bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming growth factor β-mediated site-specific Smad linker region phosphorylation in vascular endothelial cells
Authors: Kamato Danielle , Rostam Muhamad Ashraf , Piva Terence J , Babaahmadi Rezaei Hossein , Getachew Robel , Thach Lyna , Bernard Rebekah , Zheng Wenhua , Little Peter J , Osman Narin 
Published: October 2014

Abstract

Objectives
Transforming growth factor (TGF)-β regulates the function of vascular endothelial cells and may be involved in endothelial dysfunction. The canonical TGF-β pathway involves TGF-β receptor-mediated carboxy-terminal phosphorylation of Smad2; however, TGF-β signalling also activates numerous serine/threonine kinases that phosphorylate Smad2 in its linker region. The expression of phosphorylated Smad linker proteins were determined following TGF-β stimulation in the absence and presence of different serine/threonine kinase inhibitors in vascular endothelial cells.

Methods
Proteins were quantified by Western blotting using specific antibodies to individual phosphorylated Smad2 linker region residues.

Key findings
TGF-β mediated the phosphorylation of all four Smad2 linker region residues of interest. Erk and Jnk specifically phosphorylate Ser245 while all mitogen-activated protein kinases phosphorylate Ser250 and Ser255. Thr220 and Ser245 are phosphorylated by phosphoinositide 3 kinase (PI3K), while Ser255 was phosphorylated by the PI3K/Akt pathway. CDK and GSK-3 were shown to phosphorylate Thr220 and Ser245. TGF-β also mediated plasminogen activator inhibitor-1 gene expression that was attenuated by p38 and CDK inhibitors.

Conclusions
TGF-β-mediated phosphorylation of individual serine/threonine sites in the linker region of Smad2 occurs in a highly specific manner by kinases. These phosphorylations provide an opportunity to further understand a therapeutically targeted and very specific signalling pathway in vascular endothelial cells.
Glucose transport and milk secretion during manipulated plasma insulin and glucose concentrations and during LPS‐induced mastitis in dairy cows
Authors: Gross J. J. , van Dorland H. A. , Wellnitz O. , Bruckmaier R. M. 
Published: October 2014

SummaryIn dairy cows, glucose is essential as energy source and substrate for milk constituents. The objective of this study was to investigate effects of long‐term manipulated glucose and insulin concentrations in combination with a LPS‐induced mastitis on mRNA abundance of glucose transporters and factors involved in milk composition. Focusing on direct effects of insulin and glucose without influence of periparturient endocrine adaptations, 18 dairy cows (28 ± 6 weeks of lactation) were randomly assigned to one of three infusion treatments for 56 h (six animals each). Treatments included a hyperinsulinemic hypoglycaemic clamp (HypoG), a hyperinsulinemic euglycaemic clamp (EuG) and a control group (NaCl). After 48 h of infusions, an intramammary challenge with LPS from E. coli was performed and infusions continued for additional 8 h. Mammary gland biopsies were taken before, at 48 (before LPS challenge) and at 56 h (after LPS challenge) of infusion, and mRNA abundance of genes involved in mammary gland metabolism was measured by RT‐qPCR. During the 48 h of infusions, mRNA abundance of glucose transporters GLUT1, 3, 4, 8, 12, SGLT1, 2) was not affected in HypoG, while they were downregulated in EuG. The mRNA abundance of alpha‐lactalbumin, insulin‐induced gene 1, κ‐casein and acetyl‐CoA carboxylase was downregulated in HypoG, but not affected in EuG. Contrary during the intramammary LPS challenge, most of the glucose transporters were downregulated in NaCl and HypoG, but not in EuG. The mRNA abundance of glucose transporters in the mammary gland seems not to be affected by a shortage of glucose, while enzymes and milk constituents directly depending on glucose as a substrate are immediately downregulated. During LPS‐induced mastitis in combination with hypoglycaemia, mammary gland metabolism was more aligned to save glucose for the immune system compared to a situation without limited glucose availability during EuG.
Dynamic Clinical Measurements of Voluntary Vaginal Contractions and Autonomic Vaginal Reflexes
Authors: Broens Paul M.A. , Spoelstra Symen K. , Weijmar Schultz Willibrord C.M. 
Published: October 2014

Abstract

Introduction
The vaginal canal is an active and responsive canal. It has pressure variations along its length and shows reflex activity. At present, the prevailing idea is that the vaginal canal does not have a sphincter mechanism. It is hypothesized that an active vaginal muscular mechanism exists and might be involved in the pathophysiology of genito-pelvic pain/penetration disorder.

Aim
The aim of this study was to detect the presence of a canalicular vaginal “sphincter mechanism” by measuring intravaginal pressure at different levels of the vaginal canal during voluntary pelvic floor contractions and during induced reflexive contractions.

Methods
Sixteen nulliparous women, without sexual dysfunction and pelvic floor trauma, were included in the study. High-resolution solid-state circumferential catheters were used to measure intravaginal pressures and vaginal contractions at different levels in the vaginal canal. Voluntary intravaginal pressure measurements were performed in the left lateral recumbent position only, while reflexive intravaginal pressure measurements during slow inflation of a vaginal balloon were performed in the left lateral recumbent position and in the sitting position.

Main Outcome Measures
Intravaginal pressures and vaginal contractions were the main outcome measures. In addition, a general demographic and medical history questionnaire was administered to gain insight into the characteristics of the study population.

Results
Fifteen out of the sixteen women had deep and superficial vaginal high-pressure zones. In one woman, no superficial high-pressure zone was found. The basal and maximum pressures, as well as the duration of the autonomic reflexive contractions significantly exceeded the pressures and the duration of the voluntary contractions. There were no significant differences between the reflexive measurements obtained in the left lateral recumbent and the sitting position.

Conclusion
The two high-pressure zones found in this study, as a result of voluntary contractions and, even more pronounced, as a result of reflexive contractions on intravaginal stimulation, support the hypothesis that the vaginal canal has an active and passive canalicular sphincter mechanism. Further investigation of this sphincter mechanism is required to identify its role in the sexual response and genito-pelvic pain/penetration disorder.
Prevalence of Chiari‐like Malformations in Clinically Unaffected Dogs
Authors: Harcourt‐Brown T.R. , Campbell J. , Warren‐Smith C. , Jeffery N.D. , Granger N.P. 
Published: October 2014

BackgroundThe importance of Chiari‐like malformation (CM) in the generation of clinical signs or the formation of syringomyelia in dogs is incompletely understood, partly because the prevalence of various CM definitions in unaffected dogs is unknown.Hypothesis/ObjectivesThe aims were: to estimate the prevalence of CM in dogs asymptomatic for CM or syringomyelia, according to 3 currently used definitions; and, to investigate the effect of brachycephaly and head position during magnetic resonance (MR) imaging on estimates of the prevalence of CM.AnimalsOne ninety‐nine client‐owned dogs without apparent signs of CM or syringomyelia.MethodsBlinded, retrospective analysis. Archived MR images were analyzed for evidence of cerebellar indentation and impaction into or herniation through the foramen magnum. Logistic regression analysis was used to investigate the relationship of CM diagnosis with head position and the cranial index (a measure of brachycephaly).ResultsIn 185 non‐Cavalier King Charles Spaniel (CKCS) dogs, indentation was identified in 44% (95% CI, 47–51%) and impaction in 22% (95% CI, 16–28%). No asymptomatic, non‐CKCS dogs showed herniation. Regression analysis showed a significant increase in the odds of indentation and impaction in an extended head position and as the cranial index increased (became more brachycephalic).Conclusions and Clinical ImportanceThe high prevalence of cerebellar indentation and impaction suggests that they may be normal anatomical variations and therefore unsuitable as definitions of CM. We suggest that future research into CM in dogs should define cases and controls more strictly so that overlap between normal and abnormal animals is minimized.
Molecular basis for the reverse reaction of African human trypanosomes glycerol kinase
Authors: Balogun Emmanuel Oluwadare , Inaoka Daniel Ken , Shiba Tomoo , Kido Yasutoshi , Tsuge Chiaki , Nara Takeshi , Aoki Takashi , Honma Teruki , Tanaka Akiko , Inoue Masayuki , Matsuoka Shigeru , Michels Paul A. M. , Kita Kiyoshi , Harada Shigeharu 
Published: October 2014

SummaryThe glycerol kinase (GK) of African human trypanosomes is compartmentalized in their glycosomes. Unlike the host GK, which under physiological conditions catalyzes only the forward reaction (ATP‐dependent glycerol phosphorylation), trypanosome GK can additionally catalyze the reverse reaction. In fact, owing to this unique reverse catalysis, GK is potentially essential for the parasites survival in the human host, hence a promising drug target. The mechanism of its reverse catalysis was unknown; therefore, it was not clear if this ability was purely due to its localization in the organelles or whether structure‐based catalytic differences also contribute. To investigate this lack of information, the X‐ray crystal structure of this protein was determined up to 1.90 Å resolution, in its unligated form and in complex with three natural ligands. These data, in conjunction with results from structure‐guided mutagenesis suggests that the trypanosome GK is possibly a transiently autophosphorylating threonine kinase, with the catalytic site formed by non‐conserved residues. Our results provide a series of structural peculiarities of this enzyme, and gives unexpected insight into the reverse catalysis mechanism. Together, they provide an encouraging molecular framework for the development of trypanosome GK‐specific inhibitors, which may lead to the design of new and safer trypanocidal drug(s).
Magnesium as an adjuvant for caudal analgesia in children
Authors: Kim Eun Mi , Kim Min‐Soo , Han Seok‐Joo , Moon Bong Ki , Choi Eun Mi , Kim Eun Ho , Lee Jeong‐Rim 
Published: October 2014

SummaryBackgroundThere is a need for an adjuvant agent of caudal block that prolongs its duration and improves the analgesic efficacy to fasten functional recovery. Magnesium is an N‐methyl‐D‐aspartate receptor antagonist that functions as an analgesic. This study was aimed to evaluate whether magnesium as an adjuvant for caudal block in children can improve postoperative analgesia and functional recovery.MethodsEighty children, 2–6 years of age, undergoing inguinal herniorrhaphy, were included in this prospective, randomized, double‐blinded study. For caudal block, Group R received ropivacaine 1.5 mg·ml−1, 1 ml·kg−1 and Group RM received the same dose of ropivacaine mixed with 50 mg of magnesium. The Parents' Postoperative Pain Measure (PPPM) score, analgesic consumption, functional recovery, and adverse effects were evaluated at 6, 24, 48, and 72 h after surgery, as well as daily thereafter until the child showed full functional recovery.ResultsThe PPPM score after hospital discharge was significantly lower for Group RM than for Group R at all times (P < 0.05). Children in Group RM required less fentanyl for rescue analgesia in the recovery area (16.2% vs 39.5%, P = 0.034) and less oral analgesics after discharge (20.5% vs 52.6%, P = 0.007). The time to return of normal functional activity was shorter in Group RM (P < 0.05). The incidence of adverse effects did not differ between groups.ConclusionsAs an adjuvant for caudal analgesia, 50 mg magnesium provided superior quality of analgesia and faster return of normal functional activity than local anesthetic alone in children.
Quotient closed subcategories of quiver representations
Authors: Oppermann Steffen , Reiten Idun , Thomas Hugh 
Published: October 2014

AbstractLet $Q$ be a finite quiver without oriented cycles, and let $k$ be an algebraically closed field. The main result in this paper is that there is a natural bijection between the elements in the associated Weyl group $W_{Q}$ and the cofinite additive quotient closed subcategories of the category of finite dimensional right modules over $kQ$. We prove this correspondence by linking these subcategories to certain ideals in the preprojective algebra associated to $Q$, which are also indexed by elements of $W_{Q}$.
Confirmation of a realistic reactor model for BNCT dosimetry at the TRIGA Mainz
Authors: Ziegner Markus , Schmitz Tobias , Khan Rustam , Blaickner Matthias , Palmans Hugo , Sharpe Peter , Hampel Gabriele , Böck Helmuth 
Published: October 2014

Purpose:In order to build up a reliable dose monitoring system for boron neutron capture therapy (BNCT) applications at the TRIGA reactor in Mainz, a computer model for the entire reactor was established, simulating the radiation field by means of the Monte Carlo method. The impact of different source definition techniques was compared and the model was validated by experimental fluence and dose determinations.Methods:The depletion calculation code origen2 was used to compute the burn‐up and relevant material composition of each burned fuel element from the day of first reactor operation to its current core. The material composition of the current core was used in a mcnp5 model of the initial core developed earlier. To perform calculations for the region outside the reactor core, the model was expanded to include the thermal column and compared with the previously established attila model. Subsequently, the computational model is simplified in order to reduce the calculation time. Both simulation models are validated by experiments with different setups using alanine dosimetry and gold activation measurements with two different types of phantoms.Results:The mcnp5 simulated neutron spectrum and source strength are found to be in good agreement with the previous attila model whereas the photon production is much lower. Both mcnp5 simulation models predict all experimental dose values with an accuracy of about 5%. The simulations reveal that a Teflon environment favorably reduces the gamma dose component as compared to a polymethyl methacrylate phantom.Conclusions:A computer model for BNCT dosimetry was established, allowing the prediction of dosimetric quantities without further calibration and within a reasonable computation time for clinical applications. The good agreement between the mcnp5 simulations and experiments demonstrates that the attila model overestimates the gamma dose contribution. The detailed model can be used for the planning of structural modifications in the thermal column irradiation channel or the use of different irradiation sites than the thermal column, e.g., the beam tubes.
Evaluating the purity of a 57Co flood source by PET
Authors: DiFilippo Frank P. 
Published: October 2014

Purpose:Flood sources of 57Co are commonly used for quality control of gamma cameras. Flood uniformity may be affected by the contaminants 56Co and 58Co, which emit higher energy photons. Although vendors specify a maximum combined 56Co and 58Co activity, a convenient test for flood source purity that is feasible in a clinical environment would be desirable.Methods:Both 56Co and 58Co emit positrons with branching 19.6% and 14.9%, respectively. As is known from 90Y imaging, a positron emission tomography (PET) scanner is capable of quantitatively imaging very weak positron emission in a high single‐photon background. To evaluate this approach, two 57Co flood sources were scanned with a clinical PET/CT multiple times over a period of months. The 56Co and 58Co activity was clearly visible in the reconstructed PET images. Total impurity activity was quantified from the PET images after background subtraction of prompt gamma coincidences.Results:Time‐of‐flight PET reconstruction was highly beneficial for accurate image quantification. Repeated measurements of the positron‐emitting impurities showed excellent agreement with an exponential decay model. For both flood sources studied, the fit parameters indicated a zero intercept and a decay half‐life consistent with a mixture of 56Co and 58Co. The total impurity activity at the reference date was estimated to be 0.06% and 0.07% for the two sources, which was consistent with the vendor's specification of <0.12%.Conclusions:The robustness of the repeated measurements and a thorough analysis of the detector corrections and physics suggest that the accuracy is acceptable and that the technique is feasible. Further work is needed to validate the accuracy of this technique with a calibrated high resolution gamma spectrometer as a gold standard, which was not available for this study, and for other PET detector models.
Global Survey of Canonical Aspergillus flavus G Protein-Coupled Receptors
Authors: Affeldt Katharyn J. , Carrig Joseph , Amare Meareg , Keller Nancy P. 
Published: October 2014

ABSTRACT

G protein-coupled receptors (GPCRs) are transmembrane receptors that relay signals from the external environment inside the cell, allowing an organism to adapt to its surroundings. They are known to detect a vast array of ligands, including sugars, amino acids, pheromone peptides, nitrogen sources, oxylipins, and light. Despite their prevalence in fungal genomes, very little is known about the functions of filamentous fungal GPCRs. Here we present the first full-genome assessment of fungal GPCRs through characterization of null mutants of all 15 GPCRs encoded by the aflatoxin-producing fungus
Aspergillus flavus
. All strains were assessed for growth, development, ability to produce aflatoxin, and response to carbon sources, nitrogen sources, stress agents, and lipids. Most GPCR mutants were aberrant in one or more response processes, possibly indicative of cross talk in downstream signaling pathways. Interestingly, the biological defects of the mutants did not correspond with assignment to established GPCR classes; this is likely due to the paucity of data for characterized fungal GPCRs. Many of the GPCR transcripts were differentially regulated under various conditions as well. The data presented here provide an extensive overview of the full set of GPCRs encoded by
A. flavus
and provide a framework for analysis in other fungal species.

IMPORTANCE
Aspergillus flavus
is an opportunistic pathogen of crops and animals, including humans, and it produces a carcinogenic toxin called aflatoxin. Because of this,
A. flavus
accounts for food shortages and economic losses in addition to sickness and death. Effective means of combating this pathogen are needed to mitigate its deleterious effects. G protein-coupled receptors (GPCRs) are often used as therapeutic targets due to their signal specificity, and it is estimated that half of all drugs target GPCRs. In fungi such as
A. flavus
, GPCRs are likely necessary for sensing the changes in the environment, including food sources, developmental signals, stress agents, and signals from other organisms. Therefore, elucidating their functions in
A. flavus
could identify ideal receptors against which to develop antagonists.
An Avian H7N1 Gain-of-Function Experiment of Great Concern
Authors: Wain-Hobson Simon 
Published: October 2014

ABSTRACT
Inappropriately named gain-of-function influenza research seeks to confer airborne transmission on avian influenza A viruses that otherwise cause only dead-end infections in humans. A recent study has succeeded in doing this with a highly pathogenic ostrich H7N1 virus in a ferret model without loss of virulence. If transposable to humans, this would constitute a novel virus with a case fatality rate ~30 greater than that of Spanish flu. A commentary from three distinguished virologists considered the benefits of this work to outweigh potential risks. I beg to disagree with conclusions in both papers, for the underlying science is not as strong as it appears.
Sexual violence and neonatal outcomes: a Norwegian population-based cohort study
Authors: Henriksen Lena , Schei Berit , Vangen Siri , Lukasse Mirjam 
Published: October 2014

ObjectiveThe objective of this study was to explore the association between sexual violence and neonatal outcomes.DesignNational cohort study.SettingWomen were recruited to the Norwegian Mother and Child Cohort Study (MoBa) while attending routine ultrasound examinations from 1999 to 2008.PopulationA total of 76 870 pregnant women.MethodsSexual violence and maternal characteristics were self-reported in postal questionnaires during pregnancy. Neonatal outcomes were retrieved from the Medical Birth Registry of Norway (MBRN). Risk estimations were performed with linear and logistic regression analysis. Outcome measures: gestational age at birth, birth weight, preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA).ResultsOf 76 870 women, 18.4% reported a history of sexual violence. A total of 4.7% delivered prematurely, 2.7% had children with a birth weight <2500 g and 8.1% children were small for their gestational age. Women reporting moderate or severe sexual violence (rape) had a significantly reduced gestational length (2 days) when the birth was provider-initiated in an analysis adjusted for age, parity, education, smoking, body mass index and mental distress. Those exposed to severe sexual violence had a significantly reduced gestational length of 0.51 days with a spontaneous start of birth. Crude estimates showed that severe sexual violence was associated with PTB, LBW and SGA. When controlling for the aforementioned sociodemographic and behavioural factors, the association was no longer significant.ConclusionsSexual violence was not associated with adverse neonatal outcomes. Moderate and severe violence had a small but significant effect on gestational age; however, the clinical influence of this finding is most likely limited. Women exposed to sexual violence in this study reported more of the sociodemographic and behavioural factors associated with PTB, LBW and SGA compared with non-abused women.