bluuebunny/crossref_metadata_2025 huggingface dataset:
Alcohol and Cigarette Smoke Components Activate Human Pancreatic Stellate Cells: Implications for the Progression of Chronic Pancreatitis
Authors: Lee Alexandra T. K. , Xu Zhihong , Pothula Srinivasa P. , Patel Mishaal B. , Pirola Romano C. , Wilson Jeremy S. , Apte Minoti V.
Published: October 2015

Background

Chronic pancreatitis, a known complication of alcohol abuse, is characterized histopathologically by prominent fibrosis. Pancreatic stellate cells (PSCs) are responsible for producing this fibrous tissue in chronic pancreatitis and are activated by alcohol. Progression of alcoholic chronic pancreatitis (as assessed by calcification and fibrosis) is thought to be facilitated by concurrent smoking, but the mechanisms are unknown. This study aimed to (a) determine whether human PSCs (hPSCs) and rat PSCs express nicotinic acetylcholine receptors (nAChRs), which are known to bind 2 important components of cigarette smoke, namely nicotine and nicotine‐derived nitrosamine ketone (NNK), and (b) examine the effects of cigarette smoke components in the presence and absence of alcohol on PSC activation in vitro.

Methods

Western blotting was used to detect the presence of nAChRs in primary cultures of PSCs. Clinically relevant concentrations of cigarette smoke components (either cigarette smoke extract [CSE], NNK, or nicotine) ± ethanol (EtOH) were used to treat primary cultures of PSCs, and stellate cell activation was assessed by cell migration, proliferation, collagen production, and apoptosis.

Results

We demonstrate, for the first time, that PSCs express nAChRs (isoforms α3, α7, β, ε) and that the expression of the α7 isoform in hPSCs is induced by CSE + EtOH. We also provide novel findings that PSCs are activated by CSE and NNK (both alone and in combination with EtOH) as evidenced by an increase in cell migration and/or proliferation. Further, we demonstrate that activation of PSCs by CSE + EtOH and NNK + EtOH may be mediated via nAChRs on the cells.

Conclusions

PSCs are activated by clinically relevant concentrations of cigarette smoke components (CSE and NNK), alone and in combination with EtOH. Thus, in alcoholics who smoke, progression of pancreatic fibrosis may be facilitated by the combined effects of alcohol and cigarette smoke components on hPSC behavior.
Personality and Substance Use: Psychometric Evaluation and Validation of the Substance Use Risk Profile Scale (SURPS) in English, Irish, French, and German Adolescents
Authors: Jurk Sarah , Kuitunen‐Paul Sören , Kroemer Nils B. , Artiges Eric , Banaschewski Tobias , Bokde Arun L. W. , Büchel Christian , Conrod Patricia , Fauth‐Bühler Mira , Flor Herta , Frouin Vincent , Gallinat Jürgen , Garavan Hugh , Heinz Andreas , Mann Karl F. , Nees Frauke , Paus Tomáš , Pausova Zdenka , Poustka Luise , Rietschel Marcella , Schumann Gunter , Struve Maren , Smolka Michael N. ,   the IMAGEN consortium
Published: October 2015

Background

The aim of the present longitudinal study was the psychometric evaluation of the Substance Use Risk Profile Scale (SURPS).

Methods

We analyzed data from N = 2,022 adolescents aged 13 to 15 at baseline assessment and 2 years later (mean interval 2.11 years). Missing data at follow‐up were imputed (N = 522). Psychometric properties of the SURPS were analyzed using confirmatory factor analysis. We examined structural as well as convergent validity with other personality measurements and drinking motives, and predictive validity for substance use at follow‐up.

Results

The hypothesized 4‐factorial structure (i.e., anxiety sensitivity, hopelessness, impulsivity [IMP], and sensation seeking [SS]) based on all 23 items resulted in acceptable fit to empirical data, acceptable internal consistencies, low to moderate test–retest reliability coefficients, as well as evidence for factorial and convergent validity. The proposed factor structure was stable for both males and females and, to lesser degree, across languages. However, only the SS and the IMP subscales of the SURPS predicted substance use outcomes at 16 years of age.

Conclusions

The SURPS is unique in its specific assessment of traits related to substance use disorders as well as the resulting shortened administration time. Test–retest reliability was low to moderate and comparable to other personality scales. However, its relation to future substance use was limited to the SS and IMP subscales, which may be due to the relatively low‐risk substance use pattern in the present sample.
Audit opinions and information asymmetry in the stock market
Authors: Abad David , Sánchez‐Ballesta Juan P. , Yagüe José
Published: October 2015

This study analyses the relationship between the content of the audit reports and information asymmetry levels in the stock market for a sample of Spanish firms. By implementing an association study, we document (1) that firms with audit qualifications show higher information asymmetry levels than those with unqualified opinions; (2) firms with non‐quantified qualifications show higher informational asymmetry than firms with quantified qualifications; and (3) we find a stronger effect on the level of informational asymmetry in the case of going concern qualifications. Our findings suggest that audit qualifications reporting more uncertainty on firm accounting statements result in higher adverse selection risk.
Low testosterone and sexual symptoms in men with acute coronary syndrome can be used to predict major adverse cardiovascular events during long‐term follow‐up
Authors: Chmiel A. , Mizia‐Stec K. , Wierzbicka‐Chmiel J. , Rychlik S. , Muras A. , Mizia M. , Bienkowski J.
Published: October 2015

Low total testosterone (TT) and sexual symptoms are common among men with coronary artery disease, however its impact on major adverse cardiovascular events (MACE) is still debatable. We investigated whether low TT and coexisting sexual symptoms in men with acute coronary syndrome (ACS) can be used to predict the incidence of MACE. In the prospective study 120 consecutive men (mean age 58 ± 9 years; diabetes 27%; current smokers 58%; left ventricular ejection fraction 50 ± 10%) with ACS were included. The group of men with the presence of three sexual symptoms (decreased frequency of morning erections, a lack of sexual thoughts and erectile dysfunction) and with TT serum concentration <3.2 ng/mL was distinguished. All of the patients had their prognosis assessed according to the Global Registry of Acute Coronary Events (GRACE Score 2.0). Primary composite endpoint – MACE (recurrent ischaemia, non‐fatal myocardial infarction, stroke and death) and secondary endpoint – in stent restenosis (ISR) were registered during the 18.3 month follow‐up period. The mean TT level in the entire group was 3.7 ± 0.5 ng/mL. Low TT was diagnosed in 63 (52.5%) men. Both low TT and sexual symptoms were diagnosed in 57 (47%) participants. During the follow‐up, 29 (24.2%) participants experienced MACE, 20 (16.6%) men ISR. In the Cox proportional hazards regression, high risk of death on the GRACE score (HR 3.16; 95% CI: 1.5–6.6; p = 0.002), the presence of low TT and sexual symptoms (HR 2.75; 95% CI: 1.26–6.04; p = 0.02) independently predicted an incidence of a MACE (p = 0.006). For the secondary endpoint only low TT and sexual symptoms (HR 2.68; 95% CI: 1.03–6.94; p = 0.034) were independent covariates which predicted IRS. Low TT which coexists with sexual symptoms in males with ACS can be used to predict MACE, especially IRS independently of classic cardiovascular risk factors.
A PLK4 mutation causing azoospermia in a man with Sertoli cell‐only syndrome
Authors: Miyamoto T. , Bando Y. , Koh E. , Tsujimura A. , Miyagawa Y. , Iijima M. , Namiki M. , Shiina M. , Ogata K. , Matsumoto N. , Sengoku K.
Published: October 2015

About 15% of couples wishing to have children are infertile; approximately half these cases involve a male factor. Polo‐like kinase 4 (PLK‐4) is a member of the polo protein family and a key regulator of centriole duplication. Male mice with a point mutation in the Plk4 gene show azoospermia associated with germ cell loss. Mutational analysis of 81 patients with azoospermia and Sertoli cell‐only syndrome (SCOS) identified one man with a heterozygous 13‐bp deletion in the Ser/Thr kinase domain of PLK4. Division of centrioles occurred in wild‐type PLK4‐transfected cells, but was hampered in PLK‐4‐mutant transfectants, which also showed abnormal nuclei. Thus, this PLK4 mutation might be a cause of human SCOS and nonobstructive azoospermia.
Cost‐effectiveness analysis of sacral nerve stimulation as treatment for severe irritable bowel syndrome
Authors: Tipsmark L. S. , Fassov J. , Lundby L. , Laurberg S. , Ehlers L. , Krogh K.
Published: October 2015

Aim

Early results from sacral nerve stimulation (SNS) for severe irritable bowel syndrome (IBS) are promising but estimates of cost‐effectiveness are lacking. Our object was to perform a cost‐effectiveness analysis forSNSas an alternative to no treatment ofIBS.

Method

This retrospective analysis was based on the results from a randomized controlled crossover study with a cost‐utility analysis performed on patient‐level data and modelling of censored data over a projected period of time of up to 20 years. The analysis was conducted on an intention‐to‐treat approach. For estimation of the uncertainty of the incremental cost‐effectiveness ratio a bias corrected bootstrap analysis was performed.

Results

Cost‐effectiveness was not reached for 4 years after permanent implantation (£31 270 per quality‐adjusted life years), which was the upper limit for patient follow‐up, but our data imply a cost‐effectiveness from a 7‐year perspective onwards.

Conclusion

The study indicates theSNStreatment forIBSis cost effective from a 7‐year perspective onwards.
The Selective Laziness of Reasoning
Authors: Trouche Emmanuel , Johansson Petter , Hall Lars , Mercier Hugo
Published: October 2015

Reasoning research suggests that people use more stringent criteria when they evaluate others' arguments than when they produce arguments themselves. To demonstrate this “selective laziness,” we used a choice blindness manipulation. In two experiments, participants had to produce a series of arguments in response to reasoning problems, and they were then asked to evaluate other people's arguments about the same problems. Unknown to the participants, in one of the trials, they were presented with their own argument as if it was someone else's. Among those participants who accepted the manipulation and thus thought they were evaluating someone else's argument, more than half (56% and 58%) rejected the arguments that were in fact their own. Moreover, participants were more likely to reject their own arguments for invalid than for valid answers. This demonstrates that people are more critical of other people's arguments than of their own, without being overly critical: They are better able to tell valid from invalid arguments when the arguments are someone else's rather than their own.
Langerhans cell histiocytosis and Erdheim‐Chester disease, both with cutaneous presentations, and papillary thyroid carcinoma all harboring the BRAFV600E mutation
Authors: Johnson William T. , Patel Parth , Hernandez Amanda , Grandinetti Lisa M. , Huen Arthur C. , Marks Stanley , Ho Jonhan , Monaco Sara E. , Jaffe Ronald , Picarsic Jennifer
Published: October 2015

Langerhans cell histocytosis (LCH) and Erdheim‐Chester disease are two rare histiocytic disorders. Their occurrence in the same patient is more infrequent, but has been described. We report a case of a 38‐year‐old woman who presented with a diagnosis of single system cutaneous LCH. Subsequently, she developed multiple papules on her extremities consistent with a non‐LCH xanthogranuloma type lesion. BRAFV600E mutation immunostain, VE1 was positive in the skin lesion, which was confirmed by molecular polymerase chain reaction (PCR) studies, initiating a complete systemic workup for Erdheim‐Chester disease. Systemic involvement was confirmed with bilateral sclerotic bone lesions and retroperitoneal and pelvic fibrosing disease. She was also found to have a BRAFV600E mutation positive papillary thyroid carcinoma. New suspicious cutaneous lesions presenting in patients with a history of LCH need to be biopsied. A BRAFV600E mutation in a non‐LCH histiocytic lesion with a xanthogranuloma phenotype (CD163/CD68/CD14/fascin/Factor 13a) should prompt an Erdheim‐Chester disease workup. This is a unique case of a woman with BRAFV600E mutation positive Erdheim‐Chester disease and cutaneous LCH, while also being, to our knowledge, the first reported case in the English literature of it occurring in a patient with a BRAFV600E mutation positive papillary thyroid carcinoma.
Automated direct immunofluorescence analyses of skin biopsies
Authors: Lemcke Susanne , Sokolowski Siegmar , Rieckhoff Nicole , Buschtez Michael , Kaffka Christian , Winter‐Keil Antje , Schaller Christine , Rottmann Norbert , Sadik Christian D. , Stöcker Winfried , Zillikens Detlef , Schmidt Enno
Published: October 2015

Background

Diagnosis of autoantibody‐ and immune complex‐induced skin diseases is primarily based on direct immunofluorescence (DIF) microscopy. DIF staining is usually performed manually and, therefore, is labor intensive. The quality of immunohistochemical results considerably depends on the experience of the person conducting the tests. The novel EUROTide™ technique in combination with the biochip‐based system EUROPath represents a new technology for automation of DIF staining.

Methods

Frozen sections of previously characterized skin biopsies from bullous pemphigoid and pemphigus vulgaris patients were incubated with fluorescein‐labelled anti‐human IgG and complement C3c following the standard manual procedure and, for comparison, applying EUROTide/EUROPath in an automated version.

Results

Both, the manual and the automated procedure, detected IgG and C3c deposits in all samples. However, DIF stainings performed with EUROTide/EUROPath displayed more intense specific IF signals and distinctly less background staining. The detecting antibody could be used at a ×4 higher dilution.

Conclusion

EUROTide/EUROPath applied in an automated system improves diagnostic accuracy and saves reagents. Larger studies in other routine laboratories may further explore the value of the EUROTide/EUROPath technology and may include comparison with other automated stainers.
Procurement Contracts in the Presence of Endogenous Disruption Risk
Authors: Huang He , Shen Xiaoyu , Xu Hongyan
Published: October 2015

We consider a manufacturer facing an unreliable supplier with high or low type on initial reliability. The private reliability can be enhanced through process improvement initiated by either manufacturer (manufacturer‐initiated improvement, MI) or supplier (supplier‐initiated improvement, SI). We derive optimal procurement contracts for both mechanisms and find that the moral hazard does not necessarily generate more profit for high‐type supplier. Furthermore, information asymmetry causes a greater possibility of not ordering from low type in SI than MI. For low type, when an upward effort distortion appears in both mechanisms, a decreased (increased) unit penalty should be imposed in MI (SI) compared with symmetric information case. Although possibly efficient effort from the supplier could yield greater channel profit in SI, several scenarios violate this expectation. However, the manufacturer's expected profit in MI is no less than that in SI. When MI is extended to MSI where both manufacturer and supplier can exert effort, the expected profits of two parties are equal to those in SI. We further extend SI to SID, where both process improvement and dual‐sourcing are available. The manufacturer considers the trade‐off between the benefit from diversification and the loss from dual information rent to decide to choose SID or MI. By comparing SID with pure dual‐sourcing, we find that supplier's process improvement could either accelerate or retard the exercise of dual‐sourcing.
Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera
Authors: Patel Ryan , Brice Nicola L. , Lewis Richard J. , Dickenson Anthony H.
Published: October 2015

Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin‐2‐induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non‐sentient rats. Subcutaneous injection of 10 nm ciguatoxin‐2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low‐threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6‐({2‐[2‐fluoro‐6‐(trifluoromethyl)phenoxy]‐2‐methylpropyl}carbamoyl)pyridine‐3‐carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co‐injection with the Nav1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold‐evoked neuronal responses were inhibited by antagonists of Nav1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold‐insensitive Nav1.8/TRPA1‐positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin‐induced hypersensitivity.
The effect of ageing on isoniazid pharmacokinetics and hepatotoxicity in Fischer 344 rats
Authors: Mach John , Huizer – Pajkos Aniko , Mitchell Sarah J. , McKenzie Catriona , Phillips Leo , Kane Alice , Jones Brett , de Cabo Rafael , Cogger Victoria , Le Couteur David G. , Hilmer Sarah N.
Published: October 2015

Isoniazid is the first‐line treatment for tuberculosis; however, its use is limited by hepatotoxicity. Age‐related differences in isoniazid pharmacokinetics and hepatotoxicity are uncertain. We aimed to investigate these in young (3 ± 0 months, n = 26) and old (23.0 ± 0.2 months, n = 27) male Fischer 344 rats following a low‐ or high‐dose toxic regimen of isoniazid or vehicle (4 doses/day over 2 days; low: 100, 75, 75, 75 mg/kg; high: 150, 105, 105, 105 mg/kg i.p. every 3 h). Fifteen hours after the last dose, animals were euthanized and sera and livers were prepared for analysis. Isoniazid treatment increased serum hepatotoxicity markers (alanine and aspartate transaminase) in young animals but not in old animals, and only reached significance with the high dose in young animals. Isoniazid treatment caused a trend towards an increase in necrosis in young animals with both doses. In contrast, microvesicular steatosis was increased in old isoniazid‐treated animals, reaching significance only with the low dose (steatosis prevalence in old: vehicle 1/9, isoniazid 4/5; P < 0.05). Among isoniazid‐treated animals, concentrations of toxic intermediates acetylhydrazine and hydrazine were higher in old than young animals (P < 0.05). With both doses, hepatic cytochrome P450 2E1 activity was higher in young animals compared with old (P < 0.05). There were no other age effects seen on any of the other measured enzymes involved in isoniazid metabolism (N‐acetyl transferase, amidase, glutathione‐S‐transferase). These results show age‐related changes in isoniazid pharmacokinetics may contribute towards differential patterns of toxicity and confirm that standard hepatotoxicity markers do not detect isoniazid‐induced microvesicular steatosis.
Genes located in a chromosomal inversion are correlated with territorial song in white‐throated sparrows
Authors: Zinzow‐Kramer W. M. , Horton B. M. , McKee C. D. , Michaud J. M. , Tharp G. K. , Thomas J. W. , Tuttle E. M. , Yi S. , Maney D. L.
Published: October 2015

The genome of the white‐throated sparrow (Zonotrichia albicollis) contains an inversion polymorphism on chromosome 2 that is linked to predictable variation in a suite of phenotypic traits including plumage color, aggression and parental behavior. Differences in gene expression between the two color morphs, which represent the two common inversion genotypes (ZAL2/ZAL2 and ZAL2/ZAL2m), may therefore advance our understanding of the molecular underpinnings of these phenotypes. To identify genes that are differentially expressed between the two morphs and correlated with behavior, we quantified gene expression and terrirorial aggression, including song, in a population of free‐living white‐throated sparrows. We analyzed gene expression in two brain regions, the medial amygdala (MeA) and hypothalamus. Both regions are part of a ‘social behavior network’, which is rich in steroid hormone receptors and previously linked with territorial behavior. Using weighted gene co‐expression network analyses, we identified modules of genes that were correlated with both morph and singing behavior. The majority of these genes were located within the inversion, showing the profound effect of the inversion on the expression of genes captured by the rearrangement. These modules were enriched with genes related to retinoic acid signaling and basic cellular functioning. In the MeA, the most prominent pathways were those related to steroid hormone receptor activity. Within these pathways, the only gene encoding such a receptor was ESR1 (estrogen receptor 1), a gene previously shown to predict song rate in this species. The set of candidate genes we identified may mediate the effects of a chromosomal inversion on territorial behavior.
A glial K+/Cl− cotransporter modifies temperature‐evoked dynamics in Caenorhabditis elegans sensory neurons
Authors: Yoshida A. , Nakano S. , Suzuki T. , Ihara K. , Higashiyama T. , Mori I.
Published: October 2015

K+/Cl− cotransporters (KCCs) are known to be crucial in the control of neuronal electrochemical Cl− gradient. However, the role of these proteins in glial cells remains largely unexplored despite a number of studies showing expression of KCC proteins in glial cells of many species. Here, we show that the Caenorhabditis elegans K+/Cl− cotransporter KCC‐3 is expressed in glial‐like cells and regulates the thermosensory behavior through modifying temperature‐evoked activity of a thermosensory neuron. Mutations in the kcc‐3 gene were isolated from a genetic screen for mutants defective in thermotaxis. KCC‐3 is expressed and functions in the amphid sheath glia that ensheathes the AFD neuron, a major thermosensory neuron known to be required for thermotaxis. A genetic analysis indicated that the regulation of the thermosensory behavior by KCC‐3 is mediated through AFD, and we further show that KCC‐3 in the amphid sheath glia regulates the dynamics of the AFD activity. Our results show a novel mechanism by which the glial KCC‐3 protein non‐cell autonomously modifies the stimulus‐evoked activity of a sensory neuron and highlights the functional importance of glial KCC proteins in modulating the dynamics of a neural circuitry to control an animal behavior.
Enhanced winter soil frost reduces methane emission during the subsequent growing season in a boreal peatland
Authors: Zhao Junbin , Peichl Matthias , Nilsson Mats B.
Published: October 2015

Winter climate change may result in reduced snow cover and could, consequently, alter the soil frost regime and biogeochemical processes underlying the exchange of methane (CH4) in boreal peatlands. In this study, we investigated the short‐term (1–3 years) vs. long‐term (11 years) effects of intensified winter soil frost (induced by experimental snow exclusion) on CH4 exchange during the following growing season in a boreal peatland. In the first 3 years (2004–2006), lower CH4 emissions in the treatment plots relative to the control coincided with delayed soil temperature increase in the treatment plots at the beginning of the growing season (May). After 11 treatment years (in 2014), CH4 emissions were lower in the treatment plots relative to the control over the entire growing season, resulting in a reduction in total growing season CH4 emission by 27%. From May to July 2014, reduced sedge leaf area coincided with lower CH4 emissions in the treatment plots compared to the control. From July to August, lower dissolved organic carbon concentrations in the pore water of the treatment plots explained 72% of the differences in CH4 emission between control and treatment. In addition, greater Sphagnum moss growth in the treatment plots resulted in a larger distance between the moss surface and the water table (i.e., increasing the oxic layer) which may have enhanced the CH4 oxidation potential in the treatment plots relative to the control in 2014. The differences in vegetation might also explain the lower temperature sensitivity of CH4 emission observed in the treatment plots relative to the control. Overall, this study suggests that greater soil frost, associated with future winter climate change, might substantially reduce the growing season CH4 emission in boreal peatlands through altering vegetation dynamics and subsequently causing vegetation‐mediated effects on CH4 exchange.
Response to CO2 enrichment of understory vegetation in the shade of forests
Authors: Kim Dohyoung , Oren Ram , Qian Song S.
Published: October 2015

Responses of forest ecosystems to increased atmospheric CO2 concentration have been studied in few free‐air CO2 enrichment (FACE) experiments during last two decades. Most studies focused principally on the overstory trees with little attention given to understory vegetation. Despite its small contribution to total productivity of an ecosystem, understory vegetation plays an important role in predicting successional dynamics and future plant community composition. Thus, the response of understory vegetation in Pinus taeda plantation at the Duke Forest FACE site after 15–17 years of exposure to elevated CO2, 6–13 of which with nitrogen (N) amendment, was examined. Aboveground biomass and density of the understory decreased across all treatments with increasing overstory leaf area index (LAI). However, the CO2 and N treatments had no effect on aboveground biomass, tree density, community composition, and the fraction of shade‐tolerant species. The increases of overstory LAI (~28%) under elevated CO2 resulted in a reduction of light available to the understory (~18%) sufficient to nullify the expected growth‐enhancing effect of elevated CO2 on understory vegetation.
Field Evaluation of Cocksfoot, Tall Fescue and Phalaris for Dry Marginal Environments of South‐Eastern Australia. 1. Establishment and Herbage Production
Authors: Clark S. G. , Nie Z. N. , Culvenor R. A. , Harris C. A. , Hayes R. C. , Li G. D. , Norton M. R. , Partington D. L.
Published: October 2015

Newly developed candidate cultivars of cocksfoot (Dactylis glomerata L.), phalaris (Phalaris aquatica L.) and tall fescue (Festuca arundinacea Schreb. = syn. L. arundinaceum (Schreb) Darbysh.) were evaluated over four years for persistence and productivity against current commercial cultivars in small plots at five locations selected for lower and less reliable rainfall and difficult soils (low pH and high Al) in south‐eastern Australia known to be marginally too dry for these grass species. The five locations were ‐ representing summer dominant rainfall, Inverell, in northern New South Wales (NSW); ‐ representing uniform rainfall; Trungley Hall, (medium rainfall), and Beckom (lower rainfall) both in southern NSW; and; representing a winter dominant pattern ‐ Eversley, (higher rainfall), and Bealiba, (lower rainfall), in central Victoria. The objective was to determine if the new candidate cultivars were more likely to persist and to be productive than current commercial cultivars. The study showed that most phalaris and cocksfoot treatments were highly productive in high rainfall years at one or both sites in southern NSW. However, all treatments had become much less productive by the end of the experimental period due to plant loss under hot, dry conditions in the final summer. At Bealiba in central Victoria, cocksfoot was the most productive species with several cocksfoot treatments of both subsp. hispanica and subsp. glomerata still present at the final harvest despite a hot and dry final summer‐autumn. Tall fescue was the most productive species in the two higher rainfall environments (Inverell, Eversley) although most treatments of all species performed well at those sites. Continental tall fescues were more productive on average than Mediterranean tall fescues at the strongly acidic Eversley site. As a result of this work, two of the new cocksfoot candidates (Moroccan Fine and AVH48 Selection) and one of the tall fescue candidates (Summer Active 1) have been licensed for commercial development and release.
A review of sugar consumption from nationally representative dietary surveys across the world
Authors: Newens K. J. , Walton J.
Published: October 2015

Background

Government and health organisations worldwide have recently reviewed the evidence on the role of dietary sugars in relation to health outcomes. Hence, it is timely to review current intakes of dietary sugars with respect to this guidance and as a benchmark for future surveillance.

Methods

This review collates data from nationally representative dietary surveys across the world and reports estimates of intakes of total and added sugars, and sucrose in different population subgroups. Total sugars includes all mono‐ and disaccharides; namely, glucose, fructose, lactose, sucrose and maltose. Added and free sugars differ in the quantity of natural sugars included in their definitions. Free sugars include sugars naturally present in honey, syrups, fruit juices and fruit juice concentrates, whereas added sugars typically only refer to those added during processing.

Results

Most countries reported intakes of total sugars, with fewer reporting intakes of added sugars and sucrose. No country reported intakes of free sugars. The available data suggest that total sugars as a percentage of energy were highest in the infant (<4 years), with mean values ranging from 20.0% to 38.4%, and decreased over the lifespan to 13.5–24.6% in adults. Intakes of added sugars were higher in school‐aged children and adolescents (up to 19% of total energy) compared to younger children or adults.

Conclusions

Further research into the dietary patterns contributing to added sugars intake in children and adolescents is warranted. It would also be beneficial to policy guidance if future dietary surveys employed a uniform way of expressing sugars that is feasible to measure and has public health significance.
Dynamical electron diffraction simulation for non‐orthogonal crystal system by a revised real space method
Authors: LV C.L. , LIU Q.B. , CAI C.Y. , HUANG J. , ZHOU G.W. , WANG Y.G.
Published: October 2015

In the transmission electron microscopy, a revised real space (RRS) method has been confirmed to be a more accurate dynamical electron diffraction simulation method for low‐energy electron diffraction than the conventional multislice method (CMS). However, the RRS method can be only used to calculate the dynamical electron diffraction of orthogonal crystal system. In this work, the expression of the RRS method for non‐orthogonal crystal system is derived. By taking Na2Ti3O7 and Si as examples, the correctness of the derived RRS formula for non‐orthogonal crystal system is confirmed by testing the coincidence of numerical results of both sides of Schrödinger equation; moreover, the difference between the RRS method and the CMS for non‐orthogonal crystal system is compared at the accelerating voltage range from 40 to 10 kV. Our results show that the CMS method is almost the same as the RRS method for the accelerating voltage above 40 kV. However, when the accelerating voltage is further lowered to 20 kV or below, the CMS method introduces significant errors, not only for the higher‐order Laue zone diffractions, but also for zero‐order Laue zone. These indicate that the RRS method for non‐orthogonal crystal system is necessary to be used for more accurate dynamical simulation when the accelerating voltage is low. Furthermore, the reason for the increase of differences between those diffraction patterns calculated by the RRS method and the CMS method with the decrease of the accelerating voltage is discussed.
Labor Dystocia: Uses of Related Nomenclature
Authors: Neal Jeremy L. , Ryan Sharon L. , Lowe Nancy K. , Schorn Mavis N. , Buxton Margaret , Holley Sharon L. , Wilson‐Liverman Angela M.
Published: October 2015

Introduction

Labor dystocia (slow or difficult labor or birth) is the most commonly diagnosed aberration of labor and the most frequently documented indication for primary cesarean birth. Yet, dystocia remains a poorly specified diagnostic category, with determinations often varying widely among clinicians. The primary aims of this review are to 1) summarize definitions of active labor and dystocia, as put forth by leading professional obstetric and midwifery organizations in world regions wherein English is the majority language and 2) describe the use of dystocia and related terms in contemporary research studies.

Methods

Major national midwifery and obstetric organizations from qualifying United Nations‐member sovereign nations and international organizations were searched to identify guidelines providing definitions of active labor and dystocia or related terms. Research studies (2000‐2013) were systematically identified via PubMed, MEDLINE, and CINAHL searches to describe the use of dystocia and related terms in contemporary scientific publications.

Results

Only 6 organizational guidelines defined dystocia or related terms. Few research teams (n = 25 publications) defined dystocia‐related terms with nonambiguous clinical parameters that can be applied prospectively. There is heterogeneity in the nomenclature used to describe dystocia, and when a similar term is shared between guidelines or research publications, the underlying definition of that term is sometimes inconsistent between documents.

Discussion

Failure to define dystocia in evidence‐based, well‐described, clinically meaningful terms that are widely acceptable to and reproducible among clinicians and researchers is concerning at both national and global levels. This failure is particularly problematic in light of the major contribution of this diagnosis to primary cesarean birth rates.
In vivo and ex vivo regulation of breast cancer resistant protein (Bcrp) by peroxisome proliferator‐activated receptor alpha (Pparα) at the blood–brain barrier
Authors: Hoque Md. Tozammel , Shah Arpit , More Vijay , Miller David S. , Bendayan Reina
Published: October 2015

Breast cancer resistance protein (Bcrp/Abcg2) localized at the blood–brain barrier (BBB) limits permeability into the brain of many xenobiotics, including pharmacological agents. Peroxisome proliferator‐activated receptor α (Pparα), a ligand‐activated transcription factor, primarily involved in lipid metabolism, has been shown to regulate the functional expression of Bcrp in human cerebral microvascular endothelial cells (hCMEC/D3). The aim of this study was to investigate ex vivo and in vivo, the regulation of Bcrp by Pparα in an intact BBB. Ex vivo quantitative real‐time PCR and immunoblot analyses showed significant up‐regulation of Abcg2/Bcrp mRNA and protein levels in CD‐1 mouse brain capillaries incubated with clofibrate, a Pparα ligand. Fluorescence‐based transport assays in CD‐1 and C57BL/6 brain capillaries showed that exposure to clofibrate significantly increased Bcrp transport activity. This increase was not observed in capillaries isolated from Pparα knockout mice. In vivo, we found: i) significant Bcrp protein up‐regulation in clofibrate‐dosed CD‐1 and C57BL/6 capillary lysates, but no effect in Pparα knockout capillary lysates, and ii) significantly increased Bcrp transport activity in capillaries isolated from clofibrate‐treated mice. These results demonstrate an increase in Bcrp functional expression by Pparα in brain capillaries, and suggest that Pparα is another nuclear receptor that can contribute to the regulation of membrane efflux transporters and drug permeability at the BBB.

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We propose the involvement of the following pathways in clofibrate‐mediated induction of the drug transporter Abcg2/Bcrp mRNA, protein expression and function by the nuclear receptor Pparα, in mouse brain capillary endothelial cells. Upon activation with clofibrate (Pparα, ligand), Pparα complex translocates from the cytoplasm into the nucleus and further recruits coactivators and transcription machinery which induce the transcription of Abcg2 gene and ultimately results in upregulation of Bcrp protein expression and function. These findings have significant implications since Bcrp is known to play an important role at the BBB in preventing the permeability of several xenobiotics and drugs into the brain.
Epothilone D prevents binge methamphetamine‐mediated loss of striatal dopaminergic markers
Authors: Killinger Bryan A , Moszczynska Anna
Published: October 2015

Exposure to binge methamphetamine (METH) can result in a permanent or transient loss of dopaminergic (DAergic) markers such as dopamine (DA), dopamine transporter, and tyrosine hydroxylase (TH) in the striatum. We hypothesized that the METH‐induced loss of striatal DAergic markers was, in part, due to a destabilization of microtubules (MTs) in the nigrostriatal DA pathway that ultimately impedes anterograde axonal transport of these markers. To test this hypothesis, adult male Sprague–Dawley rats were treated with binge METH or saline in the presence or absence of epothilone D (EpoD), a MT‐stabilizing compound, and assessed 3 days after the treatments for the levels of several DAergic markers as well as for the levels of tubulins and their post‐translational modifications (PMTs). Binge METH induced a loss of stable long‐lived MTs within the striatum but not within the substantia nigra pars compacta (SNpc). Treatment with a low dose of EpoD increased the levels of markers of stable MTs and prevented METH‐mediated deficits in several DAergic markers in the striatum. In contrast, administration of a high dose of EpoD appeared to destabilize MTs and potentiated the METH‐induced deficits in several DAergic markers. The low‐dose EpoD also prevented the METH‐induced increase in striatal DA turnover and increased behavioral stereotypy during METH treatment. Together, these results demonstrate that MT dynamics plays a role in the development of METH‐induced losses of several DAergic markers in the striatum and may mediate METH‐induced degeneration of terminals in the nigrostriatal DA pathway. Our study also demonstrates that MT‐stabilizing drugs such as EpoD have a potential to serve as useful therapeutic agents to restore function of DAergic nerve terminals following METH exposure when administered at low doses.

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Administration of binge methamphetamine (METH) negatively impacts neurotransmission in the nigrostriatal dopamine (DA) system. The effects of METH include decreasing the levels of DAergic markers in the striatum. We have determined that high‐dose METH destabilizes microtubules in this pathway, which is manifested by decreased levels of acetylated (Acetyl) and detyrosinated (Detyr) α‐tubulin (I). A microtubule stabilizing agent epothilone D protects striatal microtubules form the METH‐induced loss of DAergic markers (II). These findings provide a new strategy for protection form METH ‐ restoration of proper axonal transport.
Time for Each Other: Work and Family Constraints Among Couples
Authors: Flood Sarah M. , Genadek Katie R.
Published: October 2015

Little is known about couples' shared time and how actual time spent together is associated with well‐being. In this study, the authors investigated how work and family demands are related to couples' shared time (total and exclusive) and individual well‐being (happiness, meaningfulness, and stress) when with one's spouse. They used individual‐level data from the 2003–2010 American Time Use Survey (N = 46,883), including the 2010 Well‐Being Module. The results indicated that individuals in full‐time working dual‐earner couples spend similar amounts of time together as individuals in traditional breadwinner–homemaker arrangements on weekdays after accounting for daily work demands. The findings also show that parents share significantly less total and exclusive spousal time together than nonparents, though there is considerable variation among parents by age of the youngest child. Of significance is that individuals experience greater happiness and meaning and less stress during time spent with a spouse opposed to time spent apart.
Role of toll‐like receptor 4 in melatonin‐induced cardioprotection
Authors: Nduhirabandi Frederic , Lamont Kim , Albertyn Zulfah , Opie Lionel H. , Lecour Sandrine
Published: October 2015

Melatonin protects the heart against myocardial ischemia/reperfusion injury via the activation of the survivor activating factor enhancement (SAFE) pathway which involves tumor necrosis factor alpha (TNFα) and the signal transducer and activator of transcription 3 (STAT3). Toll‐like receptor 4 (TLR4) plays a crucial role in myocardial ischemia/reperfusion injury and activates TNFα. In this study, we investigated whether melatonin may target TLR4 to activate the SAFE pathway. Isolated hearts from rats or mice were subjected to ischemia/reperfusion injury. Melatonin (75 ng/L) and/or TAK242 (a specific inhibitor of TLR4 signaling, 500 nm) were administered to the rat hearts before the induction of ischemia. Pre‐ischemic myocardial STAT3 was evaluated by Western blotting. Lipopolysaccharide (LPS, a stimulator of TLR4) was administered to wild type, TNFα receptor 2 knockout or cardiomyocyte‐specific STAT3‐deficient mice (2.8 mg/kg, i.p) 45 min before the heart isolation. Myocardial infarct size was measured as an endpoint. Compared to the control, administration of melatonin reduced myocardial infarct size (34.7 ± 2.8% versus 62.6 ± 2.7%, P < 0.01). This protective effect was abolished in the presence of TAK242 (49.2 ± 6.5%). Melatonin administered alone increased the pre‐ischemic activation of mitochondrial STAT3, and this effect was attenuated with TAK242. Furthermore, stimulation of TLR4 with LPS pretreatment to mice reduced myocardial infarct size of the hearts isolated from wild‐type animals but failed to protect the hearts isolated from TNFα receptor 2‐knockout mice or cardiomyocyte‐specific STAT3‐deficient mice (P < 0.001). Taken together, these data suggest that cardioprotection induced by melatonin is mediated by TLR4 to activate the SAFE pathway.
Characterization of key genes of the renin–angiotensin system in mature feline adipocytes and during in vitro adipogenesis
Authors: Riedel J. , Badewien‐Rentzsch B. , Kohn B. , Hoeke L. , Einspanier R.
Published: October 2015

Obesity is a growing health problem in humans as well as companion animals. In the development and progression of obesity‐associated diseases, the members of the renin–angiotensin system (RAS) are proposed to be involved. Particularly, the prevalence of type 2 diabetes mellitus in cats has increased enormously which is often been linked to obesity as well as to RAS. So far, reports about the expression of a local RAS in cat adipocytes are missing. Therefore, we investigated the mRNA expression of various RAS genes as well as the adipocyte marker genes adiponectin, leptin and PPAR‐γ in feline adipocytes using quantitative PCR. To characterize the gene expression during adipogenesis, feline pre‐adipocytes were differentiated into adipocytes in a primary cell culture and the expression of RAS key genes measured. All major RAS components were expressed in feline cells, but obvious differences in the expression between pre‐adipocytes and the various differentiation stages were found. Interestingly, the two enzymes ACE and ACE2 showed an opposite expression course. In addition to the in vitro experiments, mature adipocytes were isolated from subcutaneous and visceral adipose tissue. Significant differences between both fat depots were found for ACE as well as AT1 receptor with greater expression in subcutaneous than in visceral adipocytes. Visceral adipocytes had significantly higher adiponectin and PPAR‐γ mRNA level compared to the subcutaneous fat cells. Concerning the nutritional status, a significant lower expression of ACE2 was measured in subcutaneous adipocytes of overweight cats. In summary, the results show the existence of a potentially functional local RAS in feline adipose tissue which is differentially regulated during adipogenesis and dependent on the fat tissue depot and nutritional status. These findings are relevant for understanding the development of obesity‐associated diseases in cats such as diabetes mellitus.
Effect of raw soya bean particle size on productive performance and digestion of dairy cows
Authors: Naves A. B. , Freitas Júnior J. E. , Barletta R. V. , Gandra J. R. , Calomeni G. D. , Gardinal R. , Takiya C. S. , Vendramini T. H. A. , Mingoti R. D. , Rennó F. P.
Published: October 2015

Differing soya bean particle sizes may affect productive performance and ruminal fermentation due to the level of fatty acid (FA) exposure of the cotyledon in soya bean grain and because the protein in small particles is more rapidly degraded than the protein in large particles, which influence ruminal fibre digestion and the amounts of ruminally undegradable nutrients. The objective of this experiment was to investigate the effects of raw soya bean particle size on productive performance, digestion and milk FA profile of dairy cows. Twelve Holstein cows were assigned to three 4 × 4 Latin squares with 21‐day periods. At the start of the experiment, cows were 121 days in milk (DIM) and yielded 30.2 kg/day of milk. Cows were fed 4 diets: (i) control diet (CO), without raw soya bean; (ii) whole raw soya bean (WRS); (iii) cracked raw soya bean in Wiley mill 4‐mm screen (CS4); and (iv) cracked raw soya bean in Wiley mill 2‐mm screen (CS2). The inclusion of soya beans (whole or cracked) was 200 g/kg on dry matter (DM) basis and partially replaced ground corn and soya bean meal. Uncorrected milk yield and composition were not influenced by experimental diets; however, fat‐corrected milk (FCM) decreased when cows were fed soya bean treatments. Soya bean diets increased the intake of ether extract (EE) and net energy of lactation (NEL), and decreased the intake of DM and non‐fibre carbohydrate (NFC). Ruminal propionate concentration was lower in cows fed WRS than cows fed CS2 or CS4. Cows fed cracked raw soya bean presented lower nitrogen in faeces than cows fed WRS. The milk of cows fed WRS, CS2 and CS4 presented higher unsaturated FA than cows fed CO. The addition of raw soya bean in cow diets, regardless of the particle size, did not impair uncorrected milk yield and nutrient digestion, and increased the concentration of unsaturated FA in milk. Cows fed cracked raw soya bean presented similar productive performance to cows fed whole raw soya bean.