bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isogenic blood–brain barrier models based on patient‐derived stem cells display inter‐individual differences in cell maturation and functionality
Authors: Patel Ronak , Page Shyanne , Al‐Ahmad Abraham Jacob 
Published: April 2017

AbstractThe blood–brain barrier (BBB) constitutes an important component of the neurovascular unit formed by specialized brain microvascular endothelial cells (BMECs) surrounded by astrocytes, pericytes, and neurons. Recently, isogenic in vitro models of the BBB based on human pluripotent stem cells have been documented, yet the impact of inter‐individual variability on the yield and phenotype of such models remains to be documented. In this study, we investigated the impact of inter‐individual variability on the yield and phenotype of isogenic models of the BBB, using patient‐derived induced pluripotent stem cells (iPSCs). Astrocytes, BMECs, and neurons were differentiated from four asymptomatic patient‐derived iPSCs (two males, two females). We differentiated such cells using existing differentiation protocols and quantified expression of cell lineage markers, as well as BBB phenotype, barrier induction, and formation of neurite processes. iPSC‐derived BMECs showed barrier properties better than hCMEC/D3 monolayers; however, we noted differences in the expression and activity among iPSC lines. In addition, we noted differences in the differentiation efficiency of these cells into neural stem cells and progenitor cells (as noted by differences in expression of cell lineage markers). Such differences were reflected later in the terminal differentiation, as seen as ability to induce barrier function and to form neurite processes. Although we demonstrated our ability to obtain an isogenic model of the BBB with different patients’ iPSCs, we also noted subtle differences in the expression of cell lineage markers and cell maturation processes, suggesting the presence of inter‐individual polymorphisms.image
Uterine remodelling during pregnancy and pseudopregnancy in the brushtail possum (Trichosurus vulpecula; Phalangeridae)
Authors: Laird Melanie K. , McShea Hanon , McAllan Bronwyn M. , Murphy Christopher R. , Thompson Michael B. 
Published: April 2017

AbstractThe formation of a placenta is critical for successful mammalian pregnancy and requires remodelling of the uterine epithelium. In eutherian mammals, remodelling involves specific morphological changes that often correlate with the mode of embryonic attachment. Given the differences between marsupial and eutherian placentae, formation of a marsupial placenta may involve patterns of uterine remodelling that are different from those in eutherians. Here we present a detailed morphological study of the uterus of the brushtail possum (Trichosurus vulpecula; Phalangeridae) throughout pregnancy, using both scanning and transmission electron microscopy, to identify whether uterine changes in marsupials correlate with mode of embryonic attachment as they do in eutherian mammals. The uterine remodelling of T. vulpecula is similar to that of eutherian mammals with the same mode of embryonic attachment (non‐invasive, epitheliochorial placentation). The morphological similarities include development of large apical projections, and a decrease in the diffusion distance for haemotrophes around the period of embryonic attachment. Importantly, remodelling of the uterus in T. vulpecula during pregnancy differs from that of a marsupial species with non‐invasive attachment (Macropus eugenii; Macropodidae) but is similar to that of a marsupial with invasive attachment (Monodelphis domestica; Didelphidae). We conclude that modes of embryonic attachment may not be typified by a particular suite of uterine changes in marsupials, as is the case for eutherian mammals, and that uterine remodelling may instead reflect phylogenetic relationships between marsupial lineages.
The association between wedging of the aorta and cardiac structural anatomy as revealed using multidetector‐row computed tomography
Authors: Mori Shumpei , Anderson Robert H. , Takaya Tomofumi , Toba Takayoshi , Ito Tatsuro , Fujiwara Sei , Watanabe Yoshiaki , Nishii Tatsuya , Kono Atsushi K. , Hirata Ken‐ichi 
Published: April 2017

AbstractThe aortic root is wedged within the cardiac base. The precise extent of aortic wedging, however, and its influence on the surrounding cardiac structures, has not been systematically investigated. We analysed 100 consecutive patients, who underwent coronary arterial computed tomographic angiography. We assessed the extent of aortic wedging by measuring the vertical distance between the non‐adjacent aortic sinus and the inferior epicardium. A shorter distance indicates deeper aortic wedging. We assessed the tilt angle and diameter of the ascending aorta, the relative heights of the left atrial roof and the oval fossa, the shape of the proximal right coronary artery, the angle of the aorta relative to the left ventricular axis, and the lung volume. The mean extent of wedging was 42.7 ± 9.8 mm. Multivariate analysis revealed that ageing, male gender, increased body mass index, patients without cardiomyopathy, the extent of tilting and dilation of the ascending aorta, and lung volume were all independent predictors for deeper aortic wedging (R2 = 0.7400, P < 0.0001). The extent of wedging was additionally correlated with a relatively high left atrial roof (R2 = 0.1394, P < 0.0001) and oval fossa (R2 = 0.1713, P < 0.0001), the shepherd's crook shape of the proximal right coronary artery (R2 = 0.2376, P < 0.0001), and the narrowness of the angulation of the root relative to the left ventricular axis (R2 = 0.2544, P < 0.0001). In conclusion, ageing, male gender, obesity, background cardiac disease, aortic tilting and dilation, and lung volume are all correlated with the extent of wedging of the aortic root within the cardiac base.
Esthetic Rehabilitation of Retained Primary Teeth—A Conservative Approach
Authors: Parise Gré Cristina , Schweigert Bona Vitor , Pedrollo Lise Diogo , Monteiro Júnior Sylvio 
Published: April 2017

AbstractWith the advancement in ceramic restorations bonded to tooth structure, the treatment has become a feasible and conservative option to restore teeth with alteration in shape when owing to high demand in esthetics, with or without minimum tooth preparation. This article describes a report of a 32‐year‐old woman who was dissatisfied with her smile. The patient reported that she still had deciduous teeth, and that the maxillary lateral incisors had been restored with direct resin composite to correct the teeth shape. After discussing the restorative possibilities, a decision was made to place all‐ceramic crowns (lithium disilicate glass‐ceramic) with minimal tooth preparation, which figures as a conservative full‐coverage approach. An esthetic outcome resembling a natural‐looking smile resulted in the patient's satisfaction. Bonding of all‐ceramic crowns onto minimally prepared deciduous teeth figures as a conservative treatment in case of partial anodontia, which decreases the chance of root resorption induced by trauma and benefits from good adhesion to enamel.
Seven versus 10 days antibiotic therapy for culture‐proven neonatal sepsis: A randomised controlled trial
Authors: Rohatgi Smriti , Dewan Pooja , Faridi Mohammad Moonis Akbar , Kumar Ashwani , Malhotra Rajeev Kumar , Batra Prerna 
Published: April 2017

AimOptimal duration of parenteral antibiotics for treating neonatal sepsis ranges from 7–14 days. We compared the efficacy of 7 versus 10 days duration of intravenous antibiotics for neonatal septicaemia.MethodsWe randomised blood culture‐proven septic neonates (≥32 weeks and birth weight ≥1.5 kg) to receive either 7 or 10 days duration of intravenous antibiotics. We followed up neonates upto 28 days after stopping antibiotics for treatment failure defined by reappearance of clinical sepsis with a blood culture growing the same organism as cultured earlier, or in the absence of a positive culture, the presence of C‐reactive protein and as adjudicated by an expert committee.ResultsA total of 132 neonates were randomised to receive either 7 (n = 66) or 10 (n = 66) days duration of antibiotic therapy. Out of 128 neonates (64 per group) followed up, two (one per group) were regarded as ‘treatment failure’, and two were labelled as fresh episodes of sepsis (both in 10‐day group). The risk (95% confidence interval) for treatment failure in the 7‐day group was (1.0 (0.064–15.644) was not significantly higher. Neonates in both groups had comparable need for oxygen, inotropic support and blood products, duration of oxygen therapy and time to attainment of full feeds. The duration of hospitalisation was significantly longer in the 10‐day group.ConclusionA 7‐day course of intravenous antibiotics may be sufficient to treat neonatal sepsis with the advantage of shorter hospital stay, but a larger meta‐analysis would be required to state this with a degree of certainty.
Safety issues of compounds acting on adenosinergic signalling
Authors: Schmidt Jan , Ferk Polonca 
Published: April 2017

Abstract

Objectives
Much research has been performed on the field of identifying the roles of adenosine and adenosinergic signalling, but a relatively low number of marketing authorizations have been granted for adenosine receptor (AdR) ligands. In part, this could be related to their safety issues; therefore, our aim was to examine the toxicological and adverse effects data of different compounds acting on adenosinergic signalling, including different AdR ligands and compounds resembling the structure of adenosine. We also wanted to present recent pharmaceutical developments of experimental compounds that showed promising results in clinical trial setting.

Key findings
Safety issues of compounds modulating adenosinergic signalling were investigated, and different mechanisms were presented. Structurally different classes of compounds act on AdRs, the most important being adenosine, adenosine derivatives and other non-nucleoside compounds. Many of them are either not selective enough or are targeting other targets of adenosinergic signalling such as metabolizing enzymes that regulate adenosine levels. Many other targets are also involved that are not part of adenosinergic signalling system such as GABA receptors, different channels, enzymes and others. Some synthetic AdR ligands even showed to be genotoxic.

Summary
Current review presents safety data of adenosine, adenosine derivatives and other non-nucleoside compounds that modulate adenosinergic signalling. We have presented different mechanisms that participate to an adverse effect or toxic outcome. A separate section also deals with possible organ-specific toxic effects on different in-vitro and in-vivo models.
Melatonin protects cardiac microvasculature against ischemia/reperfusion injury via suppression of mitochondrial fission‐VDAC1‐HK2‐mPTP‐mitophagy axis
Authors: Zhou Hao , Zhang Ying , Hu Shunying , Shi Chen , Zhu Pingjun , Ma Qiang , Jin Qinhua , Cao Feng , Tian Feng , Chen Yundai 
Published: April 2017

AbstractThe cardiac microvascular system, which is primarily composed of monolayer endothelial cells, is the site of blood supply and nutrient exchange to cardiomyocytes. However, microvascular ischemia/reperfusion injury (IRI) following percutaneous coronary intervention is a woefully neglected topic, and few strategies are available to reverse such pathologies. Here, we studied the effects of melatonin on microcirculation IRI and elucidated the underlying mechanism. Melatonin markedly reduced infarcted area, improved cardiac function, restored blood flow, and lower microcirculation perfusion defects. Histological analysis showed that cardiac microcirculation endothelial cells (CMEC) in melatonin‐treated mice had an unbroken endothelial barrier, increased endothelial nitric oxide synthase expression, unobstructed lumen, reduced inflammatory cell infiltration, and less endothelial damage. In contrast, AMP‐activated protein kinase α (AMPKα) deficiency abolished the beneficial effects of melatonin on microvasculature. In vitro, IRI activated dynamin‐related protein 1 (Drp1)‐dependent mitochondrial fission, which subsequently induced voltage‐dependent anion channel 1 (VDAC1) oligomerization, hexokinase 2 (HK2) liberation, mitochondrial permeability transition pore (mPTP) opening, PINK1/Parkin upregulation, and ultimately mitophagy‐mediated CMEC death. However, melatonin strengthened CMEC survival via activation of AMPKα, followed by p‐Drp1S616 downregulation and p‐Drp1S37 upregulation, which blunted Drp1‐dependent mitochondrial fission. Suppression of mitochondrial fission by melatonin recovered VDAC1‐HK2 interaction that prevented mPTP opening and PINK1/Parkin activation, eventually blocking mitophagy‐mediated cellular death. In summary, this study confirmed that melatonin protects cardiac microvasculature against IRI. The underlying mechanism may be attributed to the inhibitory effects of melatonin on mitochondrial fission‐VDAC1‐HK2‐mPTP‐mitophagy axis via activation of AMPKα.
Melatonin alleviates inflammasome‐induced pyroptosis through inhibiting NF‐κB/GSDMD signal in mice adipose tissue
Authors: Liu Zhenjiang , Gan Lu , Xu Yatao , Luo Dan , Ren Qian , Wu Song , Sun Chao 
Published: April 2017

AbstractPyroptosis is a proinflammatory form of cell death that is associated with pathogenesis of many chronic inflammatory diseases. Melatonin is substantially reported to possess anti‐inflammatory properties by inhibiting inflammasome activation. However, the effects of melatonin on inflammasome‐induced pyroptosis in adipocytes remain elusive. Here, we demonstrated that melatonin alleviated lipopolysaccharides (LPS)‐induced inflammation and NLRP3 inflammasome formation in mice adipose tissue. The NLRP3 inflammasome‐mediated pyroptosis was also inhibited by melatonin in adipocytes. Further analysis revealed that gasdermin D (GSDMD), the key executioner of pyroptosis, was the target for melatonin inhibition of adipocyte pyroptosis. Importantly, we determined that nuclear factor κB (NF‐κB) signal was required for the GSDMD‐mediated pyroptosis in adipocytes. We also confirmed that melatonin alleviated adipocyte pyroptosis by transcriptional suppression of GSDMD. Moreover, GSDMD physically interacted with interferon regulatory factor 7 (IRF7) and subsequently formed a complex to promote adipocyte pyroptosis. Melatonin also attenuated NLRP3 inflammasome activation and pyroptosis, which was induced by LPS or obesity. In summary, our results demonstrate that melatonin alleviates inflammasome‐induced pyroptosis by blocking NF‐κB/GSDMD signal in mice adipose tissue. Our data reveal a novel function of melatonin on adipocyte pyroptosis, suggesting a new potential therapy for melatonin to prevent and treat obesity caused systemic inflammatory response.
The cagE gene sequence as a diagnostic marker to identify JP2 and non‐JP2 highly leukotoxic Aggregatibacter actinomycetemcomitans serotype b strains
Authors: Johansson A. , Claesson R. , Höglund Åberg C. , Haubek D. , Oscarsson J. 
Published: April 2017

Background and ObjectiveAggregatibacter actinomycetemcomitans is involved in oral and systemic infections, and is associated with, eg aggressive forms of periodontitis and with endocarditis. The cagE gene encodes a ≈39 kDa putative exotoxin expressed by A. actinomycetemcomitans. The level of conservation of cagE, and its possible significance in periodontal disease, has not yet been thoroughly investigated. In the present study, the role of the cagE gene as a diagnostic marker has been investigated.Material and MethodsWe have used conventional polymerase chain reaction (PCR), quantitative PCR and whole genome sequencing data to determine the prevalence of cagE in A. actinomycetemcomitans based on analysis of: (i) 249 isolates, collected and cultivated in a Ghanaian longitudinal cohort study; (ii) a serotype b collection of 19 strains; and (iii) the 36 A. actinomycetemcomitans genomes available in the NCBI database.ResultsWhereas cagE was absent in the other serotypes, our data support that this gene sequence is linked to a virulent and highly leukotoxic group of serotype b strains, including both JP2 and non‐JP2 genotypes of A. actinomycetemcomitans.ConclusionWe propose that cagE has the potential to be used as a PCR‐based gene marker for the identification of a virulent and highly leukotoxic group of serotype b strains, including both JP2 and non‐JP2 genotypes. This finding might be of importance in the risk assessment of the development of periodontal attachment loss in young individuals and hence suggested to be a relevant discovery in future development of new diagnostic tools and/or treatment strategies.
Creatine supplementation reduces sleep need and homeostatic sleep pressure in rats
Authors: Dworak Markus , Kim Tae , Mccarley Robert W. , Basheer Radhika 
Published: April 2017

SummarySleep has been postulated to promote brain energy restoration. It is as yet unknown if increasing the energy availability within the brain reduces sleep need. The guanidine amino acid creatine (Cr) is a well‐known energy booster in cellular energy homeostasis. Oral Cr–monohydrate supplementation (CS) increases exercise performance and has been shown to have substantial effects on cognitive performance, neuroprotection and circadian rhythms. The effect of CS on cellular high‐energy molecules and sleep–wake behaviour is unclear. Here, we examined the sleep–wake behaviour and brain energy metabolism before and after 4‐week‐long oral administration of CS in the rat. CS decreased total sleep time and non‐rapid eye movement (NREM) sleep significantly during the light (inactive) but not during the dark (active) period. NREM sleep and NREM delta activity were decreased significantly in CS rats after 6 h of sleep deprivation. Biochemical analysis of brain energy metabolites showed a tendency to increase in phosphocreatine after CS, while cellular adenosine triphosphate (ATP) level decreased. Microdialysis analysis showed that the sleep deprivation‐induced increase in extracellular adenosine was attenuated after CS. These results suggest that CS reduces sleep need and homeostatic sleep pressure in rats, thereby indicating its potential in the treatment of sleep‐related disorders.
Tropical coral reef coral patterns in Indonesian shallow water areas close to underwater volcanic vents at Minahasa Seashore, and Mahengetang and Gunung Api Islands
Authors: Januar Hedi I. , Zamani Neviaty P. , Soedarma Dedi , Chasanah Ekowati , Wright Anthony D. 
Published: April 2017

AbstractCoral community patterns on some Indonesian reefs influenced by CO2 from underwater volcanic vents and nutrients from eutrophication pressures were examined. The overall aim of the study was to provide an insight into the significance of future ocean acidification compared to eutrophication pressures on tropical coral communities. Coral cover and seawater characteristics at acidified sites (with varied levels of eutrophication), i.e., moderate acidification (pH: 7.87 ± 0.04), low acidification (pH: 8.01 ± 0.04) and reference (pH: 8.2 ± 0.02), were observed at reefs associated with Minahasa Seashore, and Mahengetang and Gunung Api Islands. Results showed that coral community patterns varied among locations and acidified sites, e.g., domination of families such as Alcyoniidae, Acroporidae, Poritidae and Heliporidae, and with different levels of abiotic cover. Surprisingly, pH was not detected as the major determining factor. This finding probably relates to tropical seawater temperatures being high enough to still allow for aragonite deposition even at pH values down to 7.8. Nutrients (phosphate and dissolved inorganic nitrogen) were shown to be the main determining factors that influenced community patterns on the observed coral reefs. Overall, the results indicate that tropical coral reef community patterns will continue to vary as pH decreases to the predicted oceanic value of pH 7.8 over the next 100 years, and bio‐geo‐ecological characteristics and anthropogenic pressures will be the major factors determining Indonesian tropical coral community structure, compared to pH.
Annama H chondrite—Mineralogy, physical properties, cosmic ray exposure, and parent body history
Authors: Kohout Tomáš , Haloda Jakub , Halodová Patricie , Meier Matthias M. M. , Maden Colin , Busemann Henner , Laubenstein Matthias , Caffee Marc. W. , Welten Kees C. , Hopp Jens , Trieloff Mario , Mahajan Ramakant R. , Naik Sekhar , Trigo‐Rodriguez Josep M. , Moyano‐Cambero Carles E. , Oshtrakh Michael I. , Maksimova Alevtina A. , Chukin Andrey V. , Semionkin Vladimir A. , Karabanalov Maksim S. , Felner Israel , Petrova Evgeniya V. , Brusnitsyna Evgeniia V. , Grokhovsky Victor I. , Yakovlev Grigoriy A. , Gritsevich Maria , Lyytinen Esko , Moilanen Jarmo , Kruglikov Nikolai A. , Ishchenko Aleksey V. 
Published: April 2017

AbstractThe fall of the Annama meteorite occurred early morning (local time) on April 19, 2014 on the Kola Peninsula (Russia). Based on mineralogy and physical properties, Annama is a typical H chondrite. It has a high Ar‐Ar age of 4.4 Ga. Its cosmic ray exposure history is atypical as it is not part of the large group of H chondrites with a prominent 7–8 Ma peak in the exposure age histograms. Instead, its exposure age is within uncertainty of a smaller peak at 30 ± 4 Ma. The results from short‐lived radionuclides are compatible with an atmospheric pre‐entry radius of 30–40 cm. However, based on noble gas and cosmogenic radionuclide data, Annama must have been part of a larger body (radius >65 cm) for a large part of its cosmic ray exposure history. The 10Be concentration indicates a recent (3–5 Ma) breakup which may be responsible for the Annama parent body size reduction to 30–35 cm pre‐entry radius.
A Pilot Study of Classroom‐Based Cognitive Skill Instruction: Effects on Cognition and Academic Performance
Authors: Mackey Allyson P. , Park Anne T. , Robinson Sydney T. , Gabrieli John D. E. 
Published: April 2017

ABSTRACTCognitive skills are associated with academic performance, but little is known about how to improve these skills in the classroom. Here, we present the results of a pilot study in which teachers were trained to engage students in cognitive skill practice through playing games. Fifth‐grade students at an experimental charter school were randomly assigned to receive cognitive skill instruction (CSI) or instruction in geography and typing. Students in the CSI group improved significantly more than the control group on a composite measure of cognitive skills. CSI was more effective for students with lower standardized test scores. Although there was no group effect on test scores, cognitive improvement correlated positively with test score improvement only in the CSI group. Beyond showing that cognitive skills can be improved in the classroom, this study provides lessons for the future of CSI, including changes to professional development and challenges for scalability.