bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of glucagon receptor occupancy by Positron Emission Tomography in non-human primates
Authors: Eriksson Olof , Velikyan Irina , Haack Torsten , Bossart Martin , Evers Andreas , Laitinen Iina , Larsen Philip J. , Plettenburg Oliver , Takano Akihiro , Halldin Christer , Antoni Gunnar , Johansson Lars , Pierrou Stefan , Wagner Michael 
Published: October 2019

AbstractThe glucagon receptor (GCGR) is an emerging target in anti-diabetic therapy. Reliable biomarkers for in vivo activity on the GCGR, in the setting of dual glucagon-like peptide 1/glucagon (GLP-1/GCG) receptor agonism, are currently unavailable. Here, we investigated [68Ga]Ga-DO3A-S01-GCG as a biomarker for GCGR occupancy in liver, the tissue with highest GCGR expression, in non-human primates (NHP) by PET. [68Ga]Ga-DO3A-S01-GCG was evaluated by dynamic PET in NHPs by a dose escalation study design, where up to 67 µg/kg DO3A-S01-GCG peptide mass was co-injected. The test-retest reproducibility of [68Ga]Ga-DO3A-S01-GCG binding in liver was evaluated. Furthermore, we investigated the effect of pre-treatment with acylated glucagon agonist 1-GCG on [68Ga]Ga-DO3A-S01-GCG binding in liver. [68Ga]Ga-DO3A-S01-GCG bound to liver in vivo in a dose-dependent manner. Negligible peptide mass effect was observed for DO3A-S01-GCG doses <0.2 µg/kg. In vivo Kd for [68Ga]Ga-DO3A-S01-GCG corresponded to 0.7 µg/kg, which indicates high potency. The test-retest reproducibility for [68Ga]Ga-DO3A-S01-GCG binding in liver was 5.7 ± 7.9%. Pre-treatment with 1-GCG, an acylated glucagon agonist, resulted in a GCGR occupancy of 61.5 ± 9.1% in liver. Predicted human radiation dosimetry would allow for repeated annual [68Ga]Ga-DO3A-S01-GCG PET examinations. In summary, PET radioligand [68Ga]Ga-DO3A-S01-GCG is a quantitative biomarker of in vivo GCGR occupancy.
Simultaneous electrophysiological and morphological assessment of functional damage to neural networks in vitro after 30–300 g impacts
Authors: Rogers Edmond A. , Gross Guenter W. 
Published: October 2019

AbstractAn enigma of mild traumatic brain injury are observations of substantial behavior and performance deficits in the absence of bleeding or other observable structural damage. Altered behavior and performance reflect changes in action potential (AP) patterns within neuronal networks, which could result from subtle subcellular responses that affect synaptic efficacy and AP production. The aim of this study was to investigate and quantify network activity changes after simulated concussions in vitro and therewith develop a platform for simultaneous and direct observations of morphological and electrophysiological changes in neural networks. We used spontaneously active networks grown on microelectrode arrays (MEAs) to allow long-term multisite monitoring with simultaneous optical observations before and after impacts delivered by a ballistic pendulum (30 to 300 g accelerations). The monitoring of AP waveshape templates for long periods before and after impact provided an internal control for cell death or loss of cell-electrode coupling in the observed set of neurons. Network activity patterns were linked in real-time to high power phase contrast microscopy. There was no overt loss of glial or neuronal adhesion, even at high-g impacts. All recording experiments showed repeatable spike production responses: a loss of activity with recovery to near reference in 1 hr, followed by a slow activity decay to a stable, level plateau approximately 30–40% below reference. The initial recovery occurred in two steps: a rapid return of activity to an average 24% below reference, forming a level plateau lasting from 5 to 20 min, followed by a climb to within 10% of reference where a second plateau was established for 1 to 2 hrs. Cross correlation profiles revealed changes in firing hierarchy as well as in Phase 1 in spontaneous network oscillations that were reduced by as much as 20% 6–8 min post impact with only a partial recovery at 30 min. We also observed that normally stable nuclei developed irregular rotational motion after impact in 27 out of 30 networks. The evolution of network activity deficits and recovery can be linked with microscopically observable changes in the very cells that are generating the activity. The repeatable electrophysiological impact response profiles and oscillation changes can provide a quantitative basis for systematic evaluations of pharmacological intervention strategies. Future expansion to include fluorescent microscopy should allow detailed investigations of damage mechanisms on the subcellular level.
Predictors and their prognostic value for no ROSC and mortality after a non-cardiac surgery intraoperative cardiac arrest: a retrospective cohort study
Authors: Vane Matheus F. , Carmona Maria J. C. , Pereira Sergio M. , Kern Karl B. , Timerman Sérgio , Perez Guilherme , Vane Luiz Antonio , Otsuki Denise Aya , Auler Jr José O. C. 
Published: October 2019

AbstractData on predictors of intraoperative cardiac arrest (ICA) outcomes are scarce in the literature. This study analysed predictors of poor outcome and their prognostic value after an ICA. Clinical and laboratory data before and 24 hours (h) after ICA were analysed as predictors for no return of spontaneous circulation (ROSC) and 24 h and 1-year mortality. Receiver operating characteristic curves for each predictor and sensitivity, specificity, positive and negative likelihood ratios, and post-test probability were calculated. A total of 167,574 anaesthetic procedures were performed, including 158 cases of ICAs. Based on the predictors for no ROSC, a threshold of 13 minutes of ICA yielded the highest area under curve (AUC) (0.867[0.80–0.93]), with a sensitivity and specificity of 78.4% [69.6–86.3%] and 89.3% [80.4–96.4%], respectively. For the 1-year mortality, the GCS without the verbal component 24 h after an ICA had the highest AUC (0.616 [0.792–0.956]), with a sensitivity of 79.3% [65.5–93.1%] and specificity of 86.1 [74.4–95.4]. ICA duration and GCS 24 h after the event had the best prognostic value for no ROSC and 1-year mortality. For 24 h mortality, no predictors had prognostic value.
Polystyrene nanoplastics disrupt glucose metabolism and cortisol levels with a possible link to behavioural changes in larval zebrafish
Authors: Brun Nadja R. , van Hage Patrick , Hunting Ellard R. , Haramis Anna-Pavlina G. , Vink Suzanne C. , Vijver Martina G. , Schaaf Marcel J. M. , Tudorache Christian 
Published: October 2019

AbstractPlastic nanoparticles originating from weathering plastic waste are emerging contaminants in aquatic environments, with unknown modes of action in aquatic organisms. Recent studies suggest that internalised nanoplastics may disrupt processes related to energy metabolism. Such disruption can be crucial for organisms during development and may ultimately lead to changes in behaviour. Here, we investigated the link between polystyrene nanoplastic (PSNP)-induced signalling events and behavioural changes. Larval zebrafish exhibited PSNP accumulation in the pancreas, which coincided with a decreased glucose level. By using hyperglycemic and glucocorticoid receptor (Gr) mutant larvae, we demonstrate that the PSNP-induced disruption in glucose homoeostasis coincided with increased cortisol secretion and hyperactivity in challenge phases. Our work sheds new light on a potential mechanism underlying nanoplastics toxicity in fish, suggesting that the adverse effect of PSNPs are at least in part mediated by Gr activation in response to disrupted glucose homeostasis, ultimately leading to aberrant locomotor activity.
Structural characterization of HypX responsible for CO biosynthesis in the maturation of NiFe-hydrogenase
Authors: Muraki Norifumi , Ishii Kentaro , Uchiyama Susumu , Itoh Satoru G. , Okumura Hisashi , Aono Shigetoshi 
Published: October 2019

AbstractSeveral accessory proteins are required for the assembly of the metal centers in hydrogenases. In NiFe-hydrogenases, CO and CN− are coordinated to the Fe in the NiFe dinuclear cluster of the active center. Though these diatomic ligands are biosynthesized enzymatically, detail mechanisms of their biosynthesis remain unclear. Here, we report the structural characterization of HypX responsible for CO biosynthesis to assemble the active site of NiFe hydrogenase. CoA is constitutionally bound in HypX. Structural characterization of HypX suggests that the formyl-group transfer will take place from N10-formyl-THF to CoA to form formyl-CoA in the N-terminal domain of HypX, followed by decarbonylation of formyl-CoA to produce CO in the C-terminal domain though the direct experimental results are not available yet. The conformation of CoA accommodated in the continuous cavity connecting the N- and C-terminal domains will interconvert between the extended and the folded conformations for HypX catalysis.
Ketamine induces endoplasmic reticulum stress in rats and SV-HUC-1 human uroepithelial cells by activating NLRP3/TXNIP aix
Authors: Cui Lingjuan , Jiang Xiaoyan , Zhang Chengjun , Li Danxia , Yu Shengqiang , Wan Fengchun , Ma Yue , Guo Wei , Shan Zhengfei 
Published: October 2019

AbstractMany clinical studies have been conducted on ketamine-associated cystitis. However, the underlying mechanisms of ketamine-associated cystitis still remain unclear. Bladder tissues of rats were stained by Hematoxylin and Eosin (HE). The viability of human uroepithelial cells (SV-HUC-1 cells) was determined by cell counting kit-8 (CCK-8). Apoptosis and reactive oxygen species (ROS) were examined by flow cytometry. Additionally, the expressions of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β and IL-18 were respectively determined by reverse transcription quantitative (RTq)-PCR and enzyme-linked immunosorbent assay (ELISA). The mRNA and protein levels of B-cell lymphoma/leukemia-2 (Bcl2), Bcl-2-associated X protein (Bax), cleaved caspase 3, glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP), NOD-like receptor 3 (NLRP3), thioredoxin-interacting protein (TXNIP), Catalase and MnSOD were examined by RT-qPCR and Western blot. Small interfering RNA target TXNIP transfection was performed using Lipofectamine™ 2000. We found that ketamine effectively damaged bladder tissues of rats and promoted apoptosis through regulating the expression levels of GRP78, CHOP, Bcl-2, Bax and cleaved Caspase-3 proteins in vivo and in vitro. NLRP3 inflammatory body and TXNIP were activated by ketamine, which was supported by the changes in TNF-α, IL-6, IL-1 and IL-18 in vivo and in vitro. Furthermore, knocking down TXNIP reversed the effects of ketamine on apoptosis and NLRP3 inflammatory body in SV-HUC-1 cells. Meanwhile, the changes of Catalase and MnSOD showed that ROS was enhanced by ketamine, however, such an effect was ameliorated by down-regulation of TXNIP in SV-HUC-1 cells. Ketamine promoted cell apoptosis and induced inflammation in vivo and in vitro by regulating NLRP3/TXNIP aix.
A novel missense variant c.G644A (p.G215E) of the RPGR gene in a Chinese family causes X-linked retinitis pigmentosa
Authors: Fu Jiewen , Cheng Jingliang , Zhou Qi , Wei Chunli , Chen Hanchun , Lv Hongbin , Fu Junjiang 
Published: October 2019

Abstract
The mutations in patients with X-linked retinitis pigmentosa (xlRP) have not been well described in the Chinese population. In the present study, a five-generation Chinese retinitis pigmentosa (RP) family was recruited; targeted next-generation sequencing (TGS) was used to identify causative genes and Sanger sequencing for co-segregation. RNA-seq data analysis and revere transcriptional-polymerase chain reaction (RT-PCR) were applied to investigate gene expression patterns of RP GTPase regulator (RPGR) in human and Rpgr in mouse. A novel, hemizygous, deleterious and missense variant: c.G644A (p.G215E) in the RPGR gene (NM_000328.2) exon 7 of X-chromosome was identified in the proband, which was co-segregated with the clinical phenotypes in this family. RNA-seq data showed that RPGR is ubiquitously expressed in 27 human tissues with testis in highest, but no eye tissues data. Then the expressions for Rpgr mRNA in mice including eye tissues were conducted and showed that Rpgr transcript is ubiquitously expressed very highly in retina and testis, and highly in other eye tissues including lens, sclera, and cornea; and expressed highly in the six different developmental times of retinal tissue. Ubiquitous expression in different tissues from eye and very high expression in the retina indicated that RPGR plays a vital role in eye functions, particularly in retina. In conclusion, our study is the first to indicate that the novel missense variant c.G644A (p.G215E) in the RPGR gene might be the disease-causing mutation in this xlRP family, expanding mutation spectrum. These findings facilitate better understanding of the molecular pathogenesis of this disease; provide new insights for genetic counseling and healthcare.
Association between PHOX2B gene rs28647582 T&gt;C polymorphism and Wilms tumor susceptibility
Authors: Lin Ao , Fu Wen , Wang Wenwen , Zhu Jinhong , Liu Jiabin , Xia Huimin , Liu Guochang , He Jing 
Published: October 2019

Abstract
Wilms tumor is one of the most common pediatric solid tumors. The pair-like homeobox 2b (PHOX2B) gene is an important transcription factor that regulates cellular proliferation and differentiation in early life. The association between PHOX2B single nucleotide polymorphisms (SNPs) and Wilms tumor risk has not been investigated. Therefore, we conducted a case-control study involving 145 Wilms tumor patients and 531 controls to explore the association between the PHOX2B rs28647582 T&gt;C polymorphism and Wilms tumor susceptibility. The association between the PHOX2B rs28647582 T&gt;C polymorphism and Wilms tumor susceptibility was assessed by odds ratios (ORs) and 95% confidence intervals (CIs). Our results indicated that PHOX2B rs28647582 T&gt;C polymorphism did not significantly alter Wilms tumor susceptibility. However, in the stratified analysis, we found that TC/CC genotypes significantly increased Wilms tumor risk among children older than 18 months (adjusted OR = 1.77, 95% CI = 1.07–2.95, P=0.027) and those with clinical stages III+IV (adjusted OR = 1.75, 95% CI = 1.09–2.82, P=0.022), when compared with those with TT genotype. Our study suggested that PHOX2B rs28647582 T&gt;C was weakly associated with Wilms tumor susceptibility. Our conclusions need further validation with a larger sample size.
Particulate matter exposure aggravates osteoarthritis severity
Authors: Peng Kuo-Ti , Liu Ju-Fang , Chiang Yao-Chang , Chen Pei-Chun , Chiang Ming-Hsien , Shih Hsin-Nung , Chang Pey-Jium , Lee Chiang-Wen 
Published: October 2019

Abstract
Several diseases have been linked to particulate matter (PM) exposure. Outdoor activities, such as road running or jogging, are popular aerobic exercises due to few participatory limitations. Osteoarthritis (OA) is a progressive degenerative joint disease, usually observed at age 40, and not noticed before pain or diagnosis. Although exercise has health benefits, it is unclear whether outdoor jogging in higher PM (standard reference material 1649b, SRM 1649b) concentration environments could affect OA development or severity. Hence, a PM exposure monosodium iodoacetate (MIA)-induced OA animal jogged model was established for investigation. Results showed that high doses of PM (5 mg) significantly increased pro-inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-6, and M1 macrophages in the lung region, also obtained in systemic IL-6 and TNF-α expressions in this MIA-OA rat model. Moreover, levels of osteocalcin, cartilage oligomeric matrix protein (COMP), and N-telopeptides of type I collagen were especially influenced in MIA+PM groups. Morphological and structural changes of the knee joint were detected by micro-computed tomography images (micro-CT) and immunohistochemistry. MIA + PM rats exhibited severe bone density decrease, cartilage wear, and structure damages, accompanied by lower levels of physical activity, than the sham group and groups receiving MIA or PM alone. The findings suggest that the severity of OA could be promoted by PM exposure with a PM concentration effect via systemic inflammatory mechanisms. To the best of our knowledge, this is the first study to provide direct effects of PM exposure on OA severity.
Lack of adipose-specific hexose-6-phosphate dehydrogenase causes inactivation of adipose glucocorticoids and improves metabolic phenotype in mice
Authors: Wang Jian , Wang Ying , Liu Limei , Lutfy Kabirullah , Friedman Theodore C. , Liu Ya , Jiang Meisheng , Liu Yanjun 
Published: October 2019

Abstract
Excessive glucocorticoid (GC) production in adipose tissue promotes the development of visceral obesity and metabolic syndrome (MS). 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) is critical for controlling intracellular GC production, and this process is tightly regulated by hexose-6-phosphate dehydrogenase (H6PDH). To better understand the integrated molecular physiological effects of adipose H6PDH, we created a tissue-specific knockout of the H6PDH gene mouse model in adipocytes (adipocyte-specific conditional knockout of H6PDH (H6PDHAcKO) mice). H6PDHAcKO mice exhibited almost complete absence of H6PDH expression and decreased intra-adipose corticosterone production with a reduction in 11β-HSD1 activity in adipose tissue. These mice also had decreased abdominal fat mass, which was paralleled by decreased adipose lipogenic acetyl-CoA carboxylase (ACC) and ATP-citrate lyase (ACL) gene expression and reduction in their transcription factor C/EBPα mRNA levels. Moreover, H6PDHAcKO mice also had reduced fasting blood glucose levels, increased glucose tolerance, and increased insulin sensitivity. In addition, plasma free fatty acid (FFA) levels were decreased with a concomitant decrease in the expression of lipase adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) in adipose tissue. These results indicate that inactivation of adipocyte H6PDH expression is sufficient to cause intra-adipose GC inactivation that leads to a favorable pattern of metabolic phenotypes. These data suggest that H6PDHAcKO mice may provide a good model for studying the potential contributions of fat-specific H6PDH inhibition to improve the metabolic phenotype in vivo. Our study suggests that suppression or inactivation of H6PDH expression in adipocytes could be an effective intervention for treating obesity and diabetes.
Rotational evolution of solar-type protostars during the star-disk interaction phase
Authors: Gallet F. , Zanni C. , Amard L. 
Published: October 2019

Context. The early pre-main sequence phase during which solar-mass stars are still likely surrounded by an accretion disk represents a puzzling stage of their rotational evolution. While solar-mass stars are accreting and contracting, they do not seem to spin up substantially.
Aims. It is usually assumed that the magnetospheric star-disk interaction tends to maintain the stellar rotation period constant (“disk-locking”), but this hypothesis has never been thoroughly verified. Our aim is to investigate the impact of the star-disk interaction mechanism on the stellar spin evolution during the accreting pre-main sequence phases.
Methods. We devised a model for the torques acting on the stellar envelope based on studies of stellar winds, and we developed a new prescription for the star-disk coupling founded on numerical simulations of star-disk interaction and magnetospheric ejections. We then used this torque model to follow the long-term evolution of the stellar rotation.
Results. Strong dipolar magnetic field components up to a few kG are required to extract enough angular momentum so as to keep the surface rotation rate of solar-type stars approximately constant for a few Myr. Furthermore an efficient enough spin-down torque can be provided by either one of the following: a stellar wind with a mass outflow rate corresponding to ≈10% of the accretion rate, or a lighter stellar wind combined with a disk that is truncated around the corotation radius entering a propeller regime.
Conclusions. Magnetospheric ejections and accretion powered stellar winds play an important role in the spin evolution of solar-type stars. However, kG dipolar magnetic fields are neither uncommon or ubiquitous. Besides, it is unclear how massive stellar winds can be powered while numerical models of the propeller regime display a strong variability that has no observational confirmation. Better observational statistics and more realistic models could contribute to help lessen our calculations’ requirements.
Hundebesitzer überwiegend zufrieden mit Radiotherapie ihrer Hunde
Authors: Schürg Andrea 
Published: October 2019

Serras AR, Berlato D, Murphy S. Owners‘ perception of their dogs‘ quality of life during and after radiotherapy for cancer. J Small Anim Pract 2019; 60: 268–273.
Krebserkrankungen zählen auch bei Hunden zu den häufigsten Todesursachen: 25 % aller Hunde über 2 Jahre und 45 % aller Hunde über 10 Jahre sterben an Krebs. Viele Hundebesitzer werden also im Laufe ihres Lebens vor die Frage gestellt: Unterziehe ich mein Tier einer Strahlentherapie oder nicht? Überwiegen die Vorteile die möglichen Nebenwirkungen und wie beeinflusst die Therapie die Lebensqualität meines Hundes?
Erfolgreiche Behandlung eines mukokutanen Pemphigoids bei einem jungen Hund
Authors: Udraite Vovk Laura , Klinger Christoph J. , Böhm Teresa M. S. A. , Gedon Natalie K. Y. , Bettenay Sonya V. , Mueller Ralf. S. 
Published: October 2019

ZusammenfassungBei einem 2,5-jährigen, männlich-intakten Foxhound-Beagle-Mischling mit akuter, multifokaler, langsam fortschreitender, erosiv-ulzerierender Dermatitis ohne Juckreiz wurde basierend auf klinischen Symptomen und histologischer Untersuchung von Hautbioptaten ein mukokutanes Pemphigoid diagnostiziert. Betroffen waren Nasenspiegel, Augenlider und Schnauze. Bläschen fanden sich auch an Ohreninnenseiten, Maulschleimhaut und Zunge. Der Patient sprach nicht auf eine immunsuppressive Therapie mit Prednisolon an. Mit oraler Gabe von Doxycyclin und Niacinamid ließ sich eine vollständige Remission erreichen und die Erkrankung blieb unter langfristiger ausschließlicher Therapie mit Niacinamid in Remission.