bluuebunny/crossref_metadata_2025_split huggingface dataset:
Internet tools to enhance breast cancer care
Authors: Shachar Shlomit Strulov , Muss Hyman B 
Published: April 2016

AbstractInternet tools have become a great aid in the daily practice of physicians who treat breast cancer patients. In cancer care there are frequent and important intersections where major decisions need to be made; these include (1) whether or not to give chemotherapy; (2) how much toxicity to expect, and (3) the life expectancy of the patient, considering non-breast cancer comorbidities. These decisions can be made more accurately using calculators based on data sets of thousands of patients as opposed to physician intuition. Such tools also help patients and caregivers in optimal decision making, as they estimate the absolute benefits and risks of treatment. In this perspective we describe selected internet sites that are useful across several domains of care, including the potential benefits of different adjuvant regimens for early breast cancer, prognosis after neoadjuvant therapy, prognosis for ductal carcinoma in situ, and toxicity and life expectancy estimates. We review the variables required to use the tools, the results obtained, the methods of validation, and the advantages and disadvantages of each tool.
Type conversion of secretomes in a 3D TAM2 and HCC cell co-culture system and functional importance of CXCL2 in HCC
Authors: Lu Yu , Li Shan , Ma Liping , Li Yan , Zhang Xiaolian , Peng Qiliu , Mo Cuiju , Huang Li , Qin Xue , Liu Yinkun 
Published: April 2016

AbstractMacrophages play important roles in the tumor microenvironment, driving cancer progression and metastasis, particularly in hepatocellular carcinoma (HCC). However, few studies have assessed the exact secretome composition in HCC. In the present study, the impact of different phenotype of macrophages on HCC cells was investigated. Alternatively activated macrophages (M2) were found to significantly increase the proliferation, migration and invasion abilities of SMMC7721 cells (all P < 0.05). M2 were then co-cultured with SMMC7721 cells to reconstruct the tumor microenvironment. Conditioned medium from 3D single cultures of M2, SMMC7721 cells and their co-culture system were analyzed using quantitative proteomics via iTRAQ labeling combined with mass spectrometric analysis. Secretome analysis revealed a total of 159 differential secreted proteins in the co-culture system compared to the single culture systems, with 63 being up-regulated (>1.3-fold) and 96 down-regulated (<0.7-fold). CXCL2 was confirmed to have higher expression in the co-culture system and HCC tissues and was selected for further investigation. Functional effects data suggested that recombinant human CXCL2 significantly enhanced the migration, invasion ability of SMMC7721 cells and weakened adhesion ability. While CXCL2 neutralization and CXCR2 blockage significantly inhibited the effects of CXCL2 on SMMC7721 cells, indicating that CXCL2 may play pivotal role in HCC metastasis.
Protecting enzymatic function through directed packaging into bacterial outer membrane vesicles
Authors: Alves Nathan J. , Turner Kendrick B. , Medintz Igor L. , Walper Scott A. 
Published: April 2016

AbstractBacteria possess innate machinery to transport extracellular cargo between cells as well as package virulence factors to infect host cells by secreting outer membrane vesicles (OMVs) that contain small molecules, proteins and genetic material. These robust proteoliposomes have evolved naturally to be resistant to degradation and provide a supportive environment to extend the activity of encapsulated cargo. In this study, we sought to exploit bacterial OMV formation to package and maintain the activity of an enzyme, phosphotriesterase (PTE), under challenging storage conditions encountered for real world applications. Here we show that OMV packaged PTE maintains activity over free PTE when subjected to elevated temperatures (>100-fold more activity after 14 days at 37 °C), iterative freeze-thaw cycles (3.4-fold post four-cycles) and lyophilization (43-fold). We also demonstrate how lyophilized OMV packaged PTE can be utilized as a cell free reagent for long term environmental remediation of pesticide/chemical warfare contaminated areas.
Substantial and robust changes in microRNA transcriptome support postnatal development of the hypothalamus in rat
Authors: Doubi-Kadmiri Soraya , Benoit Charlotte , Benigni Xavier , Beaumont Guillaume , Vacher Claire-Marie , Taouis Mohammed , Baroin-Tourancheau Anne , Amar Laurence 
Published: April 2016

AbstractMicroRNAs (miRNAs) modulate gene expression in male germ cells and somatic tissues of mammals on a genome-wide scale. Hundreds of miRNAs are encoded by mammalian genomes, a large fraction of which is expressed in brain. Here we have investigated the complexity and dynamics of miRNA transcriptomes that associate with neuronal network maturation of hypothalamic arcuate nucleus and median eminence (ARC/ME) in rat by analysing more than 300 miRNAs from 3–7 biological replicates at 5 postnatal time-points. The network connecting ARC/ME to other hypothalamic and extra-hypothalamic regions maturates in an environment-dependent manner. We therefore analyzed miRNA transcriptomes of progeny of dams fed either a balanced or unbalanced diet during gestation and lactation. More than 30% of the miRNAs displayed significative changes of expression between stages P8 and P14, and P21 and P28; half of the changes were greater than 3-fold. Among those miRNAs were well-known and dozens of still poorly documented miRNAs. Progeny of dams fed an unbanced diet displayed a severe growth retardation phenotype, lower levels of plasma leptin but almost identical miRNA transcriptomes. Together these data demonstrate that two substantial and robust changes in miRNA transcriptome of ARC/ME occur at a period crucial for neuronal network functional organization.
Fingolimod modulates multiple neuroinflammatory markers in a mouse model of Alzheimer’s disease
Authors: Aytan Nurgul , Choi Ji-Kyung , Carreras Isabel , Brinkmann Volker , Kowall Neil W. , Jenkins Bruce G. , Dedeoglu Alpaslan 
Published: April 2016

AbstractSphingosine 1-phosphate (SP1) receptors may be attractive targets for modulation of inflammatory processes in neurodegenerative diseases. Recently fingolimod, a functional S1P1 receptor antagonist, was introduced for treatment of multiple sclerosis. We postulated that anti-inflammatory mechanisms of fingolimod might also be protective in Alzheimer’s disease (AD). Therefore, we treated a mouse model of AD, the 5xFAD model, with two doses of fingolimod (1 and 5 mg/kg/day) and measured the response of numerous markers of Aβ pathology as well as inflammatory markers and neurochemistry using biochemical, immunohistochemistry and high resolution magic angle spinning magnetic resonance spectroscopy (MRS). In mice at 3 months of age, we found that fingolimod decreased plaque density as well as soluble plus insoluble Aβ measured by ELISA. Fingolimod also decreased GFAP staining and the number of activated microglia. Taurine has been demonstrated to play a role as an endogenous anti-inflammatory molecule. Taurine levels, measured using MRS, showed a very strong inverse correlation with GFAP levels and ELISA measurements of Aβ, but not with plaque density or activated microglia levels. MRS also showed an effect of fingolimod on glutamate levels. Fingolimod at 1 mg/kg/day provided better neuroprotection than 5 mg/kg/day. Together, these data suggest a potential therapeutic role for fingolimod in AD.
Virtual Raters for Reproducible and Objective Assessments in Radiology
Authors: Kleesiek Jens , Petersen Jens , Döring Markus , Maier-Hein Klaus , Köthe Ullrich , Wick Wolfgang , Hamprecht Fred A. , Bendszus Martin , Biller Armin 
Published: April 2016

AbstractVolumetric measurements in radiologic images are important for monitoring tumor growth and treatment response. To make these more reproducible and objective we introduce the concept of virtual raters (VRs). A virtual rater is obtained by combining knowledge of machine-learning algorithms trained with past annotations of multiple human raters with the instantaneous rating of one human expert. Thus, he is virtually guided by several experts. To evaluate the approach we perform experiments with multi-channel magnetic resonance imaging (MRI) data sets. Next to gross tumor volume (GTV) we also investigate subcategories like edema, contrast-enhancing and non-enhancing tumor. The first data set consists of N = 71 longitudinal follow-up scans of 15 patients suffering from glioblastoma (GB). The second data set comprises N = 30 scans of low- and high-grade gliomas. For comparison we computed Pearson Correlation, Intra-class Correlation Coefficient (ICC) and Dice score. Virtual raters always lead to an improvement w.r.t. inter- and intra-rater agreement. Comparing the 2D Response Assessment in Neuro-Oncology (RANO) measurements to the volumetric measurements of the virtual raters results in one-third of the cases in a deviating rating. Hence, we believe that our approach will have an impact on the evaluation of clinical studies as well as on routine imaging diagnostics.
Long-term effects of cerebral hypoperfusion on neural density and function using misery perfusion animal model
Authors: Nishino Asuka , Tajima Yosuke , Takuwa Hiroyuki , Masamoto Kazuto , Taniguchi Junko , Wakizaka Hidekatsu , Kokuryo Daisuke , Urushihata Takuya , Aoki Ichio , Kanno Iwao , Tomita Yutaka , Suzuki Norihiro , Ikoma Yoko , Ito Hiroshi 
Published: April 2016

AbstractWe investigated the chronic effects of cerebral hypoperfusion on neuronal density and functional hyperemia using our misery perfusion mouse model under unilateral common carotid artery occlusion (UCCAO). Neuronal density evaluated 28 days after UCCAO using [11C]flumazenil-PET and histology indicated no neurologic deficit in the hippocampus and neocortex. CBF response to sensory stimulation was assessed using laser-Doppler flowmetry. Percentage changes in CBF response of the ipsilateral hemisphere to UCCAO were 18.4 ± 3.0%, 6.9 ± 2.8%, 6.8 ± 2.3% and 4.9 ± 2.4% before and 7, 14 and 28 days after UCCAO, respectively. Statistical significance was found at 7, 14 and 28 days after UCCAO (P < 0.01). Contrary to our previous finding (Tajima et al. 2014) showing recovered CBF response to hypercapnia on 28 days after UCCAO using the same model, functional hyperemia was sustained and became worse 28 days after UCCAO.
Effects of germination season on life history traits and on transgenerational plasticity in seed dormancy in a cold desert annual
Authors: Lu Juan J. , Tan Dun Y. , Baskin Carol C. , Baskin Jerry M. 
Published: April 2016

AbstractThe maternal environment can influence the intensity of seed dormancy and thus seasonal germination timing and post-germination life history traits. We tested the hypotheses that germination season influences phenotypic expression of post-germination life history traits in the cold desert annualIsatis violascensand that plants from autumn- and spring-germinating seeds produce different proportions of seeds with nondeep and intermediate physiological dormancy (PD). Seeds were sown in summer and flexibility in various life history traits determined for plants that germinated in autumn and in spring. A higher percentage of spring- than of autumn-germinating plants survived the seedling stage and all surviving plants reproduced. Number of silicles increased with plant size (autumn- > spring-germinating plants), whereas percent dry mass allocated to reproduction was higher in spring- than in autumn-germinating plants. Autumn-germinating plants produced proportionally more seeds with intermediate PD than spring-germinating plants, while spring-germinating plants produced proportionally more seeds with nondeep PD than autumn-germinating plants. Flexibility throughout the life history and transgenerational plasticity in seed dormancy are adaptations ofI. violascensto its desert habitat. Our study is the first to demonstrate that autumn- and spring-germinating plants in a species population differ in proportion of seeds produced with different levels of PD.
Terminalia Chebula provides protection against dual modes of necroptotic and apoptotic cell death upon death receptor ligation
Authors: Lee Yoonjung , Byun Hee Sun , Seok Jeong Ho , Park Kyeong Ah , Won Minho , Seo Wonhyoung , Lee So-Ra , Kang Kidong , Sohn Kyung-Cheol , Lee Ill Young , Kim Hyeong-Geug , Son Chang Gue , Shen Han-Ming , Hur Gang Min 
Published: April 2016

AbstractDeath receptor (DR) ligation elicits two different modes of cell death (necroptosis and apoptosis) depending on the cellular context. By screening a plant extract library from cells undergoing necroptosis or apoptosis, we identified a water extract of Terminalia chebula (WETC) as a novel and potent dual inhibitor of DR-mediated cell death. Investigation of the underlying mechanisms of its anti-necroptotic and anti-apoptotic action revealed that WETC or its constituents (e.g., gallic acid) protected against tumor necrosis factor-induced necroptosis via the suppression of TNF-induced ROS without affecting the upstream signaling events. Surprisingly, WETC also provided protection against DR-mediated apoptosis by inhibition of the caspase cascade. Furthermore, it activated the autophagy pathway via suppression of mTOR. Of the WETC constituents, punicalagin and geraniin appeared to possess the most potent anti-apoptotic and autophagy activation effect. Importantly, blockage of autophagy with pharmacological inhibitors or genetic silencing of Atg5 selectively abolished the anti-apoptotic function of WETC. These results suggest that WETC protects against dual modes of cell death upon DR ligation. Therefore, WETC might serve as a potential treatment for diseases characterized by aberrantly sensitized apoptotic or non-apoptotic signaling cascades.
Low-temperature catalytic oxidative coupling of methane in an electric field over a Ce–W–O catalyst system
Authors: Sugiura Kei , Ogo Shuhei , Iwasaki Kousei , Yabe Tomohiro , Sekine Yasushi 
Published: April 2016

AbstractWe examined oxidative coupling of methane (OCM) over various Ce–W–O catalysts at 423 K in an electric field. Ce2(WO4)3/CeO2 catalyst showed high OCM activity. In a periodic operation test over Ce2(WO4)3/CeO2 catalyst, C2 selectivity exceeded 60% during three redox cycles. However, Ce2(WO4)3/CeO2 catalyst without the electric field showed low activity, even at 1073 K: CH4 Conv., 6.0%; C2 Sel., 2.1%. A synergetic effect between the Ce2(WO4)3 structure and electric field created the reactive oxygen species for selective oxidation of methane. Results of XAFS, in-situ Raman and periodic operation tests demonstrated that OCM occurred as the lattice oxygen in Ce2(WO4)3 (short W–O bonds in distorted WO4 unit) was consumed. The consumed oxygen was reproduced by a redox mechanism in the electric field.
Identification and characterization of rabbit ROSA26 for gene knock-in and stable reporter gene expression
Authors: Yang Dongshan , Song Jun , Zhang Jifeng , Xu Jie , Zhu Tianqing , Wang Zhong , Lai Liangxue , Chen Y. Eugene 
Published: April 2016

AbstractThe laboratory rabbit has been a valuable model system for human disease studies. To make the rabbit model more amendable to targeted gene knockin and stable gene over-expression, we identified a rabbit orthologue of the mouse Rosa26 locus through genomic sequence homology analysis. Real-time PCR and 5′ RACE and 3′ RACE experiments revealed that this locus encodes two transcript variants of a long noncoding RNA (lncRNA) (rbRosaV1 and rbRosaV2). Both variants are expressed ubiquitously and stably in different tissues. We next targeted the rabbit Rosa26 (rbRosa26) locus using CRISPR/Cas9 and produced two lines of knock-in rabbits (rbRosa26-EGFP and rbRosa26-Cre-reporter). In both lines, all the founders and their offspring appear healthy and reproduce normally. In F1 generation animals, the rbRosa26-EGFP rabbits express EGFP and the rbRosa26-Cre-reporter rabbits express tdTomato ubiquitously in all the tissues examined. Furthermore, disruption of rbRosa26 locus does not adversely impact the animal health and reproduction. Therefore, our work establishes rbRosa26 as a safe harbor suitable for nuclease mediated gene targeting. The addition of rbRosa26 to the tool box of transgenic research is expected to allow diverse genetic manipulations, including gain-of function, conditional knock out and lineage-tracing studies in rabbits.
Positional distribution of transcription factor binding sites in Arabidopsis thaliana
Authors: Yu Chun-Ping , Lin Jinn-Jy , Li Wen-Hsiung 
Published: April 2016

AbstractBinding of a transcription factor (TF) to its DNA binding sites (TFBSs) is a critical step to initiate the transcription of its target genes. It is therefore interesting to know where the TFBSs of a gene are likely to locate in the promoter region. Here we studied the positional distribution of TFBSs in Arabidopsis thaliana, for which many known TFBSs are now available. We developed a method to identify the locations of TFBSs in the promoter sequences of genes in A. thaliana. We found that the distribution is nearly bell-shaped with a peak at 50 base pairs (bp) upstream of the transcription start site (TSS) and 86% of the TFBSs are in the region from −1,000 bp to +200 bp with respect to the TSS. Our distribution was supported by chromatin immunoprecipitation sequencing and microarray data and DNase I hypersensitive site sequencing data. When TF families were considered separately, differences in positional preference were observed between TF families. Our study of the positional distribution of TFBSs seems to be the first in a plant.
sFRP4-dependent Wnt signal modulation is critical for bone remodeling during postnatal development and age-related bone loss
Authors: Haraguchi Ryuma , Kitazawa Riko , Mori Kiyoshi , Tachibana Ryosuke , Kiyonari Hiroshi , Imai Yuuki , Abe Takaya , Kitazawa Sohei 
Published: April 2016

AbstractsFRP4 is an extracellular Wnt antagonist that fine-tunes its signal activity by direct binding to Wnts. Bone fragility under oxidative stress by diabetes and aging is partly related to the suppression of the Wnt signal through upregulated sFRP4. Here, to explore the functions of sFRP4 as a balancer molecule in bone development and remodeling, we analyzed the sFRP4 knock-in mouse strain. X-gal and immunohistochemically stained signals in sFRP4-LacZ heterozygous mice were detectable in restricted areas, mostly in osteoblasts and osteoclasts, of the femoral diaphysis after neonatal and postnatal stages. Histological and μCT analyses showed increased trabecular bone mass with alteration of the Wnt signal and osteogenic activity in sFRP4 mutants; this augmented the effect of the buildup of trabecular bone during the ageing period. Our results indicate that sFRP4 plays a critical role in bone development and remodeling by regulating osteoblasts and osteoclasts and that its functional loss prevents age-related bone loss in the trabecular bone area. These findings imply that sFRP4 functions as a key potential endogenous balancer of the Wnt signaling pathway by efficiently having direct influence on both bone formation and bone absorption during skeletal bone development and maintenance through remodeling.
Increased and prolonged human norovirus infection in RAG2/IL2RG deficient gnotobiotic pigs with severe combined immunodeficiency
Authors: Lei Shaohua , Ryu Junghyun , Wen Ke , Twitchell Erica , Bui Tammy , Ramesh Ashwin , Weiss Mariah , Li Guohua , Samuel Helen , Clark-Deener Sherrie , Jiang Xi , Lee Kiho , Yuan Lijuan 
Published: April 2016

AbstractApplication of genetically engineered (GE) large animals carrying multi-allelic modifications has been hampered by low efficiency in production and extended gestation period compared to rodents. Here, we rapidly generated RAG2/IL2RG double knockout pigs using direct injection of CRISPR/Cas9 system into developing embryos. RAG2/IL2RG deficient pigs were immunodeficient, characterized by depletion of lymphocytes and either absence of or structurally abnormal immune organs. Pigs were maintained in gnotobiotic facility and evaluated for human norovirus (HuNoV) infection. HuNoV shedding lasted for 16 days in wild type pigs, compared to 27 days (until the end of trials) in RAG2/IL2RG deficient pigs. Additionally, higher HuNoV titers were detected in intestinal tissues and contents and in blood, indicating increased and prolonged HuNoV infection in RAG2/IL2RG deficient pigs and the importance of lymphocytes in HuNoV clearance. These results suggest that GE immunodeficient gnotobiotic pigs serve as a novel model for biomedical research and will facilitate HuNoV studies.
Interactions between Hatch Dates, Growth Rates, and Mortality of Age‐0 Native Rainbow Smelt and Nonnative Alewife in Lake Champlain
Authors: Simonin Paul W. , Parrish Donna L. , Rudstam Lars G. , Pientka Bernard , Sullivan Patrick J. 
Published: April 2016

AbstractTiming of hatch in fish populations can be critical for first‐year survival and, therefore, year‐class strength and subsequent species interactions. We compared hatch timing, growth rates, and subsequent mortality of age‐0 Rainbow Smelt Osmerus mordax and Alewife Alosa pseudoharengus, two common open‐water fish species of northern North America. In our study site, Lake Champlain, Rainbow Smelt hatched (beginning May 26) almost a month earlier than Alewives (June 20). Abundance in the sampling area was highest in July for age‐0 Rainbow Smelt and August for age‐0 Alewives. Late‐hatching individuals of both species grew faster than those hatching earlier (0.6 mm/d versus 0.4 for Rainbow Smelt; 0.7 mm/d versus 0.6 for Alewives). Mean mortality rate during the first 45 d of life was 3.4%/d for age‐0 Rainbow Smelt and was 5.5%/d for age‐0 Alewives. Alewife mortality rates did not differ with hatch timing but daily mortality rates of Rainbow Smelt were highest for early‐hatching fish. Cannibalism is probably the primary mortality source for age‐0 Rainbow Smelt in this lake. Therefore, hatching earlier may not be advantageous because the overlap of adult and age‐0 Rainbow Smelt is highest earlier in the season. However, Alewives, first documented in Lake Champlain in 2003, may increase the mortality of age‐0 Rainbow Smelt in the summer, which should favor selection for earlier hatching.Received October 16, 2015; accepted January 12, 2016 Published online April 27, 2016
Couple Beads: An Integrated Method of Natural Family Planning
Authors: Mulcaire-Jones George , Fehring Richard J. , Bradshaw Megan , Brower Karen , Lubega Gonzaga , Lubega Paskazia 
Published: April 2016

Various fertility indicators are used by natural family planning methods to identify the fertile and infertile phases of a woman's menstrual cycle: mucus observations, cycle-day probabilities, basal body temperature readings, and hormonal measures of LH and estrogen. Simplified NFP methods generally make use of a single fertility indicator such as cycle-day probabilities (Standard Days Method) or mucus observations (Billings Ovulation Method). The Couple Bead Method integrates the two simplest fertility indicators, cycle-day probabilities and mucus observations, expanding its applicability to all women, regardless of cycle regularity and length. In determining cycle-day probabilities, the Couple Bead Method relies on a new data set from ultrasound-derived determinants of gestational age that more directly define the day of conception and the fertile window. By using a visual-based system of inexpensive colored beads, the Couple Bead Method can be used by couples of all educational and income levels. Lay Summary: Natural family planning methods provide education in regard to the signs of a woman's body which indicate if she is possibly fertile or not. Two important signs are the day of her menstrual cycle and her observations of bleeding and cervical mucus or dryness. The Couple Bead Method teaches a couple how to observe these signs and chart them with a system of colored beads. The Couple Bead Method can be used by women with regular or irregular cycles. The bead sets are inexpensive and consist of a length of plastic cord, colored “pony beads” and safety pins.