bluuebunny/crossref_metadata_2025_split huggingface dataset:
Το ερευνητικό σύστημα της Ελλάδας και η εξέλιξη του
Authors: Χατζηπαραδείσης Αστέρης 
Published: June 2016

<p>Ο ρόλος της Έρευνας και Τεχνολογικής Ανάπτυξης (ETΑ) στην οικονομία της γνώσης είναι ιδιαίτερα αναβαθμισμένος. Στη 'στρατηγική της Λισαβόνας', ένας από τους βασικούς στόχους είναι η μεγέθυνση του ερευνητικού συστήματος της Ευρωπαϊκής Ένωσης με αύξηση της δαπάνης για ΕΤΑ από 1,9% του Ακαθάριστου Εγχώριου Προϊόντος το 2000 σε 3% το 2010. Το ερευνητικό σύστημα της Ελλάδας δομήθηκε τις τελευταίες τρεις δεκαετίες μέσα από μία σειρά εθνικών αλλά και κοινοτικών παρεμβάσεων. Στο άρθρο αυτό δίδεται μία περιγραφή των προγραμμάτων που υλοποιήθηκαν και των θεσμικών μέτρων που ελήφθησαν τα τελευταία 30 χρόνια. Διαπιστώνεται δυναμισμός και υψηλή ανταγωνιστικότητα του συστήματος ιδιαίτερα όσον αφορά την έρευνα ακαδημαϊκής κατεύθυνσης. Αντίθετα, ο τομέας των επιχειρήσεων εμφανίζει τη μεγαλύτερη υστέρηση. Συνολικά το μέγεθος του συστήματος είναι ακόμη αρκετά μικρό και, για τον λόγο αυτόν, οι επιπτώσεις του στην οικονομία είναι σημειακές και περιορισμένου βεληνεκούς. Ωστόσο, το ερευνητικό σύστημα αποτελεί ένα από τα ισχυρά συστατικά της ελληνικής οικονομίας και, με κατάλληλες παρεμβάσεις, μπορεί να την ωθήσει σε υψηλότερα επίπεδα ανταγωνιστικότητας και ανάπτυξης. Με δεδομένη την υστέρηση στον τομέα των επιχειρήσεων, εναπόκειται στον ερευνητικό ιστό (ερευνητικά κέντρα, ΑΕΙ, TEI) να αναλάβει τον ρόλο της ατμομηχανής που θα σύρει ολόκληρο το σύστημα προς μία αυτοτροφοδοτούμενη ανάπτυξη. Από την πλευρά της, η πολιτεία οφείλει να δημιουργήσει το κατάλληλο περιβάλλον και τα κατάλληλα εργαλεία τα οποία θα υποστηρίζουν τα ισχυρό σημεία του ερευνητικού συστήματος και θα το προσανατολίσουν προς την παραγωγή όχι μόνο υψηλών ερευνητικών αλλά και σημαντικών οικονομικών αποτελεσμάτων. Η επίτευξη ενός τέτοιου 'ποιοτικού άλματος' δεν είναι εφικτή χωρίς πρόσθετους εθνικούς πόρους οι οποίοι, με ταχεία και ευέλικτη διαχείριση, θα υποστηρίξουν καινοτόμες δράσεις με γρήγορα αποτελέσματα..</p>
Case Report: Kikuchi-Fujimoto disease: a diagnostic and therapeutic dilemma following pretransplant nephrectomy for a 2.35 Kg kidney
Authors: Ganpule Arvind P. , Chabra Jaspreet Singh , Singh Abhishek G. , Tak Gopal R. , Soni Shailesh , Sabnis Ravindra , Desai Mahesh 
Published: June 2016

Kikuchi-Fujimoto disease (KFD) is an extremely rare disease with a worldwide distribution and higher prevalence in Asians. It is a benign and self-limiting disorder, characterized by regional cervical lymphadenopathy accompanied with mild fever and night sweats. Lymph node histopathology is diagnostic and treating physicians should be aware of this entity as it may mimic other systemic diseases like systemic lupus erythematosus, tuberculosis, malignant lymphoma, and more rarely adenocarcinoma. Key features on lymph node biopsy are fragmentation, necrosis and karyorrhexis. Treatment includes symptomatic care, analgesics-antipyretics, corticosteroids and spontaneous recovery occurs in 1 to 4 months. We report a case of adult polycystic kidney disease (ADPKD) with end stage renal disease and episodes of fever and cervical lymphadenopathy. The infectious screen was negative and on extensive workup, the patient was found to have histiocytic-necrotizing lymphadenitis, which clinched the diagnosis of KFD.
Enhancing the Budget Impact Model for Institutional Use: A Tool with Practical Applications for the Hospital Oncology Pharmacy
Authors: Hess Lisa M. , Cinfio Frank N. , Wetmore Stewart , Churchill Collin , Fausel Christopher , Ale-Ali Amine , Gelwicks Steven , Bly Christopher A. , Perk Sinem , Klein Robert W. 
Published: June 2016

Background The cost of cancer care is increasing, and tools are needed to understand the economic impact of new drugs on the hospital pharmacy budget. Objective To develop an interactive budget impact model (BIM) through a collaborative effort of industry, academia, and modeling experts to evaluate the use of a new agent in non-small cell lung cancer (NSCLC); this BIM included an institutional module specific to the needs of practices that purchase medications for use in institutional settings. Methods Treatment regimens, doses, duration of therapy, toxicity, and cost data are from published sources. All input data may be modified to match the local population. Outputs include cost of care, reimbursement, and margin overall and by treatment regimen. Results The base case assumes 20 NSCLC patients progressing after initial therapy (3 receiving ramucirumab+docetaxel, 2 bevacizumab+erlotinib, 3 docetaxel, 6 erlotinib, and 6 pemetrexed), wholesale acquisition cost (WAC) purchase price, and reimbursement at WAC+4.3%. The model estimated the total cost and reimbursement for the institutional oncology pharmacy to be $699,413 and $729,487, respectively, resulting in a margin of $30,075 (difference due to rounding) for the year for regimens utilized in the treatment of NSCLC in the post-progression setting. Results will vary depending on the input data. Conclusions There is an increasing need for institutional pharmacies to plan ahead and anticipate the impact of new drugs on their oncology budgets. This interactive Excel-based institutional BIM may provide evidence-based support for pharmacy decision making.
Comparison of Clevidipine versus Sodium Nitroprusside for the Treatment of Postoperative Hypertension in Cardiac Surgery Patients
Authors: Freiberger Natalie A. , Tellor Katie B. , Stevens Alison M. 
Published: June 2016

Objective To evaluate the efficacy and safety of clevidipine (CLV) versus sodium nitroprusside (SNP) for the treatment of hypertension (HTN) in postoperative cardiac surgery patients at a community hospital. Methods This single-center, retrospective, cohort study included cardiac surgery patients treated with CLV or SNP for postoperative systolic blood pressure (SBP) control. The primary efficacy outcome was defined as the mean number of times the SBP rose above 140 mm Hg. Secondary outcomes included a comparative cost analysis and a safety analysis. Results Forty patients were included in each arm. Patients who received CLV had a higher incidence of SBP readings greater than 140 mm Hg ( p < .05). There were no differences in safety outcomes, number of patients who received as-needed (PRN) antihypertensives, or mean number of PRN antihypertensives required. There were differences in infusion duration (22.4 hours CLV vs 15.6 hours SNP; p = .035), number of infusions dispensed (2.8 CLV vs 1.3 SNP; p = .001), and length of hospital stay (12.33 days CLV vs 7.65 days SNP; p = .013). However, CLV was less expensive based on the AWP cost at the time of review. Conclusions Although a difference in blood pressure control was seen between CLV and SNP, the safety profiles were similar between the 2 drugs. In addition, CLV remained less expensive than SNP for postoperative BP control.
AKT isoforms modulate Th1‐like Treg generation and function in human autoimmune disease
Authors: Kitz Alexandra , de Marcken Marine , Gautron Anne‐Sophie , Mitrovic Mitja , Hafler David A , Dominguez‐Villar Margarita 
Published: June 2016

AbstractFoxp3+ regulatory T cells (Tregs) exhibit plasticity, which dictates their function. Secretion of the inflammatory cytokine IFNγ, together with the acquisition of a T helper 1 (Th1)‐like effector phenotype as observed in cancer, infection, and autoimmune diseases, is associated with loss of Treg suppressor function through an unknown mechanism. Here, we describe the signaling events driving the generation of human Th1‐Tregs. Using a genome‐wide gene expression approach and pathway analysis, we identify the PI3K/AKT/Foxo1/3 signaling cascade as the major pathway involved in IFNγ secretion by human Tregs. Furthermore, we describe the opposing roles of AKT isoforms in Th1‐Treg generation ex vivo. Finally, we employ multiple sclerosis as an in vivo model with increased but functionally defective Th1‐Tregs. We show that the PI3K/AKT/Foxo1/3 pathway is activated in ex vivo‐isolated Tregs from untreated relapsing–remitting MS patients and that blockade of the pathway inhibits IFNγ secretion and restores the immune suppressive function of Tregs. These data define a fundamental pathway regulating the function of human Tregs and suggest a novel treatment paradigm for autoimmune diseases.
Genomic Signatures of Experimental Adaptation to Antimicrobial Peptides in Staphylococcus aureus
Authors: Johnston Paul R , Dobson Adam J , Rolff Jens 
Published: June 2016

Abstract
The evolution of resistance against antimicrobial peptides has long been considered unlikely due to their mechanism of action, yet experimental selection with antimicrobial peptides (AMPs) results in rapid evolution of resistance in several species of bacteria. Although numerous studies have utilized mutant screens to identify loci that determine AMP susceptibility, there is a dearth of data concerning the genomic changes that accompany experimental evolution of AMP resistance. Using genome resequencing, we analyzed the mutations that arose during experimental evolution of resistance to the cationic AMPs iseganan, melittin, and pexiganan, as well as to a combination of melittin and pexiganan, or to the aminoglycoside antibiotic streptomycin. Analysis of 17 independently replicated Staphylococcus aureus selection lines, including unselected controls, showed that each AMP selected for mutations at distinct loci. We identify mutations in genes involved in the synthesis and maintenance of the cell envelope. These include genes previously identified from mutant screens for AMP resistance, and genes involved in the response to AMPs and cell-wall-active antibiotics. Furthermore, transposon insertion mutants were used to verify that a number of the identified genes are directly involved in determining AMP susceptibility. Strains selected for AMP resistance under controlled experimental evolution displayed consistent AMP-specific mutations in genes that determine AMP susceptibility. This suggests that different routes to evolve resistance are favored within a controlled genetic background.
The Sorghum Gene for Leaf Color Changes upon Wounding (P) Encodes a Flavanone 4-Reductase in the 3-Deoxyanthocyanidin Biosynthesis Pathway
Authors: Kawahigashi Hiroyuki , Kasuga Shigemitsu , Sawada Yuji , Yonemaru Jun-ichi , Ando Tsuyu , Kanamori Hiroyuki , Wu Jianzhong , Mizuno Hiroshi , Momma Mitsuru , Fujimoto Zui , Hirai Masami Yokota , Matsumoto Takashi 
Published: June 2016

Abstract
Upon wounding or pathogen invasion, leaves of sorghum [Sorghum bicolor (L.) Moench] plants with the P gene turn purple, whereas leaves with the recessive allele turn brown or tan. This purple phenotype is determined by the production of two 3-deoxyanthocyanidins, apigeninidin and luteolinidin, which are not produced by the tan-phenotype plants. Using map-based cloning in progeny from a cross between purple Nakei-MS3B (PP) and tan Greenleaf (pp) cultivars, we isolated this gene, which was located in a 27-kb genomic region around the 58.1 Mb position on chromosome 6. Four candidate genes identified in this region were similar to the maize leucoanthocyanidin reductase gene. None of them was expressed before wounding, and only the Sb06g029550 gene was induced in both cultivars after wounding. The Sb06g029550 protein was detected in Nakei-MS3B, but only slightly in Greenleaf, in which it may be unstable because of a Cys252Tyr substitution. A recombinant Sb06g029550 protein had a specific flavanone 4-reductase activity, and converted flavanones (naringenin or eriodictyol) to flavan-4-ols (apiforol or luteoforol) in vitro. Our data indicate that the Sb06g029550 gene is involved in the 3-deoxyanthocyanidin synthesis pathway.
The HIST1 Locus Escapes Reprogramming in Cloned Bovine Embryos
Authors: Min Byungkuk , Cho Sunwha , Park Jung Sun , Jeon Kyuheum , Kang Yong-Kook 
Published: June 2016

Abstract
Epigenetic reprogramming is necessary in somatic cell nuclear transfer (SCNT) embryos in order to erase the differentiation-associated epigenetic marks of donor cells. However, such epigenetic memories often persist throughout the course of clonal development, thus decreasing cloning efficiency. Here, we explored reprogramming-refractory regions in bovine SCNT blastocyst transcriptomes. We observed that histone genes residing in the 1.5 Mb spanning the cow HIST1 cluster were coordinately downregulated in SCNT blastocysts. In contrast, both the nonhistone genes of this cluster, and histone genes elsewhere remained unaffected. This indicated that the downregulation was specific to HIST1 histone genes. We found that, after trichostatin A treatment, HIST1 histone genes were derepressed, and DNA methylation at their promoters was decreased to the level of in vitro fertilization embryos. Therefore, our results indicate that the reduced expression of HIST1 histone genes is a consequence of poor epigenetic reprogramming in SCNT blastocysts.
Several Critical Cell Types, Tissues, and Pathways Are Implicated in Genome-Wide Association Studies for Systemic Lupus Erythematosus
Authors: Liu Lu , Yin Xianyong , Wen Leilei , Yang Chao , Sheng Yujun , Lin Yan , Zhu Zhengwei , Shen Changbing , Shi Yinjuan , Zheng Yajie , Yang Sen , Zhang Xuejun , Cui Yong 
Published: June 2016

Abstract
We aimed to elucidate the cell types, tissues, and pathways influenced by common variants in systemic lupus erythematosus (SLE). We applied a nonparameter enrichment statistical approach, termed SNPsea, in 181 single nucleotide polymorphisms (SNPs) that have been identified to be associated with the risk of SLE through genome-wide association studies (GWAS) in Eastern Asian and Caucasian populations, to manipulate the critical cell types, tissues, and pathways. In the two most significant cells’ findings (B lymphocytes and CD14+ monocytes), we subjected the GWAS association evidence in the Han Chinese population to an enrichment test of expression quantitative trait locus (QTL) sites and DNase I hypersensitivity, respectively. In both Eastern Asian and Caucasian populations, we observed that the expression level of SLE GWAS implicated genes was significantly elevated in xeroderma pigentosum B cells (P ≤ 1.00 × 10−6), CD14+ monocytes (P ≤ 2.74 × 10−4) and CD19+ B cells (P ≤ 2.00 × 10−6), and plasmacytoid dendritic cells (pDCs) (P ≤ 9.00 × 10−6). We revealed that the SLE GWAS-associated variants were more likely to reside in expression QTL in B lymphocytes (q1/q0 = 2.15, P = 1.23 × 10−44) and DNase I hypersensitivity sites (DHSs) in CD14+ monocytes (q1/q0 = 1.41, P = 0.08). We observed the common variants affected the risk of SLE mostly through by regulating multiple immune system processes and immune response signaling. This study sheds light on several immune cells and responses, as well as the regulatory effect of common variants in the pathogenesis of SLE.
Interconnections Between RNA-Processing Pathways Revealed by a Sequencing-Based Genetic Screen for Pre-mRNA Splicing Mutants in Fission Yeast
Authors: Larson Amy , Fair Benjamin Jung , Pleiss Jeffrey A 
Published: June 2016

Abstract
Pre-mRNA splicing is an essential component of eukaryotic gene expression and is highly conserved from unicellular yeasts to humans. Here, we present the development and implementation of a sequencing-based reverse genetic screen designed to identify nonessential genes that impact pre-mRNA splicing in the fission yeast Schizosaccharomyces pombe, an organism that shares many of the complex features of splicing in higher eukaryotes. Using a custom-designed barcoding scheme, we simultaneously queried ∼3000 mutant strains for their impact on the splicing efficiency of two endogenous pre-mRNAs. A total of 61 nonessential genes were identified whose deletions resulted in defects in pre-mRNA splicing; enriched among these were factors encoding known or predicted components of the spliceosome. Included among the candidates identified here are genes with well-characterized roles in other RNA-processing pathways, including heterochromatic silencing and 3ʹ end processing. Splicing-sensitive microarrays confirm broad splicing defects for many of these factors, revealing novel functional connections between these pathways.
Multiple Targets on the Gln3 Transcription Activator Are Cumulatively Required for Control of Its Cytoplasmic Sequestration
Authors: Rai Rajendra , Tate Jennifer J , Cooper Terrance G 
Published: June 2016

Abstract
A remarkable characteristic of nutritional homeostatic mechanisms is the breadth of metabolite concentrations to which they respond, and the resolution of those responses; adequate but rarely excessive. Two general ways of achieving such exquisite control are known: stoichiometric mechanisms where increasing metabolite concentrations elicit proportionally increasing responses, and the actions of multiple independent metabolic signals that cumulatively generate appropriately measured responses. Intracellular localization of the nitrogen-responsive transcription activator, Gln3, responds to four distinct nitrogen environments: nitrogen limitation or short-term starvation, i.e., nitrogen catabolite repression (NCR), long-term starvation, glutamine starvation, and rapamycin inhibition of mTorC1. We have previously identified unique sites in Gln3 required for rapamycin-responsiveness, and Gln3-mTor1 interaction. Alteration of the latter results in loss of about 50% of cytoplasmic Gln3 sequestration. However, except for the Ure2-binding domain, no evidence exists for a Gln3 site responsible for the remaining cytoplasmic Gln3-Myc13 sequestration in nitrogen excess. Here, we identify a serine/threonine-rich (Gln3477–493) region required for effective cytoplasmic Gln3-Myc13 sequestration in excess nitrogen. Substitutions of alanine but not aspartate for serines in this peptide partially abolish cytoplasmic Gln3 sequestration. Importantly, these alterations have no effect on the responses of Gln3-Myc13 to rapamycin, methionine sulfoximine, or limiting nitrogen. However, cytoplasmic Gln3-Myc13 sequestration is additively, and almost completely, abolished when mutations in the Gln3-Tor1 interaction site are combined with those in Gln3477–493 cytoplasmic sequestration site. These findings clearly demonstrate that multiple individual regulatory pathways cumulatively control cytoplasmic Gln3 sequestration.
Genetic Background, Maternal Age, and Interaction Effects Mediate Rates of Crossing Over inDrosophila melanogasterFemales
Authors: Hunter Chad M , Robinson Matthew C , Aylor David L , Singh Nadia D 
Published: June 2016

AbstractMeiotic recombination is a genetic process that is critical for proper chromosome segregation in many organisms. Despite being fundamental for organismal fitness, rates of crossing over vary greatly between taxa. Both genetic and environmental factors contribute to phenotypic variation in crossover frequency, as do genotype–environment interactions. Here, we test the hypothesis that maternal age influences rates of crossing over in a genotypic-specific manner. Using classical genetic techniques, we estimated rates of crossing over for individual Drosophila melanogaster females from five strains over their lifetime from a single mating event. We find that both age and genetic background significantly contribute to observed variation in recombination frequency, as do genotype–age interactions. We further find differences in the effect of age on recombination frequency in the two genomic regions surveyed. Our results highlight the complexity of recombination rate variation and reveal a new role of genotype by maternal age interactions in mediating recombination rate.
Sdt97: A Point Mutation in the 5′ Untranslated Region Confers Semidwarfism in Rice
Authors: Tong Jiping , Han Zhengshu , Han Aonan , Liu Xuejun , Zhang Shiyong , Fu Binying , Hu Jun , Su Jingping , Li Shaoqing , Wang Shengjun , Zhu Yingguo 
Published: June 2016

Abstract
Semidwarfism is an important agronomic trait in rice breeding programs. The semidwarf mutant gene Sdt97 was previously described. However, the molecular mechanism underlying the mutant is yet to be elucidated. In this study, we identified the mutant gene by a map-based cloning method. Using a residual heterozygous line (RHL) population, Sdt97 was mapped to the long arm of chromosome 6 in the interval of nearly 60 kb between STS marker N6 and SNP marker N16 within the PAC clone P0453H04. Sequencing of the candidate genes in the target region revealed that a base transversion from G to C occurred in the 5′ untranslated region of Sdt97. qRT-PCR results confirmed that the transversion induced an obvious change in the expression pattern of Sdt97 at different growth and developmental stages. Plants transgenic for Sdt97 resulted in the restoration of semidwarfism of the mutant phenotype, or displayed a greater dwarf phenotype than the mutant. Our results indicate that a point mutation in the 5′ untranslated region of Sdt97 confers semidwarfism in rice. Functional analysis of Sdt97 will open a new field of study for rice semidwarfism, and also expand our knowledge of the molecular mechanism of semidwarfism in rice.
Genome Sequence and Analysis of a Stress-Tolerant, Wild-Derived Strain ofSaccharomyces cerevisiaeUsed in Biofuels Research
Authors: McIlwain Sean J , Peris David , Sardi Maria , Moskvin Oleg V , Zhan Fujie , Myers Kevin S , Riley Nicholas M , Buzzell Alyssa , Parreiras Lucas S , Ong Irene M , Landick Robert , Coon Joshua J , Gasch Audrey P , Sato Trey K , Hittinger Chris Todd 
Published: June 2016

AbstractThe genome sequences of more than 100 strains of the yeast Saccharomyces cerevisiae have been published. Unfortunately, most of these genome assemblies contain dozens to hundreds of gaps at repetitive sequences, including transposable elements, tRNAs, and subtelomeric regions, which is where novel genes generally reside. Relatively few strains have been chosen for genome sequencing based on their biofuel production potential, leaving an additional knowledge gap. Here, we describe the nearly complete genome sequence of GLBRCY22-3 (Y22-3), a strain of S. cerevisiae derived from the stress-tolerant wild strain NRRL YB-210 and subsequently engineered for xylose metabolism. After benchmarking several genome assembly approaches, we developed a pipeline to integrate Pacific Biosciences (PacBio) and Illumina sequencing data and achieved one of the highest quality genome assemblies for any S. cerevisiae strain. Specifically, the contig N50 is 693 kbp, and the sequences of most chromosomes, the mitochondrial genome, and the 2-micron plasmid are complete. Our annotation predicts 92 genes that are not present in the reference genome of the laboratory strain S288c, over 70% of which were expressed. We predicted functions for 43 of these genes, 28 of which were previously uncharacterized and unnamed. Remarkably, many of these genes are predicted to be involved in stress tolerance and carbon metabolism and are shared with a Brazilian bioethanol production strain, even though the strains differ dramatically at most genetic loci. The Y22-3 genome sequence provides an exceptionally high-quality resource for basic and applied research in bioenergy and genetics.