bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms Underlying the Enhanced Biomass and Abiotic Stress Tolerance Phenotypes of an Arabidopsis MIOX Over-expresser
Authors: Nepal Nirman , Yactayo-Chang Jessica P. , Medina-Jiménez Karina , Acosta-Gamboa Lucia M. , González-Romero María Elena , Arteaga-Vázquez Mario A. , Lorence Argelia 
Published: February 2019

AbstractMyo-inositol oxygenase (MIOX) is the first enzyme in the inositol route to ascorbate (L-ascorbic acid, AsA, vitamin C). We have previously shown that Arabidopsis plants constitutively expressing MIOX have elevated foliar AsA content and displayed enhanced growth rate, biomass accumulation, and increased tolerance to multiple abiotic stresses. In this work, we used a combination of transcriptomics, chromatography, microscopy, and physiological measurements to gain a deeper understanding of the underlying mechanisms mediating the phenotype of the AtMIOX4 line. Transcritpomic analysis revealed increased expression of genes involved in auxin synthesis, hydrolysis, transport, and metabolism, which are supported by elevated auxin levels both in vitro and in vivo, and confirmed by assays demonstrating their effect on epidermal cell elongation in the AtMIOX4 over-expresser plants. Additionally, we detected up-regulation of transcripts involved in photosynthesis that was validated by increased efficiency of the photosystem II and proton motive force. We also found increased expression of amylase leading to higher intracellular glucose levels. Multiple gene families conferring plants tolerance to cold, water limitation, and heat stresses were found to be elevated in the AtMIOX4 line. Interestingly, the high AsA plants also displayed up-regulation of transcripts and hormones involved in defense including jasmonates, defensin, glucosinolates, and transcription factors that are known to be important for biotic stress tolerance. These results overall indicate that elevated levels of auxin and glucose, and enhanced photosynthetic efficiency in combination with up-regulation of abiotic stresses response genes underly the higher growth rate and abiotic stresses tolerance phenotype of the AtMIOX4 over-expressers.
Transcriptome analysis reveals that fertilization with cryopreserved sperm downregulates genes relevant for early embryo development in the horse
Authors: Ortiz-Rodriguez JM , Ortega Ferrusola C , Gil MC , Martín Cano FE , Gaitskell-Phillips G , Rodríguez-Martínez H , Hinrichs K , Álvarez-Barrientos A , Román A , Peña FJ 
Published: February 2019

ABSTRACTArtificial insemination with cryopreserved sperm is a major assisted reproductive technology in many species. In horses, as in humans, insemination with cryopreserved sperm is associated with lower pregnancy rates than those for fresh sperm, however, direct effects of sperm cryopreservation on the development of resulting embryos are largely unexplored. The aim of this study was to investigate differences in gene expression between embryos resulting from fertilization with fresh or cryopreserved sperm. Embryos were obtained at 8, 10 or 12 days after ovulation from mares inseminated post-ovulation on successive cycles with either fresh sperm or frozen-thawed sperm from the same stallion, providing matched embryo pairs at each day. RNA was isolated from two matched pairs (4 embryos) for each day, and cDNA libraries were built and sequenced. Significant differences in transcripts per kilobase million (TPM) were determined using (i) genes for which the expression difference between treatments was higher than 99% of that in the random case (P < 0.01), and (ii) genes for which the fold change was ≥ 2, to avoid expression bias in selection of the candidate genes. Molecular pathways were explored using the DAVID webserver, followed by network analyses using STRING, with a threshold of 0.700 for positive interactions. The transcriptional profile of embryos obtained with frozen-thawed sperm differed significantly from that for embryos derived from fresh sperm on all days, showing significant down-regulation of genes involved in biological pathways related to oxidative phosphorylation, DNA binding, DNA replication, and immune response. Many genes with reduced expression were orthologs of genes known to be embryonic lethal in mice. This study, for the first time, provides evidence of altered transcription in embryos resulting from fertilization with cryopreserved spermatozoa in any species. As sperm cryopreservation is commonly used in many species, including human, the effect of this intervention on expression of developmentally important genes in resulting embryos warrants attention.
Exposure and susceptibility drive reinfection with gastrointestinal parasites in a social primate
Authors: Müller‐Klein Nadine , Heistermann Michael , Strube Christina , Franz Mathias , Schülke Oliver , Ostner Julia 
Published: February 2019

AbstractIncreased risk of infectious disease transmission has been proposed as one major cost of group living. While factors corresponding to transmission via exposure to infectious stages and susceptibility to contracting infections upon contact are relatively well understood, both aspects are rarely investigated simultaneously.Here, we assessed the influence of exposure and susceptibility measures on strongyle nematode reinfection after experimental deworming of Barbary macaques (Macaca sylvanus) (n = 57). We investigated impacts of behaviour (social bonds, grooming and ground use) and physiology (faecal glucocorticoids, urinary C‐Peptides, urinary neopterin, gastrointestinal [GI] helminth coinfection) on the likelihood of reinfection, using patch occupancy modelling and information theoretic model selection to determine the best models predicting reinfection patterns.Coinfection was the most consistent risk factor, spending time on presumably contaminated soil, interacting with many partners and forming strong same‐sex bonds also tended to increase infection risk. In contrast, strong social bonds with opposite‐sex partners had a consistently protective effect.Our results indicate that coinfections could serve as an integrative measure of individual disease susceptibility. Furthermore, we show that social contact contributes to both exposure and susceptibility to environmentally transmitted parasites, with the outcome depending on specific interaction patterns.Aplain language summaryis available for this article.
Non‐invasive analysis of tumor mutation profiles and druggable mutations by sequencing of cell free DNA of Chinese metastatic breast cancer patients
Authors: Li Shunying , Wang Baoxiao , Li Yuquan , Lai Hongna , Liu Yujie , Jin Liang 
Published: February 2019

BackgroundMetastatic breast cancer (MBC) remains an incurable disease worldwide. Tumor gene mutations have evolved and led to drug resistance in the treatment course of MBC. However, data on the mutation profiles and druggable genomic alterations of MBC remain limited, particularly among Chinese patients. Our study aimed to depict the mutation profiles and identify druggable mutations in circulating tumor DNA (ctDNA) in Chinese MBC patients.MethodsTargeted deep sequencing of a 1021‐gene panel was performed on 17 blood samples and 5 available tissue samples from 17 Chinese MBC patients.ResultsWe identified 60 somatic mutations in 17 blood samples (sensitivity 100%). Somatic mutations were identified in the blood samples of all patients, and 41.18% (7/17) of patients harbored at least one druggable mutation. A high ctDNA level in plasma is associated with shorter progression‐free survival.ConclusionTargeted deep sequencing of cell free DNA is a highly sensitive, noninvasive method to depict tumor mutation profiles, identify druggable mutations in MBC, and predict patient outcome. Our study shed light on the utility of ctDNA as noninvasive “liquid biopsy” in the management of MBC.
Systems biology identifies preserved integrity but impaired metabolism of mitochondria due to a glycolytic defect in Alzheimer's disease neurons
Authors: Theurey Pierre , Connolly Niamh M. C. , Fortunati Ilaria , Basso Emy , Lauwen Susette , Ferrante Camilla , Moreira Pinho Catarina , Joselin Alvin , Gioran Anna , Bano Daniele , Park David S. , Ankarcrona Maria , Pizzo Paola , Prehn Jochen H. M. 
Published: February 2019

AbstractMitochondrial dysfunction is implicated in most neurodegenerative diseases, including Alzheimer's disease (AD). We here combined experimental and computational approaches to investigate mitochondrial health and bioenergetic function in neurons from a double transgenic animal model of AD (PS2APP/B6.152H). Experiments in primary cortical neurons demonstrated that AD neurons had reduced mitochondrial respiratory capacity. Interestingly, the computational model predicted that this mitochondrial bioenergetic phenotype could not be explained by any defect in the mitochondrial respiratory chain (RC), but could be closely resembled by a simulated impairment in the mitochondrial NADH flux. Further computational analysis predicted that such an impairment would reduce levels of mitochondrial NADH, both in the resting state and following pharmacological manipulation of the RC. To validate these predictions, we utilized fluorescence lifetime imaging microscopy (FLIM) and autofluorescence imaging and confirmed that transgenic AD neurons had reduced mitochondrial NAD(P)H levels at rest, and impaired power of mitochondrial NAD(P)H production. Of note, FLIM measurements also highlighted reduced cytosolic NAD(P)H in these cells, and extracellular acidification experiments showed an impaired glycolytic flux. The impaired glycolytic flux was identified to be responsible for the observed mitochondrial hypometabolism, since bypassing glycolysis with pyruvate restored mitochondrial health. This study highlights the benefits of a systems biology approach when investigating complex, nonintuitive molecular processes such as mitochondrial bioenergetics, and indicates that primary cortical neurons from a transgenic AD model have reduced glycolytic flux, leading to reduced cytosolic and mitochondrial NAD(P)H and reduced mitochondrial respiratory capacity.
Copy number variation and variant discovery in Bullmastiff dogs
Authors: Mortlock S.‐A. , Williamson P. , Khatkar M. S. 
Published: February 2019

SummaryIdentification of genomic variants within dogs is important for understanding genetic factors contributing to breed diversity and phenotypic traits. This study aimed to identify sources of variation in the Bullmastiff using high‐density signal intensity and whole‐genome sequence data. Close to 3000 copy number variants (CNVs) were identified in Bullmastiff dogs using Canine HD BeadChip data. When CNVs were collated, 82 CNV regions (CNVRs) were detected, 50% in transcribed regions encompassing 432 genes. Fifty of the CNVRs detected have not been reported in other breeds and represent potential breed‐specific variants. A proportion of the CNVR variants with predicted modifying effects on gene pathways may contribute to breed traits. Approximately 5 million putative variants per dog, inclusive of single nucleotide polymorphisms (SNPs), multi‐nucleotide polymorphisms (MNPs) and insertion and deletions (INDELs), were identified from DNA sequence data on a small number of animals. Identification of genetic variants in the Bullmastiff highlights sources of variation in the breed and molecular markers that will assist in future trait and disease investigations in dogs.
Multicentre clinical simulation evaluation of the ISO 80369‐6 neuraxial non‐Luer connector
Authors: Cook T. M. , Wilkes A. , Bickford Smith P. , Dorn L. , Stacey M. , Kinsella S. M. , Sharpe P. , Phillips P. 
Published: February 2019

SummaryTo avoid potentially fatal wrong‐route neuraxial drug errors, international standard ISO 80369‐6 specifying a non‐Luer neuraxial connector design was published in 2016. We describe usability studies used in development of the design. Thirty‐eight doctors and 17 nurses performed simulated procedures on manikins, using devices fitted with Luer connectors or draft ISO 80369‐6 ‘non‐Luer’ connectors. The procedures included spinal anaesthesia; intrathecal chemotherapy; lumbar puncture, cerebrospinal fluid collection and pressure measurement; epidural catheter placement with bolus injection and critical care use. Participants attempted cross connection between neuraxial connectors and a range of other medical device connectors, including those from the ISO 80369 small‐bore connector series. Video recording analysis was used for all assessments. Participants subjectively assessed performance of the draft non‐Luer connector, including suitability for routine clinical use. Participants performed 198 procedures. The connector achieved easy, leak‐free connections. The willingness of participants to use the non‐Luer connectors were: spinal anaesthesia 100%; intrathecal chemotherapy 88%; lumbar puncture, cerebrospinal fluid collection and pressure measurement 93%; epidural catheter placement with bolus injection 78%; critical care use 100%. Concerns raised were generally device related, rather than connector related. Most cross‐connection attempts failed, even using above clinical forces and, when successful, were judged of low clinical risk potential; the exception was a malaligned connection between the non‐Luer slip and female Luer connectors. This led to revision of the dimensional tolerances of the non‐Luer connector to reduce this risk, before publication of the final specification in 2016. We conclude that the ISO 80369‐6 neuraxial non‐Luer connector is suitable for clinical use.
Phosphorylation of GATA4 serine 105 but not serine 261 is required for testosterone production in the male mouse
Authors: Bergeron F. , Boulende Sab A. , Bouchard M. F. , Taniguchi H. , Souchkova O. , Brousseau C. , Tremblay J. J. , Pilon N. , Viger R. S. 
Published: February 2019

AbstractBackgroundGATA4 is a transcription factor essential for male sex determination, testicular differentiation during fetal development, and male fertility in the adult. GATA4 exerts part of its function by regulating multiple genes in the steroidogenic enzyme pathway. In spite of these crucial roles, how the activity of this factor is regulated remains unclear.ObjectivesStudies in gonadal cell lines have shown that GATA4 is phosphorylated on at least two serine residues—serine 105 (S105) and serine 261 (S261)—and that this phosphorylation is important for GATA4 activity. The objective of the present study is to characterize the endogenous role of GATA4 S105 and S261 phosphorylation in the mouse testis.Materials and methodsWe examined both previously described GATA4 S105A mice and a novel GATA4 S261A knock‐in mouse that we generated by CRISPR/Cas9 gene editing. The male phenotype of the mutants was characterized by assessing androgen‐dependent organ weights, hormonal profiles, and expression of multiple testicular target genes using standard biochemical and molecular biology techniques.ResultsThe fecundity of crosses between GATA4 S105A mice was reduced but without a change in sex ratio. The weight of androgen‐dependent organs was smaller when compared to wild‐type controls. Plasma testosterone levels showed a 70% decrease in adult GATA4 S105A males. This decrease was associated with a reduction in Cyp11a1, Cyp17a1, and Hsd17b3 expression. GATA4 S261A mice were viable and testis morphology appeared normal. Testosterone production and steroidogenic enzyme expression were not altered in GATA4 S261A males.Discussion and conclusionOur analysis showed that blocking GATA4 S105 phosphorylation is associated with decreased androgen production in males. In contrast, S261 phosphorylation by itself is dispensable for GATA4 function. These results confirm that endogenous GATA4 action is essential for normal steroid production in males and that this activity requires phosphorylation on at least one serine residue.
Evaluation of centrifugal blood pumps in term of hemodynamic performance using simulated neonatal and pediatric ECMO circuits
Authors: Wang Shigang , Moroi Morgan K. , Kunselman Allen R. , Myers John L. , Ündar Akif 
Published: February 2019

AbstractThe objective of this translational study was to evaluate the FDA‐approved PediMag, CentriMag, and RotaFlow centrifugal blood pumps in terms of hemodynamic performance using simulated neonatal and pediatric extracorporeal membrane oxygenation (ECMO) circuits with different sizes of arterial and venous cannulae. Cost of disposable pump heads was another important variable for this particular study. The experimental circuit was composed of one of the centrifugal pump heads, a polymethylpentene membrane oxygenator, neonatal and pediatric arterial/venous cannulae, and 1/4‐inch ID tubing. Circuits were primed with lactated Ringer’s solution and packed human red blood cells (hematocrit 35%). Trials were conducted at 36°C using the three pump heads and different cannulae (arterial/venous cannulae: 8 Fr/18 Fr, 10 Fr/20 Fr, and 12 Fr/22 Fr) at various flow rates (200–2400 mL/min, 200 mL/min increments) and rotational speeds. Pseudo patient pressure was 60 mm Hg. Real‐time pressure and flow data were recorded for analysis. The RotaFlow pump had a higher pressure head and flow range compared with the PediMag and CentriMag pumps at the same rotational speed and identical experimental settings (P < 0.001). The PediMag pump had lower flow output than others (P < 0.001). Small‐caliber arterial cannulae and higher flow rates predictably created higher circuit pressures and pressure drops. There was no significant difference in hemodynamic energy delivered to the pseudo patient with each of the three pumps. The arterial cannula had the highest pressure drop and hemodynamic energy loss in the circuit when compared to the oxygenator and arterial tubing. The RotaFlow centrifugal pump had a significantly better hemodynamic performance when compared to the PediMag and CentriMag blood pumps at identical experimental conditions in simulated neonatal and pediatric ECMO settings. In addition, the cost of the RotaFlow pump head ($400) is 20 to 30‐fold less than the other centrifugal pumps [CentriMag ($12 000) or PediMag ($8000)] that were evaluated in this translational study.
Clinical outcomes in patients with hepatitis D, cirrhosis and persistent hepatitis B virus replication, and receiving long‐term tenofovir or entecavir
Authors: Brancaccio Giuseppina , Fasano Massimo , Grossi Adriano , Santantonio Teresa Antonia , Gaeta Giovanni B. 
Published: February 2019

SummaryBackgroundSuppression of hepatitis B virus (HBV) replication with nucelos(t)ide analogues should be considered for patients with chronic hepatitis D virus (HDV) infection and ongoing HBV replication.AimTo verify the clinical outcome after long‐term entecavir or tenofovir treatment in patients with advanced fibrosis/cirrhosis, ineligible to peg‐interferon therapy.MethodsPatients were prospectively followed‐up at 3‐6 month intervals; measured outcomes were decompensation, hepatocellular carcinoma (HCC), liver transplant and liver related death. HBV monoinfected patients receiving the same treatment served as reference after 1:1 matching by age, gender, platelet count, albumin level, bilirubin and INR.Results56 HDV patients (48 with cirrhosis; median follow‐up 50 months) were enrolled; all achieved HBV DNA suppression. Death or liver transplant occurred in 19 patients, with a rate (n/1000 patient‐months) of 2.92 in HDV patients vs 0.38 in HBV monoinfected patients (P < 0.001); similarly, decompensation occurred at a rate of 1.53 vs 0.13 (P = 0.015), respectively, and the rate of HCC was almost thrice in HDV cohort (3.12 vs 1.12; P = 0.02) Platelet count, Child‐Pugh score and marginally HDV infection were associated with HCC development.ConclusionPatients with HDV infection and advanced liver disease maintain an increased risk of severe clinical events as compared with HBV monoinfected patients, during prolonged HBV DNA suppression with potent NA.
Effects of different levels of dietary protein with or without plant extract YGF251 on growth performance, nutrient digestibility, blood profiles, fecal microbial shedding, and fecal gas emission in growing pigs
Authors: Lei Xin Jian , Lee Sang In , Kim In Ho 
Published: February 2019

AbstractThis experiment was conducted to evaluate the effects of plant extract YGF251 supplementation in different protein level diets on growth performance, nutrient digestibility, blood profiles, fecal microbial shedding, and fecal gas emission in growing pigs. A total of 144 pigs (24.72 ± 1.54 kg) were randomly assigned to the treatments in a 2 × 3 factorial arrangement of dietary protein levels (15.50%, 14.00% or 12.50%) and plant extract YGF251 levels (0 or 0.05%) with 6 replications per treatment and 4 pigs per pen. Pigs fed low protein diets had reduced average daily gain (p < 0.05) and increased feed conversion ratio (p < 0.01) compared with pigs fed high protein diets. The apparent total tract digestibility of nitrogen was decreased (p < 0.05) when reducing dietary protein level. Fecal ammonia and hydrogen sulfide emissions were reduced (p < 0.05) when reducing dietary protein level. In conclusion, the results of the current study indicated that reducing dietary protein level impaired growth performance and nitrogen digestibility but reduced ammonia and hydrogen sulfide emissions in growing pigs. Dietary supplementation with 0.05% herbal extract YGF251 was not effective in improving growth performance, nutrient digestibility, or in decreasing gas emission in different protein diets.
Life expectancy of follicular lymphoma patients in complete response at 30 months is similar to that of the Spanish general population
Authors: Magnano Laura , Alonso‐Alvarez Sara , Alcoceba Miguel , Rivas‐Delgado Alfredo , Muntañola Anna , Nadeu Ferran , Setoain Xavier , Rodríguez Sonia , Andrade‐Campos Marcio , Espinosa‐Lara Natalia , Rodríguez Guillermo , Sancho Juan Manuel , Moreno Miriam , Mercadal Santiago , Carro Itziar , Salar Antonio , Garcia‐Pallarols Francesc , Arranz Reyes , Cannata Jimena , Terol María J. , Teruel Ana I. , Jiménez‐Ubieto Ana , Rodriguez Antonia , González de Villambrosía Sonia , Bello José L. , López Lourdes , Novelli Silvana , de Cabo Erik , Infante María E. , Pardal Emilia , Monsalvo Silvia , González Marcos , Martín Alejandro , Caballero M. Dolores , López‐Guillermo Armando ,   the Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO)
Published: February 2019

SummaryThe use of immunochemotherapy has improved the outcome of follicular lymphoma (FL). Recently, complete response at 30 months (CR30) has been suggested as a surrogate for progression‐free survival. This study aimed to analyse the life expectancy of FL patients according to their status at 30 months from the start of treatment in comparison with the sex and age‐matched Spanish general population (relative survival; RS). The training series comprised 263 patients consecutively diagnosed with FL in a 10‐year period who needed therapy and were treated with rituximab‐containing regimens. An independent cohort of 693 FL patients from the Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO) group was used for validation. In the training cohort, 188 patients were in CR30, with a 10‐year overall survival (OS) of 53% and 87% for non‐CR30 and CR30 patients, respectively. Ten‐year RS was 73% and 100%, showing no decrease in life expectancy for CR30 patients. Multivariate analysis indicated that the FL International Prognostic Index was the most important variable predicting OS in the CR30 group. The impact of CR30 status on RS was validated in the independent GELTAMO series. In conclusion, FL patients treated with immunochemotherapy who were in CR at 30 months showed similar survival to a sex‐ and age‐matched Spanish general population.