bluuebunny/crossref_metadata_2025_split huggingface dataset:
Convective Instability Associated with the Eastward-Propagating Rainfall Episodes over Eastern China during the Warm Season
Authors: Chen Guixing , Yoshida Ryuhei , Sha Weiming , Iwasaki Toshiki , Qin Huiling 
Published: December 2013

AbstractAnalysis of the latest satellite rainfall and reanalysis datasets from 1998 to 2012 demonstrates that eastward-propagating rainfall episodes, which typically occur in late night and morning, are determinant factors for the rainfall diurnal cycle and climate anomalies over eastern China. The episode growth and propagation are facilitated by an elevated layer of conditionally unstable air in a mesoscale zone at their eastern leading edge. The convective available potential energy (CAPE), despite convection consumption and nocturnal cooling, decreases only from a high value to a moderate one during episode duration. An estimate of the CAPE generation budget suggests that low-level horizontal advection and vertical lifting of the warm moist air can produce sufficient CAPE to balance other stabilization effects, sustaining the mesoscale maximum of convective instability ahead of rainfall episodes. These instability geneses are pronounced at the convection growth stage and linked closely to a mesoscale nocturnal low-level jet. Thus, a proper representation of them in forecast models is essential for improved prediction of the warm-season rainfall.
De novo copy number variations in cloned dogs from the same nuclear donor
Authors: Jung Seung-Hyun , Yim Seon-Hee , Oh Hyun Ju , Park Jung Eun , Kim Min Jung , Kim Geon A , Kim Tae-Min , Kim Jin-Soo , Lee Byeong Chun , Chung Yeun-Jun 
Published: December 2013

Abstract

Background
Somatic mosaicism of copy number variants (CNVs) in human body organs and de novo CNV event in monozygotic twins suggest that de novo CNVs can occur during mitotic recombination. These de novo CNV events are important for understanding genetic background of evolution and diverse phenotypes. In this study, we explored de novo CNV event in cloned dogs with identical genetic background.

Results
We analyzed CNVs in seven cloned dogs using the nuclear donor genome as reference by array-CGH, and identified five de novo CNVs in two of the seven clones. Genomic qPCR, dye-swap array-CGH analysis and B-allele profile analysis were used for their validation. Two larger de novo CNVs (5.2 Mb and 338 Kb) on chromosomes X and 19 in clone-3 were consistently validated by all three experiments. The other three smaller CNVs (sized from 36.1 to76.4 Kb) on chromosomes 2, 15 and 32 in clone-3 and clone-6 were verified by at least one of the three validations. In addition to the de novo CNVs, we identified a 37 Mb-sized copy neutral de novo loss of heterozygosity event on chromosome 2 in clone-6.

Conclusions
To our knowledge, this is the first report of de novo CNVs in the cloned dogs which were generated by somatic cell nuclear transfer technology. To study de novo genetic events in cloned animals can help understand formation mechanisms of genetic variants and their biological implications.
A detailed gene expression study of the Miscanthusgenus reveals changes in the transcriptome associated with the rejuvenation of spring rhizomes
Authors: Barling Adam , Swaminathan Kankshita , Mitros Therese , James Brandon T , Morris Juliette , Ngamboma Ornella , Hall Megan C , Kirkpatrick Jessica , Alabady Magdy , Spence Ashley K , Hudson Matthew E , Rokhsar Daniel S , Moose Stephen P 
Published: December 2013

Abstract

Background
The Miscanthus genus of perennial C4 grasses contains promising biofuel crops for temperate climates. However, few genomic resources exist for Miscanthus, which limits understanding of its interesting biology and future genetic improvement. A comprehensive catalog of expressed sequences were generated from a variety of Miscanthus species and tissue types, with an emphasis on characterizing gene expression changes in spring compared to fall rhizomes.

Results
Illumina short read sequencing technology was used to produce transcriptome sequences from different tissues and organs during distinct developmental stages for multiple Miscanthus species, including Miscanthus sinensis, Miscanthus sacchariflorus, and their interspecific hybrid Miscanthus × giganteus. More than fifty billion base-pairs of Miscanthus transcript sequence were produced. Overall, 26,230 Sorghum gene models (i.e., ~ 96% of predicted Sorghum genes) had at least five Miscanthus reads mapped to them, suggesting that a large portion of the Miscanthus transcriptome is represented in this dataset. The Miscanthus × giganteus data was used to identify genes preferentially expressed in a single tissue, such as the spring rhizome, using Sorghum bicolor as a reference. Quantitative real-time PCR was used to verify examples of preferential expression predicted via RNA-Seq. Contiguous consensus transcript sequences were assembled for each species and annotated using InterProScan. Sequences from the assembled transcriptome were used to amplify genomic segments from a doubled haploid Miscanthus sinensis and from Miscanthus × giganteus to further disentangle the allelic and paralogous variations in genes.

Conclusions
This large expressed sequence tag collection creates a valuable resource for the study of Miscanthus biology by providing detailed gene sequence information and tissue preferred expression patterns. We have successfully generated a database of transcriptome assemblies and demonstrated its use in the study of genes of interest. Analysis of gene expression profiles revealed biological pathways that exhibit altered regulation in spring compared to fall rhizomes, which are consistent with their different physiological functions. The expression profiles of the subterranean rhizome provides a better understanding of the biological activities of the underground stem structures that are essentials for perenniality and the storage or remobilization of carbon and nutrient resources.
Comparative transcriptional profiling analysis of olive ripe-fruit pericarp and abscission zone tissues shows expression differences and distinct patterns of transcriptional regulation
Authors: Parra Ruben , Paredes Miguel A , Sanchez-Calle Isabel M , Gomez-Jimenez Maria C 
Published: December 2013

Abstract

Background
In fleshy fruit, abscission of fully ripe fruit is a process intimately linked to the ripening process. In many fruit-tree species, such as olive (Olea europaea L. cv. Picual), there is a coupling of the full ripening and the activation of the abscission-zone (AZ). Although fully ripe fruit have marked physiological differences with respect to their AZs, dissimilarities in gene expression have not been thoroughly investigated. The present study examines the transcriptome of olive fruit and their AZ tissues at the last stage of ripening, monitored using mRNA-Seq.

Results
Roche-454 massive parallel pyrosequencing enabled us to generate 397,457 high-quality EST sequences, among which 199,075 were from ripe-fruit pericarp and 198,382 from AZ tissues. We assembled these sequences into 19,062 contigs, grouped as 17,048 isotigs. Using the read amounts for each annotated isotig (from a total of 15,671), we identified 7,756 transcripts. A comparative analysis of the transcription profiles conducted in ripe-fruit pericarp and AZ evidenced that 4,391 genes were differentially expressed genes (DEGs) in fruit and AZ. Functional categorization of the DEGs revealed that AZ tissue has an apparently higher response to external stimuli than does that of ripe fruit, revealing a higher expression of auxin-signaling genes, as well as lignin catabolic and biosynthetic pathway, aromatic amino acid biosynthetic pathway, isoprenoid biosynthetic pathway, protein amino acid dephosphorylation, amino acid transport, and photosynthesis. By contrast, fruit-enriched transcripts are involved in ATP synthesis coupled proton transport, glycolysis, and cell-wall organization. Furthermore, over 150 transcripts encoding putative transcription-factors (TFs) were identified (37 fruit TFs and 113 AZ TFs), of which we randomly selected eight genes and we confirmed their expression patterns using quantitative RT-PCR.

Conclusion
We generated a set of EST sequences from olive fruit at full ripening, and DEGs between two different olive tissues, ripe fruit and their AZ, were also identified. Regarding the cross-talk between fruit and AZ, using qRT-PCR, we confirmed a set of TF genes that were differentially expressed, revealing profiles of expression that have not previously been reported, this offering a promising beginning for studies on the different transcription regulation in such tissues.
Cathepsin K inhibitors increase distal femoral bone mineral density in rapidly growing rabbits
Authors: Pennypacker Brenda L , Oballa Renata M , Levesque Sonia , Kimmel Donald B , Duong Le T 
Published: December 2013

Abstract

Background
Selective and reversible inhibitors of human Cathepsin K (CatK), including odanacatib (ODN), have been developed as potential therapeutics for the treatment of osteoporosis. Inhibitors of human CatK show significantly less potency for the rodent enzymes compared with that for the human or rabbit enzymes; thus the Schenk model in growing rabbit was developed as a screening assay for the in vivo activity of CatK inhibitors in blocking bone resorption.

Methods
In this study, the efficacy of the selective inhibitors L-833905, L-006235, L-873724, and L-1037536 (ODN) of human CatK in the rapidly growing rabbit ‘Schenk’ model (age seven weeks) was compared to vehicle, using the bisphosphonate, alendronate (ALN), as a positive control, to assess inhibition of bone resorption. An enzyme inhibition assay (EIA) and an in vitro bone resorption assay using rabbit osteoclasts on bovine cortical bone slices were performed to evaluate the potency of these CatK inhibitors. Bone mineral density of the distal femur (DFBMD) was measured after ten days of treatment using ex vivo DXA densitometry.

Results
Results of the EIA using rabbit CatK and the rabbit bone resorption assay showed that three of the four compounds (L-006235, L-873724, and ODN) had similar potencies in the reduction of collagen degradation. L-833905 appeared to be a weaker inhibitor of CatK. Taking into account the respective in vitro potencies and pharmacokinetic profiles via oral administration, the efficacy of these four CatK inhibitors was demonstrated in a dose-related manner in the growing rabbit. Significant increases in DFBMD in animals dosed with the CatK inhibitors compared to vehicle were seen.

Conclusions
Efficacy of the CatK inhibitors in the Schenk rabbit correlated well with that in the in vitro rabbit bone resorption assay and in the ovariectomized rabbit model as previously published. Hence, these studies validated the rabbit Schenk assay as a rapid and reliable in vivo model for prioritizing human CatK inhibitors as potential therapeutic agents.
Antioxidant activity of Coriandrum sativum and protection against DNA damage and cancer cell migration
Authors: Tang Esther LH , Rajarajeswaran Jayakumar , Fung Shin Yee , Kanthimathi MS 
Published: December 2013

AbstractBackgroundCoriandrum sativumis a popular culinary and medicinal herb of the Apiaceae family. Health promoting properties of this herb have been reported in pharmacognostical, phytochemical and pharmacological studies.However, studies onC. sativumhave always focused on the aerial parts of the herb and scientific investigation on the root is limited. The aim of this research was to investigate the antioxidant and anticancer activities ofC. sativumroot, leaf and stem, including its effect on cancer cell migration, and its protection against DNA damage, with special focus on the roots.MethodsPowdered roots, leaves and stems ofC. sativumwere extracted through sequential extraction using hexane, dichloromethane, ethyl acetate, methanol and water. Total phenolic content, FRAP and DPPH radical scavenging activities were measured. Anti-proliferative activitiy on the breast cancer cell line, MCF-7, was assayed using the MTT assay. Activities of the antioxidant enzymes, catalase, superoxide dismutase, glutathione peroxidase, and of the caspases-3, -8 and -9 were assayed on treatment with the extract. Cell cycle progression was analysed using flow cytometry. The scratch motility assay was used to assess inhibition of MCF-7 cell migration. DNA damage in 3 T3-L1 fibroblasts was evaluated by the comet assay. The components in the extract were identified by HPLC and GC-MS.ResultsThe ethyl acetate extract of C. sativumroots showed the highest antiproliferative activity on MCF-7 cells (IC50 = 200.0 ± 2.6 μg/mL) and had the highest phenolic content, FRAP and DPPH scavenging activities among the extracts.C. sativumroot inhibited DNA damage and prevented MCF-7 cell migration induced by H2O2, suggesting its potential in cancer prevention and inhibition of metastasis. The extract exhibited anticancer activity in MCF-7 cells by affecting antioxidant enzymes possibly leading to H2O2accumulation, cell cycle arrest at the G2/M phase and apoptotic cell death by the death receptor and mitochondrial apoptotic pathways.ConclusionsThis study is the first report on the antioxidant and anticancer properties ofC. sativumroot. The herb shows potential in preventing oxidative stress-related diseases and would be useful as supplements used in combination with conventional drugs to enhance the treatment of diseases such as cancer.
Promoting effect of neutrophils on lung tumorigenesis is mediated by CXCR2 and neutrophil elastase
Authors: Gong Lei , Cumpian Amber M , Caetano Mauricio S , Ochoa Cesar E , De la Garza Maria Miguelina , Lapid Daniel J , Mirabolfathinejad Seyedeh Golsar , Dickey Burton F , Zhou Qinghua , Moghaddam Seyed Javad 
Published: December 2013

AbstractBackgroundTumor cells produce various cytokines and chemokines that attract leukocytes. Leukocytes can amplify parenchymal innate immune responses, and have been shown to contribute to tumor promotion. Neutrophils are among the first cells to arrive at sites of inflammation, and the increased number of tumor-associated neutrophils is linked to poorer outcome in patients with lung cancer.ResultsWe have previously shown that COPD-like airway inflammation promotes lung cancer in a K-ras mutant mouse model of lung cancer (CC-LR). This was associated with severe lung neutrophilic influx due to the increased level of neutrophil chemoattractant, KC. To further study the role of neutrophils in lung tumorigenesis, we depleted neutrophils in CC-LR mice using an anti-neutrophil antibody. This resulted in a significant reduction in lung tumor number. We further selectively inhibited the main receptor for neutrophil chemo-attractant KC, CXCR2. Similarly, this resulted in suppression of neutrophil recruitment into the lung of CC-LR mice followed by significant tumor reduction. Neutrophil elastase (NE) is a potent elastolytic enzyme produced by neutrophils at the site of inflammation. We crossed the CC-LR mice with NE knock-out mice, and found that lack of NE significantly inhibits lung cancer development. These were associated with significant reduction in tumor cell proliferation and angiogenesis.ConclusionWe conclude that lung cancer promotion by inflammation is partly mediated by activation of the IL-8/CXCR2 pathway and subsequent recruitment of neutrophils and release of neutrophil elastase. This provides a baseline for future clinical trials using the IL-8/CXCR2 pathway or NE inhibitors in patients with lung cancer.
Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice
Authors: Stokes Jennifer A , Cheung Jonathan , Eddinger Kelly , Corr Maripat , Yaksh Tony L 
Published: December 2013

AbstractBackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in maleTlr2-/-Tlr3-/-,Tlr4-/-,Tlr5-/-,Myd88-/-,Triflps2,Myd88/Triflps2,Tnf-/-, andIfnar1-/-mice. We also examined L5 ligation inTlr4-/-female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferronipost hoctest was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in femaleTlr4-/-mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice.
Risk factors for locoregional recurrence in patients with resected N1 non-small cell lung cancer: a retrospective study to identify patterns of failure and implications for adjuvant radiotherapy
Authors: Fan Chengcheng , Gao Shugeng , Hui Zhouguang , Liang Jun , Lv Jima , Wang Xiaozhen , He Jie , Wang Luhua 
Published: December 2013

Abstract

Background
Meta-analysis of randomized trials has shown that postoperative radiotherapy (PORT) had a detrimental effect on overall survival (OS) in patients with resected N1 non–small cell lung cancer (NSCLC). Conversely, the locoregional recurrence (LR) rate is reported to be high without adjuvant PORT in these patients. We have evaluated the pattern of failure, actuarial risk and risk factors for LR in order to identify the subset of N1 NSCLC patients with the highest risk of LR. These patients could potentially benefit from PORT.

Methods
We conducted a retrospective study on 199 patients with pathologically confirmed T1–3N1M0 NSCLC who underwent surgery. None of the patients had positive surgical margins or received preoperative therapy or PORT. The median follow-up was 53.8 months. Complete mediastinal lymph node (MLN) dissection and examination was defined as ≥3 dissected and examined MLN stations; incomplete MLN dissection or examination (IMD) was defined as <3 dissected or examined MLN stations. The primary end point of this study was freedom from LR (FFLR). Differences between patient groups were compared and risk factors for LR were identified by univariate and multivariate analyses.

Results
LR was identified in 41 (20.6%) patients, distant metastasis (DM) was identified in 79 (39.7%) patients and concurrent LR and DM was identified in 25 (12.6%) patients. The 3- and 5-year OS rates in patients with resected N1 NSCLC were 78.4% and 65.6%, respectively. The corresponding FFLR rates were 80.8% and 77.3%, respectively. Univariate analyses identified that nonsmokers, ≤23 dissected lymph nodes, visceral pleural invasion and lymph node ratio >10% were significantly associated with lower FFLR rates (P < 0.05). Multivariate analyses further confirmed positive lymph nodes at station 10 and IMD as risk factors for LR (P < 0.05). The 5-year LR rate was highest in patients with both these risk factors (48%).

Conclusions
The incidence of LR in patients with surgically resected T1–3N1M0 NSCLC is high. Patients with IMD and positive lymph nodes at station 10 have the highest risk of LR, and may therefore benefit from adjuvant PORT. Further investigations of PORT in this subset of patients are warranted.
Induced pluripotent stem cells from patients with human fibrodysplasia ossificans progressiva show increased mineralization and cartilage formation
Authors: Matsumoto Yoshihisa , Hayashi Yohei , Schlieve Christopher R , Ikeya Makoto , Kim Hannah , Nguyen Trieu D , Sami Salma , Baba Shiro , Barruet Emilie , Nasu Akira , Asaka Isao , Otsuka Takanobu , Yamanaka Shinya , Conklin Bruce R , Toguchida Junya , Hsiao Edward C 
Published: December 2013

AbstractBackgroundAbnormal activation of endochondral bone formation in soft tissues causes significant medical diseases associated with disability and pain. Hyperactive mutations in the bone morphogenetic protein (BMP) type 1 receptor ACVR1 lead to fibrodysplasia ossificans progressiva (FOP), a rare genetic disorder characterized by progressive ossification in soft tissues. However, the specific cellular mechanisms are unclear. In addition, the difficulty obtaining tissue samples from FOP patients and the limitations in mouse models of FOP hamper our ability to dissect the pathogenesis of FOP.MethodsTo address these challenges and develop a “disease model in a dish”, we created human induced pluripotent stem cells (iPS cells) derived from normal and FOP dermal fibroblasts by two separate methods, retroviral integration or integration-free episomal vectors. We tested if the ability to contribute to different steps of endochondral bone formation was different in FOPvs.control iPS cells.ResultsRemarkably, FOP iPS cells showed increased mineralization and enhanced chondrogenesisin vitro. The mineralization phenotypes could be suppressed with a small-molecule inhibitor of BMP signaling, DMH1. Our results indicate that the FOP ACVR1 R206H mutation favors chondrogenesis and increases mineral depositionin vitro.ConclusionsOur findings establish a FOP disease cell model forin vitroexperimentation and provide a proof-of-concept for using human iPS cell models to understand human skeletal disorders.