bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulatory impact on voluntary climate change–related reporting by Australian government‐owned corporations
Authors: Liu Zihan , Abhayawansa Subhash , Jubb Christine , Perera Luckmika
Published: April 2017

This paper concerns voluntary climate change–related reporting of government‐owned corporations (GOCs). We investigate whether the Australian National Gresenhouse and Energy Reporting Scheme (NGERS), a regulation stipulating the disclosure of greenhouse gas emissions to government, subsequently made publicly available on a Website, has a positive impact on the voluntary disclosure of climate change–related information not required by the regulation. We find that implementation of NGERS has a positive effect on voluntary climate change‐related disclosures by GOCs. Hence, mandating disclosure of organisations’ negative environmental performance, such as greenhouse gas emissions, can influence voluntary disclosures of a broad range of related information particularly in organisations that are not subject to capital markets incentives. However, upon later but concurrent implementation of a Carbon Tax after a highly partisan and divisive political debate, climate change–related disclosures by GOCs reduce, consistent with the de Villiers and van Staden (2006) argument that when disclosures might increase awareness of sensitive issues, avoidance of attention to the issue might be the best strategy to retain legitimacy.
The Propensity to Split and CEO Compensation
Authors: Devos Erik , Elliott William B. , Warr Richard S.
Published: April 2017

We analyze the relation between the delta and vega of a chief executive officer's (CEO) compensation and the propensity of the firm to engage in a split. Controlling for other well‐known factors, we find that CEOs with compensation that has higher levels of delta are more likely to split their shares. Furthermore, the choice of split factor is inversely related to delta. Our results are economically significant: for the average (median) firm in our sample, a stock split results in a CEO wealth gain of $4.9 million ($84,000).
Calcium Isotopic Fractionation and Compositions of Geochemical Reference Materials
Authors: Liu Fang , Zhu Hong L. , Li Xin , Wang Gui Q. , Zhang Zhao F.
Published: April 2017

High‐precision calcium isotopic compositions of a set of geological reference materials from the IAG (OU‐6), ANRT (UB‐N), MPI‐DING, USGS and GSJ, relative to NIST SRM 915a, are reported here. Measurements were performed by thermal ionisation mass spectrometry (Triton instrument) using a 42Ca–43Ca double spike. δ44/40Ca values of selected reference materials, mainly felsic rocks, are reported for the first time. Felsic rock values of δ44/40Ca ranged from 0.13‰ to 1.17‰, probably implying Ca isotopic fractionation could occur during magma evolution. δ44/40Ca values of ultramafic rocks, ranging from 0.74‰ to 1.51‰, were positively correlated with MgO and negatively with CaO contents, possibly owing to Ca isotopic fractionation during partial melting. δ44/40Ca of intermediate‐mafic rocks were around 0.78‰ and displayed limited variation, suggesting Ca isotopic fractionation is insignificant during magma evolution processes. As expected, δ44/40Ca of sedimentary and metamorphic rocks varied widely due to complex geological processes.
Aging‐dependent expression of synapse‐related proteins in the mouse brain
Authors: Shiotani Hajime , Maruo Tomohiko , Sakakibara Shotaro , Miyata Muneaki , Mandai Kenji , Mochizuki Hideki , Takai Yoshimi
Published: April 2017

A synapse is a cell adhesion structure that permits a neuron to pass a chemical or electrical signal to another neuron. They connect neurons and form neural networks that are essential for brain functions, such as learning and memory. At a chemical synapse, the presynapse and the postsynapse are connected by cell adhesion molecules. The presynapse contains synaptic vesicles and their release machinery, whereas the postsynapse contains postsynaptic densities and receptors for the neurotransmitters. Many proteins constituting a synapse have been identified, but their life‐span expression profiles remain elusive. Here, we investigated the expression levels of representative synapse‐related proteins by Western blot using the extranuclear supernatant fraction of the brains of mice at various ages. These proteins were classified into seven groups depending on their expression profiles during the embryonic stage, those from postnatal day 6 (P6) to P30, and those after P90. The expression levels of the majority of the proteins were gradually increased from the embryonic stage and then decreased at P14 or P30. After P90, the expression levels were not markedly changed or, in some proteins, increased. These results indicate that the expression levels of the synapse‐related proteins are regulated orderly in an aging‐dependent manner.
The effect of ageing on changes in myofibrillar protein in selected muscles in relation to the tenderness of meat obtained from cross‐breed heifers
Authors: Moczkowska Małgorzata , Półtorak Andrzej , Wierzbicka Agnieszka
Published: April 2017

The aim of this study was to evaluate the impact of the ageing on changes in selected myofibrillar proteins and Warner–Bratzler shear force values in muscles from cross‐breed Charolaise × Holstein Friesian heifers. Triceps brachii (TB), infraspinatus (IS), vastus lateralis (VL), semimembranosus (SM), biceps femoris (BF) and semitendinous (ST) muscles after ageing were examined. A significant muscle effect was found in the case of basic chemical composition, Warner–Bratzler shear force values and cooking loss. The vastus lateralis characterised by the lowest intramuscular fat percentage (P ≤ 0.05). The highest connective tissue content was shown for infraspinatus. This muscle had the lowest Warner–Bratzler shear force values in every ageing time, regardless of the cooking method. Throughout the ageing process, selected myofibrillar proteins were altered in all examined muscles, but at varying rates. The SDS‐PAGE electrophoresis and Western blotting analysis showed that desmin and troponin‐T degradation affected both muscles and ageing effects (P ≤ 0.001).
The genomic potential of the Aspirin in Reducing Events in the Elderly and Statins in Reducing Events in the Elderly studies
Authors: Lacaze Paul , Woods Robyn , Zoungas Sophia , McNeil John ,   on behalf of the ASPREE Investigator Group,   ASPREE Healthy Ageing Biobank,   and the STAREE Investigator Group
Published: April 2017

Human genetic studies are continuing to increase in size and scale, but the availability of well‐phenotyped longitudinal cohorts remains rare. Significant infrastructure, investment and effort are required to establish and maintain high‐quality cohorts with biobanking, genetic consent and repeated clinical data measurements. Australia currently has two such cohorts established by Monash University as part of community‐based clinical trials in the elderly. Both studies involve capture of demographic, mood, cognitive performance, physical function, neuroimaging, audiometry and various clinical data types over an average of 5 years. The ASPirin in Reducing Events in the Elderly (ASPREE) cohort is comprised of 16 703 Australians aged over 70 years and 2411 Americans aged over 65 years – recruited and randomised to either daily low‐dose aspirin or placebo to examine the preventative benefit of aspirin on a range of clinical outcomes. The STAtins in Reducing Events in the Elderly (STAREE) study uses a similar model, and is currently recruiting 10 000 men and women aged over 70 years across Australia randomised to either low‐dose statins or placebo. Both cohorts involve biobanking and consent for genetic research, with recruitment through a network of general practitioners in the community. A combination of whole‐genome and targeted sequencing approaches will allow gene–phenotype relationships to be explored within the context of detailed longitudinal data. Genetic risk factors for late‐onset high‐burden conditions, such as cardiovascular disease and dementia will be investigated, plus research into other areas, such as healthy ageing and disease resilience will be possible due to unique phenotypes of health.
Hepatitis A to E: what's new?
Authors: Mohsen Waled , Levy Miriam T.
Published: April 2017

Viral hepatitis contributes to significant morbidity and mortality worldwide. While acute infection may be self‐limiting, unrecognised chronic infection and under‐utilisation of guideline‐based approaches to therapy contribute to increasing rates of cirrhosis, hepatocellular carcinoma and death. Our aim was to review the current evidence for screening, diagnosis and treatment in hepatitis A to E. Evidence for this review was sourced from international and Australian guidelines and high‐quality clinical trials. MEDLINE was searched using structured key word strategy and retrieved articles were reviewed methodically to inform a brief and up‐to‐date synopsis of hepatitis A to E. We share some of the recent developments in viral hepatitis, specifically the new therapies for hepatitis C. Direct‐acting antiviral therapies are safe, well‐tolerated and effective. Subsidies allow access for all Australians with most strains of hepatitis C. We outline evidence underpinning efficacy and safety of treatment for hepatitis B, while clarifying some of the nuances in the setting of pregnancy and immunosuppression. We provide a simplified concept to facilitate understanding of the five phases of hepatitis B; practical for real‐world setting. Hepatitis A to E is a broad topic, not all aspects of these viruses can be covered in this short review. We provided suggestions for evidence based guidelines, which are a suitable supplement to this article.
Neue systemische Antimykotika: Wirkungsmechanismen, Interaktionen, unerwünschte Wirkungen
Authors: Schäfer‐Korting Monika
Published: April 2017

Der Zunahme systemischer Pilzinfektionen und der Resistenzsteigerung bei Antimykotika ist durch Neuentwicklungen bei diesen Antiinfektiva zu begegnen. Mit den Azolen der 2. Generation, die hochpotente Inhibitoren der Ergosterolsynthese sind, und einem partialsynthetischen Echinocandin, einem Hemmstoff des Enzyms Glucansynthase, stehen nunmehr neue stark wirksame Vertreter für die Behandlung der invasiven Aspergillose zur Verfügung. Als Arzneimittel zugelassen sind Voriconazol bzw. Caspofungin, möglicherweise eignen sich diese bei Beachtung der Kontraindikationen und ‐ bei Voriconazol ‐ möglicher Wechselwirkungen gut verträglichen Arzneistoffe auch für die Therapie anderer schwerwiegender Mykosen, z. B. systemischer und oropharyngealer Candidosen bei Immundefizienz.
Frühe Beschreibung einer pulmonalen Aspergillose 1847 aus Greifswald
Authors: Knoke M. , Bernhardt Hannelore , Schwesinger G.
Published: April 2017

Im Jahre 1847 hat der Greifswalder Medizinstudent Theodor Sluyter (1817–1895) in seiner in Berlin veröffentlichten Inauguraldissertation den ersten sicher bestimmbaren Fall einer Lungenaspergillose beim Menschen beschrieben. 1856 ordnete Rudolf Virchow (1821–1902) an Hand der beigegebenen Zeichnung den Pilz der Gattung Aspergillus zu. Der Obduzent war möglicherweise Carl Ferdinand Eichstedt (1816 bis 1892), der 1846 als erster einen Pilz als Ursache der Pityriasis versicolor angesehen hatte. Weitere beteiligte Greifswalder Wissenschaftler waren Wilhelm Baum (1799 bis 1883), Theodor Litzmann (1815–1890) und der Botaniker Johann Konrad Schauer (1813–1848), deren Lebensläufe ebenso wie der von T. Sluyter dargestellt werden.
The role of formal support in the lives of children of mothers with intellectual disability
Authors: Collings Susan , Grace Rebekah , Llewellyn Gwynnyth
Published: April 2017

Background

Mothers with intellectual disability face socioeconomic disadvantage and social isolation, which is associated with poorer child outcomes. Social services feature prominently in the lives of mothers with intellectual disability especially those without informal support; however, the role of formal support in the lives of their children has not been explored.

Methods

Seven children aged 7–11 years took part in semi‐structured interviews to explore their social experiences. Stories about interactions at home, school and with peers were analysed to illuminate influences, including social support, in their lives.

Results

Formal support can provide an enduring relationship for children from socially restricted homes when it focuses on the child's abilities, interests and needs as distinct from those of their mother. Child‐focused support can be from a paid worker or volunteer.

Conclusions

Family support services need to apply a child focus to improve the well‐being of children in vulnerable families.
A nurse‐led education and cognitive behaviour therapy‐based intervention among adults with uncontrolled type 2 diabetes: A randomised controlled trial
Authors: Whitehead Lisa C. , Crowe Marie T. , Carter Janet D. , Maskill Virginia R. , Carlyle Dave , Bugge Carol , Frampton Chris M. A.
Published: April 2017

Rationale, aims and objectives

Diabetes mellitus is associated with significant morbidity, mortality, and escalating health care costs. Research has consistently demonstrated the importance of glycaemic control in delaying the onset, and decreasing the incidence, of both the short‐term and long‐term complications of diabetes. Although glycaemic control is difficult to achieve and challenging to maintain, it is key to reducing negative disease outcomes.

The aim of this study was to determine whether a nurse‐led educational intervention alone or a nurse‐led intervention using education and acceptance and commitment therapy (ACT) was effective in reducing hemoglobin A1c (HbA1c) in people living with uncontrolled type 2 diabetes compared to usual care.

Methods

Adults over the age of 18 years, with a confirmed diagnosis of type 2 diabetes and HbA1c outside of the recommended range (4%‐7%, 20‐53 mmol/mol) for 12 months or more, were eligible to participate. Participants were randomised to either a nurse‐led education intervention, a nurse‐led education plus ACT intervention, or a usual care. One hundred and eighteen participants completed baseline data collection (N = 34 education group, N = 39 education plus ACT, N = 45 control group). An intention to treat analysis was used.

Results

A statistically significant reduction in HbA1c in the education intervention group was found (P = .011 [7.48, 8.14]). At 6 months, HbA1c was reduced in both intervention groups (education group −0.21 and education and ACT group −0.04) and increased in the control group (+0.32). A positive change in HbA1c (HbA1c reduced) was noted in 50 participants overall. Twice as many participants in the intervention groups demonstrated an improvement as compared to the control group (56% of the education group, 51% education plus ACT, and 24% control group.

Conclusions

At 6 months post intervention, HbA1c was reduced in both intervention groups with a greater reduction noted in the nurse‐led education intervention.
Is sporadic Alzheimer′s disease a developmental disorder?
Authors: Arendt Thomas , Stieler Jens , Ueberham Uwe
Published: April 2017

Alzheimer′s disease (AD) is a neurodegenerative disorder of higher age that specifically occurs in human. Its clinical phase, characterized by a decline in physiological, psychological, and social functioning, is preceded by a long clinically silent phase of at least several decades that might perhaps even start very early in life. Overall, key functional abilities in AD patients decline in reverse order of the development of these abilities during normal childhood and adolescence. Early symptoms of AD, thus, typically affect mental functions that have been acquired only during very recent hominid evolution and as such are specific to human. Neurofibrillar degeneration, a typical neuropathological lesion of the disease and one of the most robust pathological correlates of cognitive impairment, is rarely seen in non‐primate mammals and even non‐human primates hardly develop a pathology comparable to those seen in AD patients. Neurofibrillar degeneration is not randomly distributed throughout the AD brain. It preferentially affects brain areas that become increasingly predominant during the evolutionary process of encephalization. During progression of the disease, it affects cortical areas in a stereotypic sequence that inversely recapitulates ontogenetic brain development. The specific distribution of cortical pathology in AD, moreover, appears to be determined by the modular organization of the cerebral cortex which basically is a structural reflection of its ontogeny. Here, we summarize recent evidence that phylogenetic and ontogenetic dimensions of brain structure and function provide the key to our understanding of AD. More recent molecular biological studies of the potential pathogenetic role of a genomic mosaic in the brains of patients with AD might even provide arguments for a developmental origin of AD.

This article is part of a series “Beyond Amyloid”.

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Interactions between integrase inhibitors and human arginase 1
Authors: Lisi Lucia , Pizzoferrato Michela , Miscioscia Fabiola Teresa , Topai Alessandra , Navarra Pierluigi
Published: April 2017

The neuro‐pathogenic mechanism(s) underlying HIV‐associated neurocognitive disorders are mostly unknown. HIV‐infected macrophages and microglial cells play a crucial role and the metabolic fate of l‐arginine may be highly relevant to microglia activation. In this context, arginase (ARG), which uses l‐arginine as substrate, can be on the same time a target and source of oxidative stress and inflammation. In this study, we investigated whether integrase strand transfer inhibitors share with the other antiretroviral drugs the ability to inhibit ARG activity. We used the previously validated cell model, namely the human microglia cell line, as well as the computational chemistry approach. Furthermore, here we characterized the activity of purified human ARG in a cell‐free in vitro system, and investigated the effects of integrase strand transfer inhibitors in this newly validated model. Overall evidence shows that Dolutegravir, Raltegravir and Elvitegravir inhibit ARG activity.

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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

The 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.

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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

The 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

The 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

With 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

Aim

Optimal 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.

Methods

We 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.

Results

A 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.

Conclusion

A 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

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.

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

The 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

Pyroptosis 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 Objective

Aggregatibacter 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 Methods

We 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.

Results

Whereas 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.

Conclusion

We 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

Sleep 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

Coral 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

The 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

Cognitive 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.
The Reflecting Brain: Reflection Competence in an Educational Setting Is Associated With Increased Electroencephalogram Activity in the Alpha Band
Authors: Rominger Christian , Reitinger Johannes , Seyfried Clemens , Schneckenleitner Eva , Fink Andreas
Published: April 2017

Teachers' ability to critically reflect classroom situations in relation to their own actions constitutes an important prerequisite to improve teaching performance and professional behavior. This study investigated electroencephalogram activity in the alpha band during a reflection task before and after training in a sample of preservice teachers. Reflection was associated with stable brain activity patterns over two separate time points of assessment. Increased alpha power during reflection of pedagogically relevant scenarios was found at occipital sites, especially in participants with higher reflection competence. This is consistent with prior studies that showed increased alpha power during mental imagery among other tasks. Training of reflection competence, administered in a subsample of participants, was accompanied by increased reflection performance, while no intervention‐related effects were found at the neurophysiological level. The findings of this study provide first preliminary evidence of increased alpha power at occipital sites as a neurophysiological indicator of reflections of pedagogically relevant educational scenarios.
Basal subarachnoid hemorrhage by rupture of arteriovenous malformation at the cerebellopontine angle
Authors: Takayama Mio , Kashiwagi Masayuki , Hara Kenji , Matsusue Aya , Waters Brian , Ikematsu Natsuki , Kubo Shin‐ichi
Published: April 2017

A man in his late forties had lived as a recluse for more than ten years. He was found dead in his room. At autopsy, subarachnoid hemorrhage (SAH) was detected at the base of the brain, which weighed 1333 g. The cerebellar tonsil was swollen. The cerebral ventricle was enlarged and filled with blood. A hematoma was observed in the upper part of the left side of the cerebellar hemisphere. The location and size of SAH in this case indicated that the rupture of a cerebral aneurysm (CA) had occurred; however, CA was not detected. A mass of blood vessels buried in the hematoma was observed at the left cerebellopontine angle (CPA). The vascular lesion showed round‐shaped blood vessels as well as flat‐shaped vessels with the appearance of veins, but with elastic fibers indicative of arteries. The lesion was considered to be the nidus and was 5–8 mm in size. Feeding arteries appeared to be from the anterior inferior cerebellar artery (AICA). However, the draining vein and anastomotic parts of the artery and vein were not confirmed. Based on these histopathological features, this vascular lesion was diagnosed as arteriovenous malformation (AVM). A differential diagnosis between AVM at CPA and CA is needed in order to identify the source of non‐traumatic SAH.
The Physcomitrella patens exocyst subunit EXO70.3d has distinct roles in growth and development, and is essential for completion of the moss life cycle
Authors: Rawat Anamika , Brejšková Lucie , Hála Michal , Cvrčková Fatima , Žárský Viktor
Published: April 2017

The exocyst, an evolutionarily conserved secretory vesicle‐tethering complex, spatially controls exocytosis and membrane turnover in fungi, metazoans and plants. The exocyst subunit EXO70 exists in multiple paralogs in land plants, forming three conserved clades with assumed distinct roles. Here we report functional analysis of the first moss exocyst subunit to be studied, Physcomitrella patens PpEXO70.3d (Pp1s97_91V6), from the, as yet, poorly characterized EXO70.3 clade.

Following phylogenetic analysis to confirm the presence of three ancestral land plant EXO70 clades outside angiosperms, we prepared and phenotypically characterized loss‐of‐function Ppexo70.3d mutants and localized PpEXO70.3d in vivo using green fluorescent protein‐tagged protein expression.

Disruption of PpEXO70.3d caused pleiotropic cell elongation and differentiation defects in protonemata, altered response towards exogenous auxin, increased endogenous IAA concentrations, along with defects in bud and gametophore development. During mid‐archegonia development, an abnormal egg cell is formed and subsequently collapses, resulting in mutant sterility. Mutants exhibited altered cell wall and cuticle deposition, as well as compromised cytokinesis, consistent with the protein localization to the cell plate.

Despite some functional redundancy allowing survival of moss lacking PpEXO70.3d, this subunit has an essential role in the moss life cycle, indicating sub‐functionalization within the moss EXO70 family.
Using traits to uncover tropical forest function
Authors: McDowell Nate G. , Xu Chonggang
Published: April 2017

This article is a Commentary on Asner et al. (pp. 973–988), Bahar et al. (pp. 1002–1018), Chavana‐Bryant et al. (pp. 1049–1063), Goldsmith et al. (pp. 989–1001), Malhi et al. (pp. 1019–1032), Rowland et al. (pp. 1064–1077) and Wu et al. (pp. 1033–1048), all of which are published in this issue.
What predicts first date success? A longitudinal study of modality switching in online dating
Authors: SHARABI LIESEL L. , CAUGHLIN JOHN P.
Published: April 2017

This study uses a longitudinal design to investigate the effects of online dating sites on first date success. Participants were surveyed before their first date with someone from an online dating site (N = 186) and again after meeting their partner in person (N = 94). As part of the survey, they also supplied the e‐mails they had sent to their partner through the dating site so their actual communication could be examined. Findings indicated that first date success was predictable from features of participants' online impressions and relational dynamics. The results are discussed in terms of their theoretical and methodological contributions to the literature on relationship development, as well as their practical implications for online dating sites and users.
Very small pediatric donor kidney transplantation in pediatric recipients
Authors: Yaffe H. C. , Friedmann P. , Kayler L. K.
Published: April 2017

Kidneys from very small pediatric donors (age <5 years, weight <21 kg) may be a means to increase the donor pool for pediatric recipients. Transplantation of small pediatric kidneys is more commonly performed in adult recipients due to the increased risks of technical complications, thrombosis, and early graft failure. While these risks are abrogated in adult recipients by limiting the donor weight to ≥10 kg and using the EB technique, it is unknown whether pediatric recipients achieve comparable results. US national data were assessed for all first‐time, deceased‐donor, kidney‐only pediatric recipients, 1/1996‐10/2013, who received very small pediatric donor grafts or grafts from ideal adult donors. We identified 57 pediatric EB, 110 pediatric SK, and 2350 adult transplants. The primary outcome was 3‐year all‐cause graft survival. Kaplan‐Meier curves showed worse outcomes for pediatric grafts compared to adult ideal grafts (P=.042). On multivariate analysis, pediatric recipients of SK grafts had significantly higher HRs (aHR 2.01, 95% CI 1.34‐3.00) and pediatric recipients of EB grafts had somewhat higher non‐significant HRs (1.57; 95% CI 0.88‐2.79) for graft survival. These results suggest cautionary use of very small pediatric donors as a source to expand the donor pool for pediatric candidates.