defense against a wide range of bacterial and fungal pathogens in the model plantArabidopsis thaliana. We show that this pathway positively regulates the biosynthesis of plant-defense metabolites such as glucosinolates, as well as the biosynthesis and response to the phytohormone jasmonic acid, which plays a key role in plant immunity. Our results also suggest that the arginylation branch of the N-end rule pathway regulates the timing and amplitude of the defense program against the model pathogenPseudomonas syringaeAvrRpm1.
Intravenous Tigecycline Facilitates Cure of Severe Clostridium difficile Infection (CDI) After Failure of Standard Therapy: A Case Report and Literature Review of Tigecycline Use in CDI
Authors: Navalkele Bhagyashri D. , Lerner Stephen A. 
Published: May 2016

Abstract
Standard treatment for severe Clostridium difficile infection (CDI) is oral vancomycin with metronidazole. After failure of this standard regimen, treatment becomes challenging. A young woman treated for septic shock developed CDI. Standard treatment failed and she was ineligible for fecal transplant. Addition of tigecycline to her regimen resulted in cure.
Hepatitis C Is Poorly Associated With Drug Use in Cambodian Americans in Lowell, Massachusetts
Authors: Yu Catherine , Gifford Allen L. , Christiansen Cindy L. , Drainoni Mari-Lynn 
Published: May 2016

Background.  Hepatitis C (HCV) is the most common chronic blood-borne infection in the United States and affects Asian and non-Asian Americans comparably. Injection drug use, the most common national transmission risk, is not as prevalent in Asian-Americans, but prior studies do not include many Cambodian Americans. Lowell, Massachusetts has the second largest population of Cambodian Americans, allowing a direct comparison of HCV-infected Cambodian and non-Cambodian Americans not previously done. Improving our understanding of HCV risks in this unique community may improve their linkage to care.
Methods.  In this cross-sectional study, medical data were collected regarding HCV risk factors for HCV-infected Cambodian and non-Cambodian Americans seen at Lowell Community Health Center from 2009 to 2012.
Results.  Cambodian Americans (n = 128) were older (mean age 53 vs 43 years old) and less likely to be male (41% vs 67%, P &lt; .001) compared with non-Cambodians (n = 541). Cambodians had lower rates of injection drug use (1.6% vs 33.6%, P &lt; .001) and any drug use (2.3% vs 82.1%, P &lt; .001). More Cambodians were born between 1945 and 1965 (66.4% vs 44.5%). Within this birth cohort, more Cambodians had no other risk factor (82% vs 69%, P = .02). Fewer Cambodians had chronic HCV (53% vs 74%, P &lt; .001).
Conclusions.  Birth between 1945 and 1965 was the major HCV risk factor for Cambodian Americans. Cambodians had lower rates of injection drug use or any drug use history. Risk behavior screening fails to describe HCV transmission for Cambodian Americans and creates a barrier to their linkage to care.
A Severe Case of Pigmentary Glaucoma in a Child With a Family History of Pigment Dispersion Syndrome
Authors: Aragno Vittoria , Zeboulon Pierre , Baudouin Christophe , Labbé Antoine 
Published: May 2016

Purpose:
To report a case of severe pigmentary glaucoma (PG) in a 13-year-old boy of a family affected by pigment dispersion syndrome (PDS).

Patients and Methods:
A 13-year-old child was referred to our hospital for severe bilateral glaucoma. A complete ophthalmologic evaluation including refraction, intraocular pressure, central corneal thickness, slit-lamp biomicroscopy, gonioscopy, fundus examination, and ultrasound biomicroscopy was performed. Family members were also examined and a family pedigree was obtained.

Results:
Ophthalmologic examination revealed a severe bilateral PG with Krukenberg spindle and a widely open heavily pigmented iridocorneal angle. Ultrasound biomicroscopy showed a deep anterior chamber with pronounced iris concavity in both eyes. Within his family, his 15-year-old sister and 7-year-old brother were both affected by PDS diagnosed on gonioscopy findings.

Conclusions:
We report for the first time a severe case of pediatric PG with a family history of PDS. This case demonstrates that accurate screening is necessary in cases of familial PDS and PG, even in the pediatric population.