bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepcidin links gluco-toxicity to pancreatic beta cell dysfunction by inhibiting Pdx-1 expression
Authors: Mao Xuhua , Chen Hucheng , Tang Junmin , Wang Liangliang , Shu Tingting 
Published: February 2017

Objective
Gluco-toxicity is a term used to convey the detrimental effect of hyperglycemia on β-cell function through impaired insulin synthesis. Although it is known that the expression and activity of several key insulin transcription regulators is inhibited, other molecular mechanisms that mediate gluco-toxicity are poorly defined. Our objective was to explore the role of hepcidin in β-cell gluco-toxicity.

Design
We first confirmed that high glucose levels inhibited hepcidin expression in the mouse insulinoma cell line, MIN6. The downregulation of hepcidin decreased Pdx-1 expression, which reduced insulin synthesis.

Methods
MIN6 cells were exposed to high glucose concentrations (33.3 mmol/L). Glucose-stimulated insulin secretion (GSIS) and serum hepcidin levels were measured by ELISA. The mRNA levels of insulin1, insulin2, Pdx-1 and hepcidin were measured by real-time polymerase chain reaction. Western blot analysis was used to detect the changes in PDX-1 expression. Transient overexpression with hepcidin was used to reverse the downregulation of Pdx-1 and insulin synthesis induced by gluco-toxicity.

Results
Exposure of MIN6 cells to high glucose significantly decreased GSIS and inhibited insulin synthesis as well as Pdx-1 transcriptional activity and expression at both the mRNA and protein levels. High glucose also decreased hepcidin expression and secretion. Hepcidin overexpression in MIN6 cells partially reversed the gluco-toxicity-induced downregulation of Pdx-1 and insulin expression and improved GSIS. The restoration of insulin synthesis by transfection of a hepcidin overexpression plasmid confirmed the role of hepcidin in mediating the gluco-toxic inhibition of insulin synthesis.

Conclusions
Our observations suggest that hepcidin is associated with gluco-toxicity-reduced pancreatic β-cell insulin synthesis in type 2 diabetes by inhibiting Pdx-1 expression.
Risk factors for post-thyroidectomy haemorrhage: a meta-analysis
Authors: Liu Jinhao , Sun Wei , Dong Wenwu , Wang Zhihong , Zhang Ping , Zhang Ting , Zhang Hao 
Published: February 2017

BackgroundPost-thyroidectomy haemorrhage is a rare but potentially life-threatening and unpredictable complication of thyroid surgery. In this study, we analysed the potential risk factors for the occurrence of post-thyroidectomy haemorrhage.MethodsThe PubMed and SCIE databases were comprehensively searched for studies published before June 30, 2016. Studies on patients who underwent an open thyroidectomy with or without neck dissection were included, and RevMan 5.3 software was used to analyse the data.ResultsTwenty-five studies and 424 563 patients were included in this meta-analysis, and post-thyroidectomy haemorrhage occurred in 6277 patients (incidence rate = 1.48%). The following variables were associated with an increased risk of post-thyroidectomy haemorrhage: older age (MD = 4.30, 95% CI = 3.09–5.52,P < 0.00001), male sex (OR = 1.73, 95% CI = 1.54–1.94,P < 0.00001), Graves’ disease (OR = 1.76, 95% CI = 1.44–2.15,P < 0.00001), antithrombotic agents use (OR = 1.96, 95% CI 1.55–2.49,P < 0.00001), bilateral operation (OR = 1.71, 95% CI = 1.50–1.96,P < 0.00001), neck dissection (OR = 1.53, 95% CI = 1.11–2.11,P = 0.01) and previous thyroid surgery (OR = 1.62, 95% CI = 1.12–2.34,P = 0.01). Malignant tumours (OR = 1.07, 95% CI = 0.89–1.28,P = 0.46) and drainage device use (OR = 1.27, 95% CI = 0.74–2.18,P = 0.4) were not associated with post-thyroidectomy haemorrhage.ConclusionOur systematic review identified a number of risk factors for post-thyroidectomy haemorrhage, including older age, male sex, Graves’ disease, antithrombotic agents use, bilateral operation, neck dissection and previous thyroid surgery. Early control of modifiable risk factors could improve patient outcomes and satisfaction.
The GIP/GIPR axis is functionally linked to GH-secretion increase in a significant proportion of gsp− somatotropinomas
Authors: Regazzo D , Losa M , Albiger N M , Terreni M R , Vazza G , Ceccato F , Emanuelli E , Denaro L , Scaroni C , Occhi G 
Published: February 2017

ObjectiveGlucose-dependent insulinotropic polypeptide receptor (GIPR) overexpression has been recently described in a proportion ofgsp−somatotropinomas and suggested to be associated with the paradoxical increase of GH (GH-PI) during an oral glucose load.Design and methodsThis study was aimed at linking the GIP/GIPR pathway to GH secretion in 25 somatotropinomas-derived primary cultures and correlating molecular with clinical features in acromegalic patients. Given the impairment of the GIP/GIPR axis in acromegaly, an additional aim was to assess the effect of GH/IGF-1 stimulation on GIP expression in the enteroendocrine cell line STC-1.ResultsNearly 80% ofGIPR-expressing somatotropinomas, all of them negative forgspmutations, show increased GH secretion upon GIP stimulation, higher sensitivity to Forskolin but not to somatostatin analogs. Besides increased frequency of GH-PI,GIPRoverexpression does not appear to affect acromegalic patients’ clinical features. In STC-1 cells transfected with GIP promoter-driven luciferase vector, IGF-1 but not GH induced dose-dependent increase in luciferase activity.ConclusionsWe demonstrate thatGIPRmediates the GH-PI in a significant proportion ofgsp−acromegalic patients. In these cases, the stimulatory effect of IGF-1 on GIP promoter support the hypothesis of a functional GH/IGF-1/GIP axis. Further studies based on larger cohorts and the development of a stable transgenic model with inducible GIPR overexpression targeted to pituitary somatotroph lineage will be mandatory to establish the real role of GIPR in the pathogenesis of somatotropinomas.
Cushing’s syndrome in children and adolescents: a Danish nationwide population-based cohort study
Authors: Holst Johanne Marie , Horváth-Puhó Erzsébet , Jensen Rikke Beck , Rix Mariane , Kristensen Kurt , Hertel Niels Thomas , Dekkers Olaf M , Sørensen Henrik Toft , Juul Anders , Jørgensen Jens Otto L 
Published: February 2017

Objective
Cushing’s syndrome (CS) affects all age groups, but epidemiologic data in young patients are very limited. We therefore examined the incidence, prevalence and hospital morbidity of CS in children and adolescents.

Design
In a nationwide cohort study, we included all Danish citizens aged 0–20 years from 1977 to 2012. Data were obtained from the Danish National Patient Registry using the International Classification of Diseases (ICD) codes and the Danish Civil Registration System. The diagnosis and treatment were validated by means of individual patient charts. Incidence rate of CS patients aged 0–20 years at diagnosis were computed (standardized to the age and sex distribution of the Danish population). The patients were followed for a maximum of 36 years. Standardized incidence ratios (SIRs) of different hospital-recorded outcomes based on the ICD codes in patients with CS compared to the general population were assessed.

Results
We identified a total of 40 pediatric patients with CS, yielding an annual incidence of 0.89 cases/106 population (95% confidence interval (CI) = 0.63–1.16). The median age at the time of diagnosis was 13.8 years (interquartile range: 10.5–18.2 years), 58% were female and 70% had adrenocorticotropic hormone-producing pituitary adenomas. During follow-up, CS patients (excluding three malignant cases) were at increased risk of being diagnosed with infections (SIR: 3.24, 95% CI: 1.05–7.54) and infertility (SIR: 4.56, 95% CI: 1.48–10.63). The three patients with an adrenocortical carcinoma died shortly after diagnosis, but mortality was not increased in the remaining patients.

Conclusions
CS is rare in the pediatric population. The risk of morbidity related to infections and infertility is elevated and merits further attention.
The IGF system in patients with type 2 diabetes: associations with markers of cardiovascular target organ damage
Authors: Hjortebjerg Rikke , Laugesen Esben , Høyem Pernille , Oxvig Claus , Stausbøl-Grøn Brian , Knudsen Søren T , Kim Won Y , Poulsen Per L , Hansen Troels K , Bjerre Mette , Frystyk Jan 
Published: February 2017

Objective
Perturbations in the insulin-like growth factor (IGF) system may contribute to the accelerated cardiovascular disease (CVD) that occurs in patients with type 2 diabetes (T2D). However, it remains unknown whether the IGF system is also involved in the development of early, subclinical CVD. We characterised the IGF system in T2D patients and matched controls and examined the associations with markers of subclinical target organ damage.

Methods
The study included 99 patients with recently diagnosed T2D and 99 age- and sex-matched controls. IGF-1 and IGFBP-1 to -4 were measured by immunoassays, as were pregnancy-associated plasma protein-A (PAPP-A) and the PAPP-A-generated N-terminal (NT) and C-terminal (CT) IGFBP-4 fragments, which are novel CVD risk markers. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (PWV). Cerebral white matter lesions (WMLs) and carotid artery remodelling were determined by MRI.

Results
After multivariate adjustments, patients with T2D had lower concentrations of IGFBP-2, IGFBP-4, NT- and CT-IGFBP-4, when compared with controls. IGFBP-2 was inversely correlated to PWV in all subjects in multivariate analysis (P < 0.05), and IGFBP-3 was inversely associated with severity of WMLs (P < 0.05). The NT-IGFBP-4 fragment was associated with the degree of carotid artery remodelling among all subjects (regression coefficient (95% CI): 2.95 (0.70, 5.16), P = 0.011). Levels of NT- and CT-IGFBP-4 were reduced in T2D patients receiving metformin compared to those in controls and patients not receiving metformin.

Conclusions
Even in recently diagnosed and well-controlled T2D patients, IGF protein levels are altered and associated with CVD risk factors.
Comparative Analysis Highlights Variable Genome Content of Wheat Rusts and Divergence of the Mating Loci
Authors: Cuomo Christina A , Bakkeren Guus , Khalil Hala Badr , Panwar Vinay , Joly David , Linning Rob , Sakthikumar Sharadha , Song Xiao , Adiconis Xian , Fan Lin , Goldberg Jonathan M , Levin Joshua Z , Young Sarah , Zeng Qiandong , Anikster Yehoshua , Bruce Myron , Wang Meinan , Yin Chuntao , McCallum Brent , Szabo Les J , Hulbert Scot , Chen Xianming , Fellers John P 
Published: February 2017

AbstractThree members of the Puccinia genus, Pucciniatriticina (Pt), P. striiformis f.sp. tritici (Pst), and P. graminis f.sp. tritici (Pgt), cause the most common and often most significant foliar diseases of wheat. While similar in biology and life cycle, each species is uniquely adapted and specialized. The genomes of Pt and Pst were sequenced and compared to that of Pgt to identify common and distinguishing gene content, to determine gene variation among wheat rust pathogens, other rust fungi, and basidiomycetes, and to identify genes of significance for infection. Pt had the largest genome of the three, estimated at 135 Mb with expansion due to mobile elements and repeats encompassing 50.9% of contig bases; in comparison, repeats occupy 31.5% for Pst and 36.5% for Pgt. We find all three genomes are highly heterozygous, with Pst [5.97 single nucleotide polymorphisms (SNPs)/kb] nearly twice the level detected in Pt (2.57 SNPs/kb) and that previously reported for Pgt. Of 1358 predicted effectors in Pt, 784 were found expressed across diverse life cycle stages including the sexual stage. Comparison to related fungi highlighted the expansion of gene families involved in transcriptional regulation and nucleotide binding, protein modification, and carbohydrate degradation enzymes. Two allelic homeodomain pairs, HD1 and HD2, were identified in each dikaryotic Puccinia species along with three pheromone receptor (STE3) mating-type genes, two of which are likely representing allelic specificities. The HD proteins were active in a heterologous Ustilago maydis mating assay and host-induced gene silencing (HIGS) of the HD and STE3 alleles reduced wheat host infection.
Screening and Analysis of Janelia FlyLight Project Enhancer-Gal4 Strains Identifies Multiple Gene Enhancers Active During Hematopoiesis in Normal and Wasp-ChallengedDrosophilaLarvae
Authors: Tokusumi Tsuyoshi , Tokusumi Yumiko , Brahier Mark S , Lam Victoria , Stoller-Conrad Jessica R , Kroeger Paul T , Schulz Robert A 
Published: February 2017

AbstractA GFP expression screen has been conducted on &gt;1000 Janelia FlyLight Project enhancer-Gal4 lines to identify transcriptional enhancers active in the larval hematopoietic system. A total of 190 enhancers associated with 87 distinct genes showed activity in cells of the third instar larval lymph gland and hemolymph. That is, gene enhancers were active in cells of the lymph gland posterior signaling center (PSC), medullary zone (MZ), and/or cortical zone (CZ), while certain of the transcriptional control regions were active in circulating hemocytes. Phenotypic analyses were undertaken on 81 of these hematopoietic-expressed genes, with nine genes characterized in detail as to gain- and loss-of-function phenotypes in larval hematopoietic tissues and blood cells. These studies demonstrated the functional requirement of the cut gene for proper PSC niche formation, the hairy, Btk29A, and E2F1 genes for blood cell progenitor production in the MZ domain, and the longitudinals lacking, dFOXO, kayak, cap-n-collar, and delilah genes for lamellocyte induction and/or differentiation in response to parasitic wasp challenge and infestation of larvae. Together, these findings contribute substantial information to our knowledge of genes expressed during the larval stage of Drosophila hematopoiesis and newly identify multiple genes required for this developmental process.
A High Copy Suppressor Screen for Autophagy Defects inSaccharomyces arl1Δ andypt6Δ Strains
Authors: Yang Shu , Rosenwald Anne 
Published: February 2017

AbstractIn Saccharomyces cerevisiae, Arl1 and Ypt6, two small GTP-binding proteins that regulate membrane traffic in the secretory and endocytic pathways, are also necessary for autophagy. To gain information about potential partners of Arl1 and Ypt6 specifically in autophagy, we carried out a high copy number suppressor screen to identify genes that when overexpressed suppress the rapamycin sensitivity phenotype of arl1Δ and ypt6Δ strains at 37°. From the screen results, we selected COG4, SNX4, TAX4, IVY1, PEP3, SLT2, and ATG5, either membrane traffic or autophagy regulators, to further test whether they can suppress the specific autophagy defects of arl1Δ and ypt6Δ strains. As a result, we identified COG4, SNX4, and TAX4 to be specific suppressors for the arl1Δ strain, and IVY1 and ATG5 for the ypt6Δ strain. Through this screen, we were able to confirm several membrane traffic and autophagy regulators that have novel relationships with Arl1 and Ypt6 during autophagy.
Exon-Enriched Libraries Reveal Large Genic Differences Between Aedes aegypti from Senegal, West Africa, and Populations Outside Africa
Authors: Dickson Laura B , Campbell Corey L , Juneja Punita , Jiggins Francis M , Sylla Massamba , Black William C 
Published: February 2017

Abstract
Aedes aegypti is one of the most studied mosquito species, and the principal vector of several arboviruses pathogenic to humans. Recently failure to oviposit, low fecundity, and poor egg-to-adult survival were observed when Ae. aegypti from Senegal (SenAae) West Africa were crossed with Ae. aegypti (Aaa) from outside of Africa, and in SenAae intercrosses. Fluorescent in situ hybridization analyses indicated rearrangements on chromosome 1, and pericentric inversions on chromosomes 2 and 3. Herein, high throughput sequencing (HTS) of exon-enriched libraries was used to compare chromosome-wide genetic diversity among Aaa collections from rural Thailand and Mexico, a sylvatic collection from southeastern Senegal (PK10), and an urban collection from western Senegal (Kaolack). Sex-specific polymorphisms were analyzed in Thailand and PK10 to assess genetic differences between sexes. Expected heterozygosity was greatest in SenAae. FST distributions of 15,735 genes among all six pairwise comparisons of the four collections indicated that Mexican and Thailand collections are genetically similar, while FST distributions between PK10 and Kaolack were distinct. All four comparisons of SenAae with Aaa indicated extreme differentiation. FST was uniform between sexes across all chromosomes in Thailand, but were different, especially on the sex autosome 1, in PK10. These patterns correlate with the reproductive isolation noted earlier. We hypothesize that cryptic Ae. aegypti taxa may exist in West Africa, and the large genic differences between Aaa and SenAae detected in the present study have accumulated over a long period following the evolution of chromosome rearrangements in allopatric populations that subsequently cause reproductive isolation when these populations became sympatric.
The Impact of Open Pollination on the Structural Evolutionary Dynamics, Meiotic Behavior, and Fertility of Resynthesized AllotetraploidBrassica napusL.
Authors: Rousseau-Gueutin Mathieu , Morice Jérôme , Coriton Olivier , Huteau Virginie , Trotoux Gwenn , Nègre Sylvie , Falentin Cyril , Deniot Gwennaëlle , Gilet Marie , Eber Frédérique , Pelé Alexandre , Vautrin Sonia , Fourment Joëlle , Lodé Maryse , Bergès Hélène , Chèvre Anne-Marie 
Published: February 2017

AbstractAllopolyploidy, which results from the merger and duplication of two divergent genomes, has played a major role in the evolution and diversification of flowering plants. The genomic changes that occur in resynthesized or natural neopolyploids have been extensively studied, but little is known about the effects of the reproductive mode in the initial generations that may precede its successful establishment. To truly reflect the early generations of a nascent polyploid, two resynthesized allotetraploid Brassica napus populations were obtained for the first time by open pollination. In these populations, we detected a much lower level of aneuploidy (third generation) compared with those previously published populations obtained by controlled successive selfing. We specifically studied 33 resynthesized B. napus individuals from our two open pollinated populations, and showed that meiosis was affected in both populations. Their genomes were deeply shuffled after allopolyploidization: up to 8.5 and 3.5% of the C and A subgenomes were deleted in only two generations. The identified deletions occurred mainly at the distal part of the chromosome, and to a significantly greater extent on the C rather than the A subgenome. Using Fluorescent In Situ Hybridization (BAC-FISH), we demonstrated that four of these deletions corresponded to fixed translocations (via homeologous exchanges). We were able to evaluate the size of the structural variations and their impact on the whole genome size, gene content, and allelic diversity. In addition, the evolution of fertility was assessed, to better understand the difficulty encountered by novel polyploid individuals before the putative formation of a novel stable species.
Genome Report: Identification and Validation of Antigenic Proteins from Pajaroellobacter abortibovis Using De Novo Genome Sequence Assembly and Reverse Vaccinology
Authors: Welly Bryan T , Miller Michael R , Stott Jeffrey L , Blanchard Myra T , Islas-Trejo Alma D , O’Rourke Sean M , Young Amy E , Medrano Juan F , Van Eenennaam Alison L 
Published: February 2017

Abstract
Epizootic bovine abortion (EBA), or “foothill abortion,” is the leading cause of beef cattle abortion in California and has also been reported in Nevada and Oregon. In the 1970s, the soft-shelled tick Ornithodoros coriaceus, or “pajaroello tick,” was confirmed as the disease-transmitting vector. In 2005, a novel Deltaproteobacterium was discovered as the etiologic agent of EBA (aoEBA), recently named Pajaroellobacter abortibovis. This organism cannot be grown in culture using traditional microbiological techniques; it can only be grown in experimentally-infected severe combined immunodeficient (SCID) mice. The objectives of this study were to perform a de novo genome assembly for P. abortibovis and identify and validate potential antigenic proteins as candidates for future recombinant vaccine development. DNA and RNA were extracted from spleen tissue collected from experimentally-infected SCID mice following exposure to P. abortibovis. This combination of mouse and bacterial DNA was sequenced and aligned to the mouse genome. Mouse sequences were subtracted from the sequence pool and the remaining sequences were de novo assembled at 50x coverage into a 1.82 Mbp complete closed circular Deltaproteobacterial genome containing 2250 putative protein-coding sequences. Phylogenetic analysis of P. abortibovis predicts that this bacterium is most closely related to the organisms of the order Myxococcales, referred to as Myxobacteria. In silico prediction of vaccine candidates was performed using a reverse vaccinology approach resulting in the identification and ranking of the top 10 candidate proteins that are likely to be antigenic. Immunologic testing of these candidate proteins confirmed antigenicity of seven of the nine expressed protein candidates using serum from P. abortibovis immunized mice.
Expression Patterns of Atlantic Sturgeon (Acipenser oxyrinchus) During Embryonic Development
Authors: Kaitetzidou Elisavet , Ludwig Arne , Gessner Jörn , Sarropoulou Elena 
Published: February 2017

AbstractDuring teleost ontogeny the larval and embryonic stages are key stages, since failure during this period of tissue differentiation may cause malformations, developmental delays, poor growth, and massive mortalities. Despite the rapid advances in sequencing technologies, the molecular backgrounds of the development of economically important but endangered fish species like the Atlantic sturgeon (Acipenser oxyrinchus) have not yet been thoroughly investigated. The current study examines the differential expression of transcripts involved in embryonic development of the Atlantic sturgeon. Addressing this goal, a reference transcriptome comprising eight stages was generated using an Illumina HiSequation 2500 platform. The constructed de novo assembly counted to 441,092 unfiltered and 179,564 filtered transcripts. Subsequently, the expression profile of four developmental stages ranging from early (gastrula) to late stages of prelarval development [2 d posthatching (dph)] were investigated applying an Illumina MiSeq platform. Differential expression analysis revealed distinct expression patterns among stages, especially between the two early and the two later stages. Transcripts upregulated at the two early stages were mainly enriched in transcripts linked to developmental processes, while transcripts expressed at the last two stages were mainly enriched in transcripts important to muscle contraction. Furthermore, important stage-specific expression has been detected for the hatching stage with transcripts enriched in molecule transport, and for the 2 dph stage with transcripts enriched in visual perception and lipid digestion. Our investigation represents a significant contribution to the understanding of Atlantic sturgeon embryonic development, and transcript characterization along with the differential expression results will significantly contribute to sturgeon research and aquaculture.