bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Modulation of Sirtuins by Oxidative Stress
Authors: Santos Leonardo , Escande Carlos , Denicola Ana
Published: December 2015

Sirtuins are a conserved family of NAD‐dependent protein deacylases. Initially proposed as histone deacetylases, it is now known that they act on a variety of proteins including transcription factors and metabolic enzymes, having a key role in the regulation of cellular homeostasis. Seven isoforms are identified in mammals (SIRT1–7), all of them sharing a conserved catalytic core and showing differential subcellular localization and activities. Oxidative stress can affect the activity of sirtuins at different levels: expression, posttranslational modifications, protein‐protein interactions, and NAD levels. Mild oxidative stress induces the expression of sirtuins as a compensatory mechanism, while harsh or prolonged oxidant conditions result in dysfunctional modified sirtuins more prone to degradation by the proteasome. Oxidative posttranslational modifications have been identified in vitro and in vivo, in particular cysteine oxidation and tyrosine nitration. In addition, oxidative stress can alter the interaction with other proteins, like SIRT1 with its protein inhibitor DBC1 resulting in a net increase of deacetylase activity. In the same way, manipulation of cellular NAD levels by pharmacological inhibition of other NAD‐consuming enzymes results in activation of SIRT1 and protection against obesity‐related pathologies. Nevertheless, further research is needed to establish the molecular mechanisms of redox regulation of sirtuins to further design adequate pharmacological interventions.
Mass Effect Alone May Not Explain Pulmonary Vascular Pathology in Severe Congenital Diaphragmatic Hernia
Authors: Derderian Sarkis Christopher , Jayme Christine M. , Cheng Lily S. , Keller Roberta L. , Moon-Grady Anita J. , MacKenzie Tippi C.
Published: December 2015

Congenital diaphragmatic hernia (CDH) and congenital pulmonary airway malformation (CPAM) are diseases in which chest-occupying lesions can result in severe pulmonary hypoplasia. However, significant postnatal mortality due to pulmonary hypertension (PH) is more often seen in patients with CDH. We analyzed prenatal echocardiographic parameters of pulmonary vascular pathology in these groups to understand whether PH in patients with CDH is secondary to a mass effect or to underlying disease. We analyzed pre- and postnatal characteristics of 26 patients with severe CDH and 23 patients with severe CPAM from 2009 to 2012. Severe mediastinal compression, indicated by a low cardiothoracic ratio, was evident in both groups. However, fetuses with severe CDH had smaller pulmonary arteries bilaterally and higher pulsatility indices in the ipsilateral lung than those with severe CPAM. Prenatal modified McGoon indices were significantly lower in patients with CDH versus CPAM. Consistent with these prenatal measurements, postnatal PH was seen more frequently in patients with CDH compared to CPAM. Patients with severe CDH have prenatal evidence of pulmonary vascular remodeling compared to patients with severe CPAM. These results suggest a multifactorial origin for PH in CDH and support the idea of using prenatal medical therapies to promote vascular remodeling in these patients.
Fucoxanthin Induced Suicidal Death of Human Erythrocytes
Authors: Briglia Marilena , Calabró Salvatrice , Signoretto Elena , Alzoubi Kousi , Laufer Stefan , Faggio Caterina , Lang Florian
Published: December 2015

Background/Aims: Fucoxanthin, a carotenoid isolated from brown seaweeds, induces suicidal death or apoptosis of tumor cells and is thus considered for the treatment or prevention of malignancy. In analogy to apoptosis of nucleated cell, erythrocytes may enter eryptosis, the suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress and activation of p38 kinase or protein kinase C. The present study explored, whether and how fucoxanthin induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and abundance of reactive oxygen species (ROS) from DCFDA dependent fluorescence and lipid peroxidation using BODIPY fluoresence. Results: A 48 hours exposure of human erythrocytes to fucoxanthin significantly increased the percentage of annexin-V-binding cells (≥ 50 µM), significantly decreased average forward scatter (≥ 25 µM), significantly increased hemolysis (≥ 25 µM), significantly increased Fluo3-fluorescence (≥ 50 µM), significantly increased lipid peroxidation, but did not significantly modify DCFDA fluorescence. The effect of fucoxanthin on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+, and was insensitive to p38 kinase inhibitor skepinone (2 µM) and to protein kinase C inhibitor calphostin (100 nM). Conclusion: Fucoxanthin triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part due to stimulation of Ca2+ entry.
Regulation of Voltage Gated K+ Channel KCNE1/KCNQ1 by the Janus Kinase JAK3
Authors: Warsi Jamshed , Abousaab Abeer , Fezai Myriam , Elvira Bernat , Lang Florian
Published: December 2015

Background/Aims: Janus kinase 3 (JAK3), a kinase mainly expressed in hematopoietic cells, has been shown to down-regulate the Na+/K+ ATPase and participate in the regulation of several ion channels and carriers. Channels expressed in thymus and regulating the abundance of T lymphocytes include the voltage gated K+ channel KCNE1/KCNQ1. The present study explored whether JAK3 contributes to the regulation of KCNE1/KCNQ1. Methods: cRNA encoding KCNE1/KCNQ1 was injected into Xenopus oocytes with or without additional injection of cRNA encoding wild-type JAK3, constitutively active A568VJAK3, or inactive K851AJAK3. Voltage gated K+ channel activity was measured utilizing two electrode voltage clamp. Results: KCNE1/KCNQ1 activity was significantly increased by wild-type JAK3 and A568VJAK3, but not by K851AJAK3. The difference between oocytes expressing KCNE1/KCNQ1 alone and oocytes expressing KCNE1/KCNQ1 with A568VJAK3 was virtually abrogated by JAK3 inhibitor WHI-P154 (22 µM) but not by inhibition of transcription with actinomycin D (50 nM). Inhibition of KCNE1/KCNQ1 protein insertion into the cell membrane by brefeldin A (5 µM) resulted in a decline of the voltage gated current, which was similar in the absence and presence of A568VJAK3, suggesting that A568VJAK3 did not accelerate KCNE1/KCNQ1 protein retrieval from the cell membrane. Conclusion: JAK3 contributes to the regulation of membrane KCNE1/KCNQ1 activity, an effect sensitive to JAK3 inhibitor WHI-P154.
Macrophage Infiltration into the Glomeruli in Lipoprotein Glomerulopathy
Authors: Takasaki Satoshi , Maeda Kunihiko , Joh Kensuke , Yamakage Shu , Fukase Sachiko , Takahashi Toshiyuki , Suzuki Masayuki , Matsunaga Akira , Saito Takao
Published: December 2015

Lipoprotein glomerulopathy (LPG) is characterized by histopathological features showing intra-glomerular lipoprotein thrombi and type III hyperlipoproteinemia (HLP), with heterozygote mutation of apolipoprotein (apo) E gene. On the other hand, as another renal lipidosis with type III HLP, apoE2 homozygote-related glomerulopathy (apoE2-GN) showing foamy macrophages has been reported. The case of a 25-year-old man who had LPG by clinical behavior and gene analysis, but demonstrated atypical histopathological features with a substantial amount of foamy macrophage infiltration in the glomeruli, is presented. The combination of alleles for apoE Tokyo/Maebashi and classical apoE2 (Arg158Cys) was inferred to be the leading cause of the unique renal pathology with lipoprotein thrombi and foamy macrophages. In addition, foamy macrophages infiltrated some part of the apoE-positive region within the glomerulus, but did not exist in lipoprotein thrombi despite apoE positivity, suggesting that properties of apoE are crucial in the development of LPG rather than macrophage function. This case provides important information related to the pathogenesis of LPG and apoE2-GN.
UGT1A1*28 Genotypes and Respiratory Disease in Very Preterm Infants: A Cohort Study
Authors: Petersen Jesper Padkær , Ebbesen Finn , Hollegaard Mads Vilhelm , Andersson Sofia , Hougaard David Michael , Thorlacius-Ussing Ole , Henriksen Tine Brink
Published: December 2015

Background: Respiratory disease in the very preterm infant is frequent and often severe. Bilirubin is both a potent neurotoxin and antioxidant, and may have a clinical impact on preterm respiratory disease. The Gilbert genotype, the UGT1A1*28 allele, is the major known genetic cause of variation in bilirubin. Objectives: To study the association between respiratory disease in the very preterm infant and the UGT1A1*28 allele. Methods: This is a cohort study of 1,354 very preterm infants (gestational age <32 weeks) born in Jutland, Denmark in 1997-2011. Genotypes were obtained from the Danish Neonatal Screening Biobank, and clinical information was obtained from the databases of two tertiary neonatal intensive care units. Outcomes were the need for surfactant therapy, any need for and duration of supplementary oxygen and bronchopulmonary dysplasia (BPD). Results: Per UGT1A1*28 allele, odds were increased for any need of supplementary oxygen (odds ratio 1.26; 1.05-1.50) and for BPD (odds ratio 1.71; 1.23-2.39), the need of supplementary oxygen increased by 6.38 days (1.87-10.89), and chance per day of no longer needing supplementary oxygen was reduced (hazard rate 0.84; 0.76-0.93). No effect was observed for need of surfactant treatment (odds ratio 1.08; 0.91-1.28). Hardy-Weinberg equilibrium was unlikely for the cohort (p < 0.012). This could be explained by death prior to genotype sampling. In tests of robustness this failed to explain the primary results. Conclusions: Compared to the common genotype, UGT1A1*28 genotypes were associated with an increased need of oxygen supplementation and risk of BPD in very preterm newborns.
Dietary Vitamin A and Visceral Adiposity: A Modulating Role of the Retinol-Binding Protein 4 Gene
Authors: Goodwin Katie , Abrahamowicz Michal , Leonard Gabriel , Perron Michel , Richer Louis , Veillette Suzanne , Gaudet Daniel , Paus Tomas , Pausova Zdenka
Published: December 2015

Background/Aims: Visceral fat (VF) compared with subcutaneous fat (SF) is more closely associated with cardiometabolic disease. Dietary vitamin A (retinol) may reduce adiposity through its effects on adipogenesis differentially in VF and SF, and this effect may be modulated by retinol-binding protein-4 (RBP4). We investigated whether intake of vitamin A is associated with either VF or SF, and whether this association is moderated by the RBP4 genotype (rs10882272, C/T) previously associated with circulating retinol levels. Methods: This was a cross-sectional association study in a sample of 947 adolescents from a French-Canadian founder population. VF and SF were quantified with magnetic resonance imaging, and vitamin A intake was assessed with a 24-hour food recall. All participants were genotyped to determine their RBP4 variant. Results: Dietary intake of vitamin A was negatively associated with VF; however, it was not associated with SF. These relationships were independent of age, sex, height and energy intake, and were modulated by the RBP4 variant. The T allele promoted adiposity-reducing effects of vitamin A in VF and adiposity-enhancing effects in SF, while the C allele had adiposity-reducing effects in both VF and SF. Conclusions: Dietary vitamin A may reduce abdominal adiposity and promote visceral to subcutaneous body fat redistribution during adolescence in an RBP4-dependent manner. These observational findings provide the basis for future interventional studies, which together with genetic information may inject further causality in the association between dietary vitamin A intake and abdominal adiposity.
Restorative Outcomes of a Minimally Invasive Restorative Approach Based on Atraumatic Restorative Treatment to Manage Early Childhood Caries: A Randomised Controlled Trial
Authors: Arrow Peter
Published: December 2015

A pragmatic randomised controlled trial comparing a minimally invasive approach based on atraumatic restorative treatment (ART) procedures (test) was tested against the standard-care approach (control) to treat early childhood caries (ECC) in a primary-care setting in Perth, W.A., Australia. Parent/child dyads with ECC were allocated to the test or control group using stratified block randomisation. Children were examined at baseline and follow-up by two calibrated examiners blinded to group allocation status. Dental therapists trained in ART provided treatment to the test group and dentists treated the control group. Restoration quality was evaluated at follow-up using the ART criteria. Data were analysed on an intention-to-treat basis; test of proportions, Wilcoxon rank test and logistic regression, controlling for clustering of teeth, were used. Two hundred and fifty-four children were randomised (test = 127 and control = 127). There was no statistically significant difference in age, sex and baseline caries experience between the test and control groups. At follow-up (mean interval 11.4 months, SD 3.1), 220 children were examined (test = 115 and control = 105) and 597 teeth (test = 417 and control = 180) were evaluated for restoration quality, of which 16.8% (test) and 6.7% (control) were judged to have failed (required replacement; p < 0.01). Intention-to-treat, multiple logistic regression found multisurface restorations (OR = 10.4) had significantly higher odds of failure, while referral for specialist paediatric care had significantly lower odds of restoration failure (OR = 0.2). The ART-based approach enabled more children and teeth to be treated, and multisurface restoration and treatment in a primary-care setting had higher odds of restoration failure.
Some Important Milestones in the Field of Blood Clotting
Authors: Doolittle Russell F.
Published: December 2015

Several different kinds of ‘milestone' in the field of blood coagulation are described from the middle decades of the 20th century. Although viewed from the standpoint of clotting per se, attention is also given to implications for innate immunity. The first milestone considered is the protracted saga of clotting dependence on vitamin K, an adventure that spanned more than five decades beginning in the 1920s. The second has to do with the discovery of a half-dozen ‘new' clotting factors during the period immediately following World War II. A third pursues a narrower focus and examines the once mysterious transformation of fibrinogen into fibrin. Finally, the clinical treatment of classical hemophilia had a remarkable turning point in the 1960s as the result of simple but sensible measures.
Intraventricular Extension of Supratentorial Intracerebral Hemorrhage: The Modified Graeb Scale Improves Outcome Prediction in Lund Stroke Register
Authors: Hansen Björn M. , Morgan Timothy C. , Betz Joshua F. , Sundgren Pia C. , Norrving Bo , Hanley Daniel F. , Lindgren Arne
Published: December 2015

Background/Aims: The modified Graeb Scale (mGS) is a semi-quantitative method to assess the extension of intraventricular hemorrhage (IVH) in patients with intracerebral hemorrhage (ICH). The mGS has been shown to prognosticate outcome after ICH in cohorts derived from convenience samples. We evaluated the external validity of mGS in supratentorial ICH-patients from an unselected cohort. Methods: ICH-patients were included prospectively and consecutively in Lund Stroke Register. Follow-up survival status was obtained from the National Census Office; functional outcome was obtained from the Swedish Stroke Register or medical records. Using multivariate analyses, we examined if mGS was related to 30-day survival or poor functional outcome (modified Rankin Scale ≥4) at 90 days. Results: Of 198 supratentorial ICH-patients, 86 (43%) had IVH (median mGS 12, range 1-28). In multivariate regression analyses, the mGS independently predicted 30-day mortality (per point; OR 1.16; 95% CI 1.06-1.27; p = 0.002) and poor functional outcome (OR 1.11; 95% CI 1.02-1.20; p = 0.011) after ICH. In receiver-operator characteristic analysis, the addition of mGS tended to be associated with a higher prognostic accuracy for survival (area under curve 0.886 vs. not including mGS 0.812; p = 0.053). Conclusions: The mGS improves outcome prediction after supratentorial ICH beyond other previously established factors in an unselected population.
Takereana, a new genus of Idoteidae (Crustacea: Isopoda: Valvifera) from New Zealand
Authors: POORE GARY C. B. , HURLEY DESMOND E.
Published: December 2015

Takereana n. gen. is erected for the New Zealand species, Idotea festiva Chilton, 1885, which is redescribed. Takereana, Austridotea Poore, 2001 and Idotea Fabricius, 1798 are the only idoteid genera in which both pleonites 1 and 2 are truly articulating. In all other genera of Idoteidae pleonite 2 is variously fused to pleonite 1 and visible only laterally. The new genus differs from Austridotea in that maxillipedal palp articles 2–3 and 4–5 are fused and operculate whereas in Austridotea the palp is of five free articles or has only articles 4–5 fused. All species of Austridotea are smooth with laterally expanded coxae, a quite different habitus from ornamented Takereana festiva. Takereana differs from Idotea in having two uropodal rami rather than one, greater fusion of maxillipedal palp articles, lacking spiniform setae on the pereopods, and unusual narrow pleopods 1. Takereana has an obsolete setose mandibular molar while it is columnar and toothed in both these genera.
Systematic review of diplommatinid land snails (Caenogastropoda, Diplommatinidae) endemic to the Palau Islands. (3) Description of eight new species and two new subspecies of Hungerfordia
Authors: YAMAZAKI MIDORI , YAMAZAKI KAZUNORI , RUNDELL REBECCA, J. , UESHIMA REI
Published: December 2015

Hungerfordia Beddome, 1889 is a land snail genus of the family Diplommatinidae, which shows extensive endemic radiation in the Palau (Belau) islands. Although 42 species or subspecies of the genus have been named to date, many species remain to be described. In this article, we describe ten new taxa of the genus: H. goniobasis exserta subsp. nov., H. ngereamensis sp. nov., H. spiroperculata sp. nov., H. fragilipennis sp. nov., H. brachyptera sp. nov., H. elegantissima anomphala subsp. nov., H. nodulosa sp. nov., H. irregularis sp. nov., H. chilorhytis sp. nov., H. globosa sp. nov.
Two new species of Sycorax (Diptera: Psychodidae: Sycoracinae) from the Oriental Region
Authors: Ježek Jan , Wahab Rodzay Abdul , Ševčík Jan , Wahab Rodzay Abdul , Ševčík Jan
Published: December 2015

Two new species of Sycorax Haliday in Curtis, 1839 are described from Ulu Temburong National Park in Brunei Darussalam: Sycorax konopiki sp. nov. and S. tomkineana sp. nov. Both species were found resting on two frog species: Ansonia leptopus (Günther, 1872) and A. longidigita Inger, 1960. Differential diagnoses for males are included and morphological characters illustrated. Possible host associations of the new species are briefly discussed. DNA barcode sequence (COI) for Sycorax konopiki sp. nov. is also provided.
New replacement name for the species Scarabaeus (Scarabaeolus) nitidus Davis & Deschodt, 2015 (Coleoptera: Scarabaeidae: Scarabaeinae)—not an American pest
Authors: DAVIS ADRIAN L.V. , STALS RIAAN , DESCHODT CHRISTIAN M.
Published: December 2015

In their review of the subgenus Scarabaeus (Scarabaeolus) Balthasar, 1965 (Coleoptera: Scarabaeidae: Scarabaeinae), Deschodt et al. (2015) described seven new species from Africa. One of these was Scarabaeus (Scarabaeolus) nitidus Davis & Deschodt, known by only twelve specimens from Botswana. This new name is preoccupied by Scarabaeus nitidus Linnaeus, 1758, a fact that was overlooked. The latter species has been known as Cotinis nitida (Linnaeus) since Burmeister (1842) placed the species in his new genus Cotinis. It belongs to the subfamily Cetoniinae of Scarabaeidae, is called the Green June Beetle, and is a common pest species throughout most of the eastern United States (Goodrich 1966; Woodruff 2008).
Redescription of Eidophasia syenitella (Herrich-Schaffer, [1854]) (Lepidoptera, Plutellidae)
Authors: BARANIAK EDWARD , SOHN JAE-CHEON
Published: December 2015

The Holarctic genus Eidophasia Stephens, 1842 belongs to Plutellidae (Kyrki 1984, 1990; Dugdale et al. 1999). The genus currently includes 12 species (Sohn & Baraniak in press) which are heterogeneous in morphologies. In fact, there have been no convincing synapomorphies proposed for Eidophasia. Eidophasia syenitella (Herrich-Schäffer, [1854]) is one of the European congeners. Herrich-Schäffer (1853–1855) associated E. syenitella with E. messingiella (Fisher von Röslerstamm, 1840), based two superficial similarities, i.e. a slim body and the presence of scale tuft on the 2nd segment of the labial palpus. Friese (1966) synonymized E. concinnella Christoph, 1888 and E. zukowskyi Amsel, 1939 under E. syenitella. After examining various local populations of E. syenitella from Europe, we found Friese’s synonymy unwarranted. Eidophasia syenitella has been characterized with only its external appearance. There is yet no description of the genitalia available for the species. This gives a challenge in evaluating the taxonomic status of E. syenitella and its two putative synonyms. This issue needs further attention and will be scrutinized in separate papers. Little is known about the biology of E. syenitella. The known larval host records suggest that this species is exclusively associated with a genus of Brassicaceae, Arabis or rockcress. The aim of this paper is to re-describe the species with the genitalia of both sexes for the first time.
Tyneside Neighbourhoods
Authors: Nettle Daniel
Published: December 2015

Nettle’s book presents the results of five years of comparative ethnographic fieldwork in two different neighbourhoods of the same British city, Newcastle upon Tyne. The neighbourhoods are only a few kilometres apart, yet whilst one is relatively affluent, the other is amongst the most economically deprived in the UK. Tyneside Neighbourhoods uses multiple research methods to explore social relationships and social behaviour, attempting to understand whether the experience of deprivation fosters social solidarity, or undermines it. The book is distinctive in its development of novel quantitative methods for ethnography: systematic social observation, economic games, household surveys, crime statistics, and field experiments. Nettle analyses these findings in the context of the cultural, psychological and economic consequences of economic deprivation, and of the ethical difficulties of representing a deprived community. In so doing the book sheds light on one of the main issues of our time: the roles of culture and of socioeconomic factors in determining patterns of human social behaviour.

Tyneside Neighbourhoods is a must read for scholars, students, individual readers, charities and government departments seeking insight into the social consequences of deprivation and inequality in the West.

Nettle’s book presents the results of five years of comparative ethnographic fieldwork in two different neighbourhoods of the same British city, Newcastle upon Tyne. The neighbourhoods are only a few kilometres apart, yet whilst one is relatively affluent, the other is amongst the most economically deprived in the UK. Tyneside Neighbourhoods uses multiple research methods to explore social relationships and social behaviour, attempting to understand whether the experience of deprivation fosters social solidarity, or undermines it. The book is distinctive in its development of novel quantitative methods for ethnography: systematic social observation, economic games, household surveys, crime statistics, and field experiments. Nettle analyses these findings in the context of the cultural, psychological and economic consequences of economic deprivation, and of the ethical difficulties of representing a deprived community. In so doing the book sheds light on one of the main issues of our time: the roles of culture and of socioeconomic factors in determining patterns of human social behaviour. Tyneside Neighbourhoods is a must read for scholars, students, individual readers, charities and government departments seeking insight into the social consequences of deprivation and inequality in the West.
Structural and Environmental Characteristics of Extratropical Cyclones that Cause Tornado Outbreaks in the Warm Sector: A Composite Study
Authors: Tochimoto Eigo , Niino Hiroshi
Published: December 2015

The structural and environmental characteristics of extratropical cyclones that cause tornado outbreaks [outbreak cyclones (OCs)] and that do not [nonoutbreak cyclones (NOCs)] are examined using the Japanese 55-year Reanalysis dataset (JRA-55). Composite analyses show differences between OCs and NOCs: for OCs, storm relative environmental helicity (SREH) and convective available potential energy (CAPE) are notably larger, and the areas in which these parameters have significant values are wider in the warm sector than they are for NOCs. The larger CAPE in OCs is due to larger amounts of low-level water vapor, while the greater SREH is due to stronger low-level southerly wind.

The composite analyses for environmental fields defined by 20-day means suggest that environmental meridional flows have the potential to advect large amounts of warm and moist air northward, creating atmospheric instability in the troposphere that contributes to the occurrence of a tornado outbreak. A piecewise potential vorticity (PV) diagnosis shows that low- to midlevel PV anomalies are the main contributor to the difference in the low-level winds between OCs and NOCs, whereas upper-level PV anomalies make only a minor contribution.

An examination of the structures of the extratropical cyclones and the upper-level jet stream suggests that the difference in the low-level winds between OCs and NOCs is due to differences in the structure of the jet stream. The OCs develop when the jet stream displays larger anticyclonic shear. This causes a more meridionally elongated structure of OCs, resulting in stronger low-level winds in the southeastern quadrant of the cyclones.
Topographic and Boundary Influences on the 22 May 2014 Duanesburg, New York, Tornadic Supercell
Authors: Tang Brian , Vaughan Matthew , Lazear Ross , Corbosiero Kristen , Bosart Lance , Wasula Thomas , Lee Ian , Lipton Kevin
Published: December 2015

The 22 May 2014 Duanesburg, New York, supercell produced an enhanced Fujita scale category 3 (EF3) tornado and 10-cm-diameter hail. The synoptic setup for the event was ambiguous compared to other documented cases of Northeast tornadoes. Mesoscale inhomogeneities due to terrain and baroclinic boundaries played a key role in the evolution and severity of the storm. The storm initiated at the intersection of an outflow boundary and a north–south-oriented baroclinic boundary. The mesocyclone was able to sustain itself as a result of sufficiently large amounts of low-level streamwise vorticity near the boundary despite subcritical values of 0–6-km vertical wind shear. Differential heating across the north–south-oriented boundary strengthened the pressure gradient across it. Strengthening ageostrophic flow across the boundary induced greater upslope flow along the southeastern slope of the Adirondack Mountains and induced terrain channeling up the Mohawk River valley. The channeling led to a maximum in moisture flux convergence and instability in the Mohawk valley. As the supercell moved into the Mohawk valley, radar and lightning data indicated a rapid intensification of the storm. Cold temperatures aloft due to the presence of an elevated mixed layer (EML) coincided with the surface instability to yield a local environment in the Mohawk valley favorable for extremely large hail. As the storm crossed the boundary, large values of 0–1-km wind shear, streamwise vorticity, and low lifting condensation levels combined to create a local environment favorable for tornadogenesis.
Devil Facial Tumor Disease
Authors: Pye R. J. , Woods G. M. , Kreiss A.
Published: December 2015

Devil facial tumor disease (DFTD) is an emergent transmissible cancer exclusive to Tasmanian devils ( Sarcophilus harrisii) and threatening the species with extinction in the wild. Research on DFTD began 10 years ago, when nothing was known about the tumor and little about the devils. The depth of knowledge gained since then is impressive, with research having addressed significant aspects of the disease and the devils’ responses to it. These include the cause and pathogenesis of DFTD, the immune response of the devils and the immune evasion mechanisms of the tumor, the transmission patterns of DFTD, and the impacts of DFTD on the ecosystem. This review aims to collate this information and put it into the context of conservation strategies designed to mitigate the impacts of DFTD on the devil and the Tasmanian ecosystem.
APLP1 as a cerebrospinal fluid biomarker for γ-secretase modulator treatment
Authors: Sjödin Simon , Andersson Kerstin K. A. , Mercken Marc , Zetterberg Henrik , Borghys Herman , Blennow Kaj , Portelius Erik
Published: December 2015

Introduction

Alzheimer’s disease brains are characterized by extracellular plaques containing the aggregated amyloid β42 (Aβ42) peptide and intraneuronal tangles containing hyperphosphorylated tau. Aβ42 is produced by sequential processing of the amyloid precursor protein (APP) by β-secretase followed by γ-secretase. Substantial efforts have been put into developing pharmaceuticals preventing the production or increasing the clearance of Aβ42. However, treatments inhibiting γ-secretase have proven disappointing due to off-target effects. To circumvent these effects, γ-secretase modulators (GSMs) have been developed, which rather than inhibiting γ-secretase shift its preference into producing less aggregation-prone shorter Aβ peptides. Belonging to the same family of proteins as APP, amyloid-like protein 1 (APLP1) is also a substrate for γ-secretase. Herein we investigated whether the GSM E2012 affects APLP1 processing in the central nervous system by measuring APLP1 peptide levels in cerebrospinal fluid (CSF) before and after E2012 treatment in dogs.

Methods

An in-house monoclonal APLP1 antibody, AP1, was produced and utilized for immunopurification of APLP1 from human and dog CSF in a hybrid immuno-affinity mass spectrometric method. Seven dogs received a single dose of 20 or 80 mg/kg of E2012 in a randomized cross-over design and CSF was collected prior to and 4, 8 and 24 hours after dosing.

Results

We have identified 14 CSF APLP1 peptides in humans and 12 CSF APLP1 peptides in dogs. Of these, seven were reproducibly detectable in dogs who received E2012. We found a dose-dependent relative increase of the CSF peptides APLP1β17, 1β18 and 1β28 accompanied with a decrease of 1β25 and 1β27 in response to E2012 treatment. All peptides reverted to baseline over the time of sample collection.

Conclusion

We show an in vivo effect of the GSM E2012 on the processing of APLP1 which is measurable in CSF. These data suggest that APLP1 peptides may be used as biomarkers to monitor drug effects of GSMs on γ-secretase processing in clinical trials. However, this requires further investigation in larger cohorts, including studies in man.
Neurogranin and YKL-40: independent markers of synaptic degeneration and neuroinflammation in Alzheimer’s disease
Authors: Hellwig Konstantin , Kvartsberg Hlin , Portelius Erik , Andreasson Ulf , Oberstein Timo Jan , Lewczuk Piotr , Blennow Kaj , Kornhuber Johannes , Maler Juan Manuel , Zetterberg Henrik , Spitzer Philipp
Published: December 2015

Introduction

Neuroinflammation and synaptic degeneration are major neuropathological hallmarks in Alzheimer’s disease (AD). Neurogranin and YKL-40 in cerebrospinal fluid (CSF) are newly discovered markers indicating synaptic damage and microglial activation, respectively.

Methods

CSF samples from 95 individuals including 39 patients with AD dementia (AD-D), 13 with mild cognitive impairment (MCI) due to AD (MCI-AD), 29 with MCI not due to AD (MCI-o) and 14 patients with non-AD dementias (non-AD-D) were analyzed for neurogranin and YKL-40.

Results

Patients with dementia or MCI due to AD showed elevated levels of CSF neurogranin (p < 0.001 for AD-D and p < 0.05 for MCI-AD) and YKL-40 (p < 0.05 for AD-D and p = 0.15 for MCI-AD) compared to mildly cognitively impaired subjects not diagnosed with AD. CSF levels of neurogranin and YKL-40 did not differ between MCI not due to AD and non-AD dementias. In AD subjects no correlation between YKL-40 and neurogranin was found. The CSF neurogranin levels correlated moderately with tau and p-tau but not with Aβ42 or the MMSE in AD samples. No relevant associations between YKL-40 and MMSE or the core AD biomarkers, Aβ42, t-tau and p-tau were found in AD subjects.

Conclusions

Neurogranin and YKL-40 are promising AD biomarkers, independent of and complementary to the established core AD biomarkers, reflecting additional pathological changes in the course of AD.
Protocol for a randomised, double‐blind, placebo‐controlled study of grass allergen immunotherapy tablet for seasonal allergic rhinitis: time course of nasal, cutaneous and immunological outcomes
Authors: Steveling Esther Helen , Lao‐Araya Mongkol , Koulias Christopher , Scadding Guy , Eifan Aarif , James Louisa K. , Dumitru Alina , Penagos Martin , Calderón Moisés , Andersen Peter Sejer , Shamji Mohamed , Durham Stephen R.
Published: December 2015

Background

Seasonal Allergic Rhinitis is characterised by inflammation of the nasal mucosa upon exposure to common aeroallergens, affecting up to 20–25 % of the population. For those patients whose symptoms are not controlled by standard medical treatment, allergen specific immunotherapy is a therapeutic alternative. Although several studies have shown changes in immunologic responses as well as long term tolerance following treatment with a sublingual allergy immunotherapy tablet, a detailed time course of the early mechanistic changes of local and systemic T and B cell responses and the effects on B cell repertoire in the nasal mucosa have not been fully examined.

Methods/design

This is a randomized, double‐blind, single‐centre, placebo controlled, two arm time course study based in the United Kingdom comparing sublingual allergy immunotherapy tablet (GRAZAX®, ALK‐Abello Horsholm, Denmark) plus standard treatment with placebo plus standard treatment. Up to 50 moderate to severe grass pollen allergic participants will be enrolled to ensure randomisation of at least 44. Further, we shall enrol 20 non‐atopic volunteers. Screening will be completed before eligible atopic participants are randomised to one of the two treatment arms in a 1 to 1 ratio. The primary endpoint will be the total nasal symptom score assessed over 60 min following grass pollen nasal allergen challenge after 12 months of treatment. Clinical assessments and/or mechanistic analyses on blood, nasal fluid, brushing and biopsies will be performed at baseline at 1, 2, 3, 4 (coinciding with the peak pollen season), 6 and 12 months of treatment. After 12 months of treatment, unblinding will take place. Those atopic participants receiving active treatment will continue therapy for another 12 months followed by a post treatment phase of 12 months. Assessments and collection of biologic samples from these participants will take place again at 24 and at 36 months from the start of treatment. The 20 healthy, non‐atopic controls will undergo screening and one visit only coinciding with the 12 month visit for the atopic participants.

Discussion

The trial will end in April 2017. The trial is registered with ClinicalTrials.gov and the trial identifying number is NCT02005627.

Trial registration: Primary Registry: ClinicalTrials.gov, Trial Identifying number: NCT02005627, Secondary identifying numbers: EudraCT number: 2013‐003732‐72 REC: 13/EM/0351, Imperial College London (Sponsor): 13IC0847, Protocol Version 6.0, Date: 16.05.2014
Hybrid de novo genome assembly of the Chinese herbal plant danshen (Salvia miltiorrhiza Bunge)
Authors: Zhang Guanghui , Tian Yang , Zhang Jing , Shu Liping , Yang Shengchao , Wang Wen , Sheng Jun , Dong Yang , Chen Wei
Published: December 2015

Background

Danshen (Salvia miltiorrhiza Bunge), also known as Chinese red sage, is a member of Lamiaceae family. It is valued in traditional Chinese medicine, primarily for the treatment of cardiovascular and cerebrovascular diseases. Because of its pharmacological potential, ongoing research aims to identify novel bioactive compounds in danshen, and their biosynthetic pathways. To date, only expressed sequence tag (EST) and RNA-seq data for this herbal plant are available to the public. We therefore propose that the construction of a reference genome for danshen will help elucidate the biosynthetic pathways of important secondary metabolites, thereby advancing the investigation of novel drugs from this plant.

Findings

We assembled the highly heterozygous danshen genome with the help of 395 × raw read coverage using Illumina technologies and about 10 × raw read coverage by using single molecular sequencing technology. The final draft genome is approximately 641 Mb, with a contig N50 size of 82.8 kb and a scaffold N50 size of 1.2 Mb. Further analyses predicted 34,598 protein-coding genes and 1,644 unique gene families in the danshen genome.

Conclusions

The draft danshen genome will provide a valuable resource for the investigation of novel bioactive compounds in this Chinese herb.
Intermittent Fasting Promotes Fat Loss With Lean Mass Retention, Increased Hypothalamic Norepinephrine Content, and Increased Neuropeptide Y Gene Expression in Diet-Induced Obese Male Mice
Authors: Gotthardt Juliet D. , Verpeut Jessica L. , Yeomans Bryn L. , Yang Jennifer A. , Yasrebi Ali , Roepke Troy A. , Bello Nicholas T.
Published: December 2015

Clinical studies indicate alternate-day, intermittent fasting (IMF) protocols result in meaningful weight loss in obese individuals. To further understand the mechanisms sustaining weight loss by IMF, we investigated the metabolic and neural alterations of IMF in obese mice. Male C57/BL6 mice were fed a high-fat diet (HFD; 45% fat) ad libitum for 8 weeks to promote an obese phenotype. Mice were divided into four groups and either maintained on ad libitum HFD, received alternate-day access to HFD (IMF-HFD), and switched to ad libitum low-fat diet (LFD; 10% fat) or received IMF of LFD (IMF-LFD). After 4 weeks, IMF-HFD (∼13%) and IMF-LFD (∼18%) had significantly lower body weights than the HFD. Body fat was also lower (∼40%–52%) in all diet interventions. Lean mass was increased in the IMF-LFD (∼12%–13%) compared with the HFD and IMF-HFD groups. Oral glucose tolerance area under the curve was lower in the IMF-HFD (∼50%), whereas the insulin tolerance area under the curve was reduced in all diet interventions (∼22%–42%). HPLC measurements of hypothalamic tissue homogenates indicated higher (∼55%–60%) norepinephrine (NE) content in the anterior regions of the medial hypothalamus of IMF compared with the ad libitum-fed groups, whereas NE content was higher (∼19%–32%) in posterior regions in the IMF-LFD group only. Relative gene expression of Npy in the arcuate nucleus was increased (∼65%–75%) in IMF groups. Our novel findings indicate that intermittent fasting produces alterations in hypothalamic NE and neuropeptide Y, suggesting the counterregulatory processes of short-term weight loss are associated with an IMF dietary strategy.
A pH-Controlled Reversible Phase Transfer and Electrolytic Size-Fractionation of Stable Silver Nanoparticles Capped with a Long Amino Amide Dicarboxylic Acid
Authors: Delbecq Frederic , Yamano Itsuki , Kawai Takeshi
Published: December 2015

The synthesis of a long alkylaminoamide dicarboxylic acid amphoteric species has been achieved. Employed as capping agent, the reduction of ionic silver in water led to the formation of small (10–100 nm) and hydrophobic diacid bilayer coated silver nanoparticles (AgNPs). In a biphasic system (e.g. H2O–CHCl3), a pH-controlled and reversible phase transfer phenomenon was observed. At different stages, the formation of these nanoparticles was studied by UV–vis spectroscopy, their stability was controlled by zeta-potential measurement and both shape and morphology were observed by transmission electron microscopy (TEM). The ionic strength of the AgNPs was tested by the addition of inorganic salt electrolyte (NaCl, CaCl2). A NaCl concentration dependant size fractionation of the AgNPs between the same above biphasic system was also studied by means of analytical techniques such as dynamic light scattering (DLS), TEM, and UV–vis spectroscopy.
Typification of the Indo‐Pacific Sirophysalis trinodis (Fucales: Sargassaceae)
Authors: Boisset Fernando , Ferrer-Gallego P. Pablo
Published: December 2015

The typification of the Indo‐Pacific seaweed Sirophysalis trinodis (Phaeophyceae) is discussed. Original material conserved in the Herbarium Forsskålii at C is designated as the lectotype.
Sincerity in Corporate Philanthropy, Stakeholder Perceptions and Firm Value
Authors: Cuypers Ilya R. P. , Koh Ping-Sheng , Wang Heli
Published: December 2015

This study extends the literature on symbolic management by incorporating the role of stakeholder perceptions into the context of corporate philanthropy. In particular, we differentiate between the quantitative (generous giving) and qualitative (innovative giving) aspects of giving. We argue that although stakeholders may perceive both types of giving as being substantive rather than symbolic, innovative giving is likely to be perceived as more substantive than generous giving is and, thus, has a greater impact on firm value. Furthermore, stakeholder perceptions of corporate philanthropy as being more symbolic or substantive are influenced by firm characteristics—the type of products or services that a firm provides and the life-cycle stage that the firm is in—which provide stakeholders with a context to better assess the nature of a firm’s philanthropic actions and the substantiveness of its giving. We find support for our predictions using a sample covering U.S. firms’ philanthropic activities over a 19-year period.
Quality and value in the NHS hospital: challenges and evolving solutions
Authors: Tibrewal Sheo B
Published: December 2015

Measuring quality in NHS hospitals—and its integration with value for continuous improvement of patient care and efficiency—remains a daunting challenge despite various efforts and reports. Three key issues that need urgent attention are highlighted, namely the lack of: an agreed lean set of quality metrics that are widely accepted and practised; a robust and reliable method of data collection; and a common language to communicate with all stakeholders. A literature review on quality issues is presented together with possible solutions, as a basis for a further collaborative pilot study with all stakeholders—including patients—to develop a set of agreed solutions and tools for wider adoption and practise in NHS hospitals.
The influence of workload levels on performance in a rural hospital
Authors: Asamani James Avoka , Amertil Ninon P , Chebere Margaret
Published: December 2015

The importance of workload on staff performance has been widely acknowledged, but opinions are divided as to what level of workload is desirable for optimum staff performance. Previously, researchers have attempted to demonstrate the impact of workload on the individual staff, organisation and the consumer. However, gaps and uncertainties in the literature also confirm the need for further investigation of the perceived workload levels of staff, the factors influencing workload levels and the contextual relationship between workload and staff performance. A quantitative descriptive survey was undertaken to elicit the perceived workload levels of health workers in the Donkorkrom Presbyterian Hospital, Ghana, and how it is perceived to impact on staff performance. One hundred clinical and non-clinical staff were selected for the study. The study found that workload level of health workers was perceived as moderate (2.91 ± 0.541 on a five-point Likert scale). However, nurses/midwives were perceived to have the highest workload, followed by paramedics, support staff and doctors. Work interruptions, procedures and processes involved in treating patients, as well as facing work-related uncertainties, were identified as determinants of perceived workload among health workers. Results show that 75% of health workers perceived moderate workload assignment would increase their performance. It is recommended that health institutions review and improve organisational procedures and processes to ensure smooth workflow and eliminate or minimise work interruptions that unnecessarily compound workload and undermines performance.
Das Wort Gottes und die Ökumene
Authors: Weinrich Michael
Published: December 2015

Although Karl Barth showed some reservations especially against the Geneva ecumenism, by his theology of God’s word he established a contribution to an ecumenical perspective which has actually not yet been taken up. God’s word has to remain God’s word. The church cannot dispose freely of God’s word but remains in need of being addressed time and again by this word. It is a fundamental part of the liberty of the church to stay first and foremost open towards God’s word. Consequently, the efforts devoted to the survival of the church have to be redirected to a concentration on a timely actualization of its mission. The church has to bear witness not to itself but to the »sound of the Easter morning« perceivable even today. The unity of the church, characterized by reciprocal diversity, becomes an incidental by-product of its vital focus on God’s word.
Re-präsentation und Übersetzung als zentrale Aufgaben einer Öffentlichen Theologie und Religionspädagogik
Authors: Pirner Manfred L.
Published: December 2015

The social-philosophical discussion about the role of religion in late modern society opens up new perspectives for a public theology in general and a public religious pedagogy in specific. This contribution develops some of these perspectives referencing primarily Jürgen Habermas’ proposal to understand secularization as a common complementary process of learning of religious and non-religious people, in which translation gains central relevance. The consequences for religious pedagogy include the foundation as well as the conceptualization and impact of public religious learning.
Imago Dei
Authors: Kunstmann Joachim
Published: December 2015

Theological anthropology determines the human being as image of God. He/she is a social being directed towards a counterpart. This is plausible from a psychological perspective as well: the experiences of meaning, happiness, longing and love define the life of the individual in an essential way; these sentiments can be experienced primarily in relation with others or with nature and culture. Based on such existential considerations, religious pedagogy can devote itself to (more) concrete questions and human experiences. It is thereby leaving the traditional scheme of given teaching content and addressee behind, which cannot convince any longer and which is neither overcome by elementarization nor by performative religious didactics. Religion is symbolic interpretation of life; therefore religious pedagogy is plausible inasmuch as it takes questions of (the meaning of) life as its start and brings them to a religious interpretation.