bluuebunny/crossref_metadata_2025 huggingface dataset:
How often do Protein Genes Navigate Valleys of Low Fitness?
Authors: Nelson Erik D. , Grishin Nick V.
Published: March 2019

In order escape from local fitness peaks, a population must navigate across valleys of low fitness. How these transitions occur, and what role they play in adaptation, have been subjects of active interest in evolutionary genetics for almost a century. However, to our knowledge, this problem has never been addressed directly, by considering the evolution of a gene, or group of genes, as a whole, including the complex effects of fitness interactions among multiple loci. Here, we use a precise model of protein fitness to compute the probabilityP(s, Δt) that an allele, randomly sampled from a population at timet, has crossed a fitness valley of depthsduring an interval [t− Δt, t] in the immediate past. We study populations of model genes evolving under equilibrium conditions consistent with those in mammalian mitochondria. From this data, we estimate that genes encoding small protein motifs navigate fitness valleys of depth 2Ns≳ 30 with probabilityP≳ 0.1 on a time scale of human evolution, whereNis the (mitochondrial) effective population size. The results are consistent with recent findings for Watson–Crick switching in mammalian mitochondrial tRNA molecules.
EPS8 facilitates uncoating of influenza A virus
Authors: Larson Gloria P. , Tran Vy , Yú Shuǐqìng , Caì Yíngyún , Higgins Christina A. , Smith Danielle M. , Baker Steven F. , Radoshitzky Sheli R. , Kuhn Jens H. , Mehle Andrew
Published: March 2019

All viruses balance interactions between cellular machinery co-opted to support replication and host factors deployed to halt the infection. We used gene correlation analysis to perform an unbiased screen for host factors involved in influenza A virus (FLUAV) infection. Our screen identified the cellular factor epidermal growth factor receptor pathway substrate 8 (EPS8) as the highest confidence pro-viral candidate. Knockout and overexpression of EPS8 confirmed its importance in enhancing FLUAV infection and titers. Loss of EPS8 did not affect virion attachment, uptake, or fusion. Rather, our data show that EPS8 specifically functions during virion uncoating. EPS8 physically associated with incoming virion components, and subsequent nuclear import of released ribonucleoprotein complexes was significantly delayed in the absence of EPS8. Our study identified EPS8 as a host factor important for uncoating, a crucial step of FLUAV infection during which the interface between the virus and host is still being discovered.
Proteomic characterization of theMycobacterium marinum-containing vacuole inDictyostelium discoideum
Authors: Guého Aurélie , Bosmani Cristina , Nitschke Jahn , Soldati Thierry
Published: March 2019

Mycobacterium tuberculosis, the causative agent of tuberculosis, is able to manipulate the phagosome compartment in which it resides in order to establish a permissive replicative compartment called theMycobacterium-containing vacuole (MCV).Mycobacterium marinum, a fish pathogen and a close relative of the tuberculosis group, is able to infect the free-living amoeba and professional phagocyteDictyostelium discoideumand to manipulate its phagosome maturation. By using this host-pathogen model system, we have established an innovative process to isolate MCVs. This procedure allowed us to isolate theM. marinum-MCV at 1, 3 and 6 hours post infection to study the earlyM. marinum-MCV proteome. By using isobaric labelling and mass spectrometry, we quantitatively compared the proteomic composition of those MCVs isolated at different stages of the early infection phase to understand howM. marinumimpacts on this compartment to divert it from the normal phagosomal pathway. Furthermore, we also compared the manipulated compartmentM. marinum-MCV to non- or less manipulated compartments containing different mycobacteria strains: the non-pathogenicM. smegmatis, the avirulentM. marinum-L1D or the attenuatedM. marinum-RD1.
Regulation of cAMP accumulation and activity by distinct phosphodiesterase subtypes in INS-1 cells and human pancreatic β-cells
Authors: Pratt Evan P.S. , Harvey Kyle E. , Salyer Amy E. , Tang Shiqi , Hockerman Gregory H.
Published: March 2019

Pancreatic β-cells express multiple phosphodiesterase (PDE) subtypes, but the specific roles for each in β-cell function, particularly in humans, is not clear. We evaluated the cellular role of PDE1, PDE3, and PDE4 activity in the rat insulinoma cell line INS-1 and in primary human β-cells using subtype-selective PDE inhibitors. Using a genetically encoded, FRET-based cAMP sensor, we found that the PDE1 inhibitor 8MM-IBMX and the PDE4 inhibitor rolipram elevated cAMP levels above baseline in the absence and presence of 18 mM glucose in INS-1 cells. Inhibition of PDE1 or PDE4 potentiated glucose-stimulated insulin secretion in INS-1 cells. In contrast, the inhibition of PDE3 with cilostamide had little effect on cAMP levels or glucose-stimulated insulin secretion. PDE1 inhibition, but not PDE3 of PDE4 inhibition, reduced palmitate-induced caspase-3/7 activation, and enhanced CREB phosphorylation in INS-1 cells. In human β-cells, only PDE3 or PDE4 inhibition increased cAMP levels in 1.7 mM glucose, but PDE1, PDE3, or PDE4 inhibition potentiated cAMP levels in 16.7 mM glucose. Inhibition of PDE1 or PDE4 increased cAMP levels to a greater extent in 16.7 mM glucose than in 1.7 mM glucose in human β-cells. In contrast, elevation of cAMP levels by PDE3 inhibition was not different at these glucose concentrations. PDE1 inhibition also potentiated insulin secretion from human islets, suggesting that the role of PDE1 may be conserved between INS-1 cells and human pancreatic β-cells. Our results suggest that inhibition of PDE1 may be a useful strategy to potentiate glucose-stimulated insulin secretion, and to protect β-cells from the toxic effects of excess fatty acids.
An analysis of academic librarians competencies and skills for implementation of Big Data analytics in libraries
Authors: Ahmad Khurshid , JianMing Zheng , Rafi Muhammad
Published: March 2019

Purpose

The purpose of this paper is to analyze the views and capabilities of librarians for the implementation of Big Data analytics in academic libraries of Pakistan. The study also sets out to check the relationship between the required skills of librarians and the application of Big Data analytics.

Design/methodology/approach

A survey was conducted to gather the required data from the targeted audience. The targeted population of the study was Head/In charge library managers of Pakistani university libraries, which were 173 in total. All the respondents (academic librarians) were invited through an e-mail to respond to the survey voluntarily. Out of 173 respondents from higher education commission of Pakistan chartered university libraries, 118 librarians (68.2 percent) completed the survey that was finally considered, and after checking data, recommendation for analysis was made. To analyze the collected data, statistical technique Pearson correlation was applied using statistical package for social science version 25 to know the strength of the mutual correlation of variables.

Findings

The findings of the study show a strong correlation between the required competencies and skills of librarians for the implementation of Big Data analytics in academic libraries. In all variables of the study, the correlation was highly significant, except two of the variables, including “concept of Big Data” and “different forms of data.” The study also reveals that most of the respondents were well aware of the concept of Big Data analytics. Moreover, they were using a large amount of data to carry out various library operations, including the acquisition, preservation, curation and analysis of data.

Originality/value

This study is significant in the sense that it fills a substantial gap in the literature regarding the perspective of librarians on Big Data analytics.
Vulnerability analysis of building structures to floods
Authors: Kikwasi Geraldine , Mbuya Elinorata
Published: March 2019

Purpose

There is evidence of increasing urban floods being aftermath of climate change. The purpose of this paper is to present findings-related analysis of vulnerability of building structures in informal settlements to floods and associated coping strategies.

Design/methodology/approach

The study adopted a case study strategy, supported by field surveys and laboratory experiments. The informal settlement taken as case study is Sunna sub-ward. Field surveys involved interviews, questionnaires and observations and tests were conducted to determine the strength of walls, blocks and mortar.

Findings

The findings reveal that vulnerability of building structures to floods are due to poor quality of materials used in construction of houses which are influenced by income levels, location (lower areas of Sunna sub-ward) and inadequate storm water drainage system. Moreover, socio-economic vulnerabilities do exist in the settlements and are related to lack of peace of mind, outbreak of disease and expenses related to repairing of flood affected houses. Coping strategies used in the sub-ward for built structures are building barrier walls at the front door of the house and use multiple strategies which are supported by reactive and recovery strategies.

Research limitations/implications

The findings of this study were mostly affected by limited knowledge of respondents on construction materials and processes.

Practical implications

Findings of the paper provide an insight on the effects of climate change on building structures in informal settlements and coping strategies in place to protect buildings. The outputs can be used for any other informal settlement in Dar es Salaam the only limitation is the terrain.

Originality/value

The paper recommends use of quality building materials and technicians/artisans, improvement of surface water drainage and training of residents on the effects of climate change and variability. In addition, promising coping strategies should be adopted while those under-performing should be discouraged as they increase the cost burden among the urban poor.
Infrastructure and economic development in developing economies
Authors: Luu Hiep Ngoc , Nguyen Ngoc Minh , Ho Hai Hong , Tien Dao Ngoc
Published: March 2019

Purpose

The purpose of this paper is to empirically investigate the impact of infrastructure on economic development in developing economies.

Design/methodology/approach

A panel data analysis approach is utilised to evaluate the influence of various types of infrastructure on economic development in Vietnam over the period 2003–2013. Specifically, this study uses spatial night-light data taken from NASA’s satellite as an alternative proxy for economic development.

Findings

The analyses indicate that infrastructure enhancement consistently exerts a positive effect on the economy. Upon further investigations of the channels through which infrastructure could affect economic development, the empirical results reveal, in addition, that the developmental impact of infrastructure tends to be stronger if more rigorous government supervision and oversight of the construction and delivery of infrastructure projects are in place to ensure the efficiency and effectiveness of the private sector’s investment in infrastructure facilities. Finally, the interaction of infrastructure with human capital appears to exert an especially important influence upon economic development.

Originality/value

This study contributes to the debate over whether infrastructure has a real developmental effect in developing countries. Some important policy implications are then drawn from the empirical analysis. As a result, this paper will be of value to other researchers, economists, business leaders and policy-makers attempting to understand the economic benefit of infrastructure development.
Experimental investigation of tribological effect on vegetable oil with CuO nanoparticles and ZDDP additives
Authors: Kumar Gitesh , Garg Hem Chander , Gijawara Ajay
Published: March 2019

Purpose

This paper aims to report the friction and wear characteristics of refined soybean oil (RSBO) blended with copper oxide (CuO) nanoparticles and zinc dialkyldithiophosphate (ZDDP) as additives.

Design/methodology/approach

Four different concentrations 0.04, 0.05, 0.1 and 0.2 Wt.% of CuO nanoparticles were added with ZDDP in RSBO. The friction and wear characteristics of lubricants have been investigated on a pin-on-disc tribotester under loads of 120 and 180 N, with rotating speeds of 1,200 and 1,500 rpm in half hour of operating time. The dispersion stability of CuO nanoparticles has been analyzed using ultraviolet visible (UV-Vis) spectroscopy. The wearout surface of pins has been examined by using a scanning electron microscope.

Findings

The results revealed that there is a reduction in the friction and wear by the addition of CuO nanoparticles and ZDDP in RSBO. Coefficient of friction increases at a high sliding speed for RSBO with ZDDP. From UV-Vis spectroscopy, it is observed that 100 ml of oleic acid surfactant per gram of CuO nanoparticles has stable dispersion in RSBO.

Originality/value

The addition of ZDDP and CuO nanoparticles in RSBO is more efficient to reduce the friction and wear in comparison to base oil. The optimum concentration of CuO nanoparticles in RSBO is 0.05 Wt.%.
Biodegradation behavior and tribological properties of ultrahigh molecular weight polyethylene stabilized with α-tocopherol
Authors: Kang Xueqin , Yao Chi , Ge Shirong
Published: March 2019

Purpose

This paper aims to investigate the effect of simulated body fluid (SBF) on biodegradation and tribological properties of ultrahigh molecular weight polyethylene (UHMWPE) and UHMWPE stabilized with α-tocopherol.

Design/methodology/approach

The samples of UHMWPE and UHMWPE stabilized with α-tocopherol were prepared by a hot-pressing method, and then immersed in SBF for one year. Tribological test was performed on a UMT-2 tribometer.

Findings

The crystallinity and tribological properties increased slightly after UHMWPE stabilized with α-tocopherol, whereas the O/C ration decreased slightly. The crystallinity and O/C ratio increased after all samples immersed in SBF for one year. This resulted in the deterioration of tribological properties and the wear mechanism change. The tribological properties change was smaller in UHMWPE stabilized with α-tocopherol than that in UHMWPE, because the oxidation resistance of UHMWPE was increased by α-tocopherol.

Originality/value

The results of the experimental studies demonstrated and compared the biodegradation behavior and tribological properties of UHMWPE, UHMWPE stabilized with α-tocopherol, and after they immersed in SBF for one year.
The transactional asset pricing approach
Authors: Michaletz Vladimir , Artemenkov Andrey I.
Published: March 2019

Purpose

The purpose of this paper is to present a methodology based on the transactional asset pricing approach (TAPA) and to illustrate the application of TAPA within the context of professional property valuation.

Design/methodology/approach

The TAPA is a novel analytical valuation methodology recasting the traditional derivations of the income approach techniques, including DCF, from a transactional perspective based on the principle of inter-temporal transactional equity, instead of the conventional investor-specific view originating from I. Fisher (1907, 1930).

Findings

The authors present DCF analysis as a specific case of a more general TAPA approach to valuation under the income method. This also leads to novel analytical derivations of the Direct income capitalization, Gordon, Inwood, Hoskold and Ring models. Based on the TAPA framework, the authors also research the value-enhancing effects of benchmark market volatility on the subject property value and conclude that such effects can be statistically significant depending on the DCF analysis period.

Research limitations/implications

The research has a direct bearing on time-variable discount rate forecasting capabilities, as it uses a time-variant structure for the discount rates.

Practical implications

Using the US Case-Shiller and BLS rental indices as a valuation benchmark, the paper contains an example of applying the general TAPA framework to value a notional property under a TAPA’s DCF version. Such property valuations can be easily replicated in practice – especially in the context of equitable/fair value determination under the International Valuation Standards Council valuation standards.

Social implications

TAPA is a deductive principles-based theory of asset valuation especially fit for the transactional and illiquid asset valuation contexts – thus enabling a more efficient pricing for such assets in a sense of reflecting the transactional interests of the parties more closely than achievable under the conventional valuation methods.

Originality/value

TAPA is an original filiation of research with roots going as far back as Aristotelian Catallactics. It contains analytical formalizations of certain transactional equity principles.
Nostalgic advertising: managing ambivalence to make it work
Authors: Srivastava Ekta , Maheswarappa Satish S. , Sivakumaran Bharadhwaj
Published: March 2019

Purpose

The purpose of this paper is to study the affective outcome of ambivalent nostalgia through use of executional variables, develop a framework linking nostalgia (through affect) and consumers’ cognitive processing, and explain the relationship of nostalgia with self-brand connection (SBC) and willingness to pay a premium (WTPP) through a mediator, cognitive processing.

Design/methodology/approach

This research is based on two experiments. In study 1, students were shown a nostalgic ad paired with a vignette to manipulate “past–present contrast.” In study 2, positive and negative moods were induced and an informative nostalgic ad was shown to measure processing styles and SBC and WTPP; this was followed by mediation analysis.

Findings

The findings are as follows: first, “Past–present contrast” can reduce the negative affect in nostalgia, making it less ambivalent; second, positive (negative) affect leads to top-down (bottom-up) processing; third, SBC and WTPP are higher when top-down processing is used; and, fourth, processing style is a mediator between affect and SBC/WTPP.

Practical implications

Managers may use the “good past, good present” scenario to mitigate negative affect in nostalgia. Nostalgic ads may be used by brands that want consumers to pay a price premium, have a strong SBC and when they want consumers to use top-down processing.

Originality/value

This paper demonstrates how to reduce ambivalence and associate brands with positive affect in nostalgia, and gain SBC and WTPP; the mediating role of cognitive processing in the relationship of nostalgia with SBC and WTPP is delineated.
Racial hair: the persistence and resistance of a category
Authors: Tarlo Emma
Published: March 2019

This article analyses how hair and race are entangled both within anthropology and in the commercial world of the billion‐dollar global market for human hair. Focusing in particular on detached hair, it explores the recurring dynamic through which hair is racialized, on the one hand, and resists racialization, on the other. This process is traced in three interrelated contexts, the roots of which are embedded in historical conditions of domination and oppression. The first is that of nineteenth‐ and early twentieth‐century physical anthropology, when hair was thought to provide a key to racial distinctions. The second refers to contemporary black hair cultures in which hair is racialized both in the marketplace, where it is advertised through ethnic signifiers, and in the natural hair movement, which relies on ideas of authenticity based on biological differences. The third context is that of factories in China, where items such as ‘Brazilian’ hair extensions and ‘Afro’ wigs are physically manufactured through combinations of hair and labour that confound ethnic, racial, and national boundaries. By shifting attention to the materiality of hair, the article highlights the enduring materiality of race, exposing its shape‐shifting qualities and persistent ideologies and providing a unique angle onto the dynamics of nature‐culture articulations.
The association between alcohol access and alcohol‐attributable emergency department visits in Ontario, Canada
Authors: Myran Daniel T. , Chen Jarvis T. , Giesbrecht Norman , Rees Vaughan W.
Published: March 2019

Background and aims

The availability of alcohol through retail outlets is associated with alcohol‐related harms, but few studies have demonstrated a causal relationship. We investigated the association between alcohol availability and alcohol‐attributable emergency department (ED) visits in the province of Ontario during a period of deregulation of controls on the number of alcohol outlets.

Design

Cross‐sectional and pre–post design

Setting and participants

The study used data from two time‐periods: pre‐deregulation (2013–14) and post‐deregulation (2016–17), to compare rates of ED visits for 513 defined geographic regions in Ontario Canada, called Forward Sortation Areas (FSAs).

Measurements

The primary outcome was the age‐standardized rates of alcohol‐attributable ED visits. We compiled a list of all alcohol retail outlets in Ontario during 2014 and 2017 and matched them to their corresponding FSA. We fitted mixed‐effects Poisson regression models to assess: (a) the cross‐sectional association between number of outlets and hours of operation and ED visits; and (b) the impact of deregulation on ED visits using a difference‐in‐difference approach.

Findings

Alcohol‐attributed ED visits increased 17.8% over the study period: more than twice the rate of increase for all ED visits. Increased hours of operation and numbers of alcohol outlets within an FSA were positively associated with higher rates of alcohol‐attributable ED visits. The increase in ED visits attributable to alcohol was 6% (incident rate ratio = 1.06; 95% confidence interval = 1.04–1.08) greater in FSAs that introduced alcohol sales in grocery stores following deregulation compared with FSAs that did not.

Conclusions

Deregulation of alcohol sales in Ontario, Canada in 2015 was associated with increased emergency department visits attributable to alcohol.
“Human Nature” and the Biology of Everyday Life
Authors: Wolf‐Meyer Matthew
Published: March 2019

Anthropologists are well poised to contribute to an immanent theory of human physiological experiences that accounts for the broad social and environmental influences that shape individual and community experiences of health and disease. This article forwards a theory of “the biology of everyday life” as a means to conceptualize the interactions between institutional expectations of behavior, cultural norms, and biological plasticity. Drawing on a wide variety of research on human sleep, this article shows how the expression of sleep needs vary within and between societies and are shaped primarily not by innate biological drives but cultural norms embedded in the institutions that comprise the infrastructure of everyday life. Embracing perspectives from laboratory scientists, social theorists, and ethnographers, the biology of everyday life offers a way to conceptualize human nature not as a set of drives but a supple interaction of physiological plasticity, cultural expectations, and social organization. [plasticity, social determinants of disease, epigenetics, sleep]
Toll‐like receptor 1 and 10 variations increase asthma risk and review highlights further research directions
Authors: Korppi Matti , Törmänen Sari
Published: March 2019

Aim

This paper summarises variations in the genes encoding toll‐like receptors (TLRs) in relation to the aetiology and outcome of infant bronchiolitis. It compares the literature with research carried out by our group.

Methods

A mini review was conducted to provide context for a study carried out at the Department of Paediatrics, Tampere University Hospital, Finland. In 2000‐2004, 187 infants were hospitalised for bronchiolitis and then followed up: 129 at 1.5 years of age, 166 at 5–7 years of age and 138 at 11–13 years of age.

Results

The review showed that the Finnish bronchiolitis study was the only prospective study on the association between TLRs and the emergence of childhood asthma or lung function reduction after bronchiolitis in infancy. It found that TLR1 and TLR10 variant genotypes were associated with more asthma at 5–7 and 11–13 years, with inconsistent results for the other eight TLR genes. Large population‐based studies were also identified that stressed the importance of the TLR2 subfamily members in childhood asthma.

Conclusion

Our study found that variations in the TLR1 and TLR10 genes increased the asthma risk after bronchiolitis. The mini review calls for further research on the TLR2 subfamily in bronchiolitis and childhood asthma.
Pharmacokinetics, safety and tolerability of the novel β‐hCG derived immunomodulatory compound, EA‐230
Authors: van Groenendael Roger , Aarnoutse Rob , Kox Matthijs , van Eijk Lucas , Pickkers Peter
Published: March 2019

Aims

EA‐230 is a newly developed synthetic linear tetrapeptide (AQGV) derived from the chorionic gonadotropin hormone (β‐hCG). We investigated the pharmacokinetics, safety and tolerability of EA‐230 in healthy subjects using different administration strategies.

Methods

Double‐blind, randomized, placebo‐controlled, dose‐escalating phase I studies in healthy subjects using intravenous administration were conducted. In the single dosage study, 32 subjects were assigned to four single dosage groups (1, 3, 10 or 30 mg/kg). In the multiple dosage study, 24 subjects were assigned to three dosage groups (10, 20 or 30 mg/kg, thrice daily for 3 days). In the continuous dosage study, 24 subjects were assigned to three dosage groups (15, 30, or 90 mg/kg/hour for 2 hours). Pharmacokinetics, safety and tolerability assessments were performed up to 14 days.

Results

The highest dosage of EA‐230 (continuous infusion of 90 mg/kg/hour for 2 hours) showed more than proportional increases in exposure (Cmax136%; AUC0‐last137%), a large volume of distribution (geometric mean and 95% CI: 13 [3–58] L/kg), a high clearance rate (26 [15–43] L/h/kg), and a short half‐life (0.35 [0.13–1.0] minutes). EA‐230 was well tolerated and no safety concerns were observed.

Conclusion

These dose‐escalating phase I studies with different administration strategies reveal a pharmacokinetic profile of EA‐230 with a large volume of distribution and a short half‐life. Furthermore, EA‐230 was well tolerated and no safety issues emerged. These results have enabled further clinical development in a phase IIa trial assessing the pharmacodynamics of this compound during systemic inflammation described elsewhere in this issue.
Changing from the inside out? Examining relationships between overweight identification, dieting behaviours, and body measurements over time
Authors: Jones Janelle M. , Schönherr Deva M. , Zaitsoff Shannon , Pullmer Rachelle
Published: March 2019

Objective

To investigate whether changes in overweight identification were associated with dieting behaviours and body measurements over time.

Design

Longitudinal study with assessments at three time points: before and twice during (i.e., baseline, 6 months, 12 months) a 1‐year self‐directed weight loss attempt.

Method

Eighty individuals with overweight or obesity (classified by BMI ≥ 25) reported their personal (i.e., I see myself as overweight), social (i.e., I identify/feel strong ties with other overweight people), and affective (i.e., I am pleased to be overweight) overweight identification; dieting behaviours (e.g., eat less, exercise, eat more fruit and vegetables); and had their body measurements taken (i.e., weight, height, body fat, waist circumference).

Results

Linear mixed modelling was used to examine between‐person differences and within‐person changes in overweight identification on dieting behaviours and body measurements over time. Between‐person differences mattered for measurements: Higher personal overweight identification was associated with higher BMI, body fat, and waist circumference over time. Higher social overweight identification was associated with higher BMI over time. Within‐person changes mattered for behaviours over time: At 12 months, decreases in social overweight identification were associated with increases in a subset of ‘Eat Less, Move More’ dieting behaviours, but not a subset of ‘Healthy’ dieting behaviours. At 12 months, decreases in affective overweight identification were also associated with increases in ‘Eat Less, Move More’ dieting behaviours.

Conclusion

Addressing different aspects of overweight identification and how they change over time, may harness an important psychological pathway to support behavioural change and health irrespective of weight loss.

Statement of contribution

What is already known on this subject?

Psychological factors, such as self‐concept clarity and weight stigma, are associated with dieting behaviours and body measurements.

Qualitative data suggest that identity change may be tied to dieting behaviours and weight loss.

What does this study add?

New insights into the nature of another psychological factor, overweight identification, among individuals with overweight and obesity attempting to lose weight.

The first quantitative evidence that different aspects of overweight identification, and changes in these aspects of overweight identification over time, influence body measurements and dieting behaviours.
Influence of sildenafil on the purinergic components of nerve‐mediated and urothelial ATP release from the bladder of normal and spinal cord injured mice
Authors: Chakrabarty Basu , Ito Hiroki , Ximenes Manuela , Nishikawa Nobuyuki , Vahabi Bahareh , Kanai Anthony J. , Pickering Anthony E. , Drake Marcus J. , Fry Christopher H.
Published: March 2019

Background and purpose

PDE inhibitors such as sildenafil alleviate lower urinary tract symptoms; however, a complete understanding of their action on the bladder remains unclear. We are investigating the effects of sildenafil, on post and preganglionic nerve‐mediated contractions of the mouse bladder, and neuronal and urothelial ATP release.

Experimental approach

Bladders were used from young (12 weeks), aged (24 months), and spinal cord transected (SCT), mice, for in vitro contractility experiments. An arterially perfused in situ whole mouse model was used to record bladder pressure. Nerve‐mediated contractions were generated by electrical field stimulation (EFS) of postganglionic nerve terminals or the pelvic nerve. ATP release during EFS in intact detrusor strips, and during stretch of isolated mucosa strips, was measured using a luciferin‐luciferase assay.

Key results

Sildenafil (20 μM) inhibited nerve‐mediated contractions in young mice, with an increase in f1/2 values in force–frequency relationships, demonstrating a greater effect at low frequencies. Sildenafil reduced the atropine‐resistant, purinergic component of nerve‐mediated contractions, and suppressed neuronal ATP release upon EFS in vitro. Sildenafil reduced the preganglionic pelvic nerve stimulated bladder pressure recordings in situ; comparable to in vitro experiments. Sildenafil reduced stretch‐induced urothelial ATP release. Sildenafil also relaxed nerve‐mediated contractions in aged and SCT mice.

Conclusion and implications

Sildenafil has a greater effect on the low‐frequency, purinergic‐mediated contractions and suppresses neuronal ATP release. In addition, sildenafil reduces stretch‐induced urothelial ATP release. These results demonstrate a novel action of sildenafil to selectively inhibit ATP release from nerve terminals innervating detrusor smooth muscle and the urothelium.
The potential of memory enhancement through modulation of perineuronal nets
Authors: Duncan James A. , Foster Richard , Kwok Jessica C.F.
Published: March 2019

With an increasingly aging global population, the incidence of neurological diseases such as dementia is set to increase to unmanageable levels, yet there are currently only symptomatic therapies available for treatment. The mechanisms underlying the development of some forms of dementia, such as Alzheimer's disease (AD), are not yet completely elucidated with several competing hypotheses existing. During the closure of the critical period in the brain, significant compositional changes occur to the neural extracellular matrix (ECM). Specifically, condensed mesh‐like structures called perineuronal nets (PNNs) form around subsets of neurons and have a profound effect on axonal growth and limit neuronal plasticity. These PNNs act as a morphological checkpoint and can influence memory and cognition. Manipulating these important ECM structures may provide the key to reactivating plasticity and restoring memory, both of which are severely impaired in AD and other associated neurological diseases. This review explores the current understanding of how PNNs are manipulated and examines potential new methods for PNN modulation.

Linked Articles

This article is part of a themed section on Therapeutics for Dementia and Alzheimer's Disease: New Directions for Precision Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.18/issuetoc
Effect of combined goniotomy and phacoemulsification on intraocular pressure in open‐angle glaucoma patients
Authors: Kim Woo‐Jin , Kim Ju‐Mi , Lee Woo‐Hyuk , Kim Kyoung Nam , Kim Chang‐sik
Published: March 2019

Importance

Although goniotomy is known to be successful in treating congenital glaucoma, its effect in adult glaucoma patients remains unclear.

Background

To evaluate the efficacy and safety of goniotomy performed simultaneously with cataract surgery in treatment of open‐angle glaucoma (OAG).

Design

Retrospective comparative study.

Participants

A total of 76 patients with moderately controlled OAG (intraocular pressure [IOP] ≤ 21 mmHg using medications) undergoing cataract surgery.

Methods

Comparison of patients who underwent the conventional goniotomy during cataract surgery (combined goniotomy group) with those who underwent cataract surgery alone (phaco group).

Main Outcome Measures

Changes in IOP and medications, and complications through 12 months.

Results

Baseline IOP was 18.2 ± 2.4 mmHg in the combined goniotomy group and 17.4 ± 1.9 mmHg in the phaco group; number of medications was 2.6 ± 1.1 and 2.4 ± 0.9, respectively (P > 0.05). The reduction in IOP and medication use from baseline in the combined goniotomy group was significantly greater at 12 months compared to the phaco group (−3.1 ± 2.9 mmHg vs −1.3 ± 2.4 mmHg and −1.2 ± 0.9 vs −0.7 ± 0.9, respectively, both P < 0.05). The success rate was 76.7% in the combined goniotomy group and 50.0% in the phaco group at 12 months (P = 0.021). No significant complication was observed in either group.

Conclusions and Relevance

Combined goniotomy and cataract surgery showed a significantly greater reduction in IOP and number of medications compared to cataract surgery alone at 1 year after surgery, with similarly favourable safety profiles.
Ventricular assist device‐related infections and solid organ transplantation—Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice
Authors: Koval Christine E. , Stosor Valentina ,   the AST ID Community of Practice
Published: March 2019

The Infectious Diseases Community of Practice of the American Society of Transplantation has published evidenced‐based guidelines on the prevention and management of infectious complications in SOT recipients since 2004. This updated guideline reviews the epidemiology of ventricular assist device (VAD) infections and provides recommendations for the management and prevention of these infections. Almost one half of those awaiting heart transplantation are supported with VADs. Despite advances in device technologies, VAD infections commonly complicate mechanical circulatory support and remain typified by common components and anatomic locations. These infections have important implications for transplant candidates, most notably increased wait‐list mortality. Strategic management of these infections is crucial for successful transplantation. Coincidentally, explantation of all VAD components at the time of transplantation is often the definitive cure for the device‐associated infection. Highlighted in this updated guideline is the reported success of transplantation in patients with a variety of pre‐existing VAD infections and guidance on post‐transplant management strategies.
Recovery of the Xenopus laevis heart from ROS‐induced stress utilizes conserved pathways of cardiac regeneration
Authors: Jewhurst Kyle , McLaughlin Kelly A.
Published: March 2019

Urodele amphibians and some fish are capable of regenerating up to a quarter of their heart tissue after cardiac injury. While many anuran amphibians like Xenopus laevis are not capable of such feats, they are able to repair lesser levels of cardiac damage, such as that caused by oxidative stress, to a far greater degree than mammals. Using an optogenetic stress induction model that utilizes the protein KillerRed, we have investigated the extent to which mechanisms of cardiac regeneration are conserved during the restoration of normal heart morphology post oxidative stress in X. laevis tadpoles. We focused particularly on the processes of cardiomyocyte proliferation and dedifferentiation, as well as the pathways that facilitate the regulation of these processes. The cardiac response to KillerRed‐induced injury in X. laevis tadpole hearts consists of a phase dominated by indicators of cardiac stress, followed by a repair‐like phase with characteristics similar to mechanisms of cardiac regeneration in urodeles and fish. In the latter phase, we found markers associated with partial dedifferentiation and cardiomyocyte proliferation in the injured tadpole heart, which, unlike in regenerating hearts, are not dependent on Notch or retinoic acid signaling. Ultimately, the X. laevis cardiac response to KillerRed‐induced oxidative stress shares characteristics with both mammalian and urodele/fish repair mechanisms, but is nonetheless a unique form of recovery, occupying an intermediate place on the spectrum of cardiac regenerative ability. An understanding of how Xenopus repairs cardiac damage can help bridge the gap between mammals and urodeles and contribute to new methods of treating heart disease.
Insulin therapy in organ donation and transplantation
Authors: Shapey Iestyn M. , Summers Angela , Yiannoullou Petros , Bannard‐Smith Jonathan , Augustine Titus , Rutter Martin K. , van Dellen David
Published: March 2019

Hyperglycaemia is common in hospitalized individuals, and is often caused by physiological stress associated with critical illness or major surgery. Insulin therapy is an established treatment for hyperglycaemia and acute hyperkalaemia, and has also been used for myocardial dysfunction resistant to inotropic support. Insulin is commonly used in both organ donors and transplant recipients for hyperglycaemia, but the underlying knowledge base supporting its use remains limited. Insulin therapy plays an important yet poorly understood role in both organ donation and transplantation. Tight glycaemic control has been extensively studied in critical care over the past 15 years; however, this has not yet translated into the field of transplantation, where patients are more unwell and where improved outcomes remain an ongoing challenge. Insulin therapy and optimization of glycaemic control represent important areas for future hypothesis‐driven research into organ donation and transplantation, such as amelioration of ischaemia‐reperfusion injury, rejection and infection.
Contest dynamics for food and reproductive resources are defined by health condition in a dung beetle
Authors: Salomão Renato Portela , Favila Mario E. , González‐Tokman Daniel , Chamorro‐Florescano Ivette Alicia
Published: March 2019

Male dung beetles compete to obtain food and females, and early resource recognition and appropriation increase the probability of mating. The outcome of such encounters is expected to be defined by self‐ and the opponent’s health condition. In this study, we analyzed the effect of body condition and immune defense on the contest dynamics between males that rolled a food ball with a partner female (owner males) and intruder males of dung beetle Canthon cyanellus. Body condition was measured as body size, body dry mass, lipid mass, and muscle mass; immune defense was estimated via phenoloxidase activity. Owner males with higher lipid mass contacted the food ball significantly earlier than owner males with lower lipid mass. Individuals with lower phenoloxidase activity started to roll food balls earlier than individuals with higher phenoloxidase activity. Owner males that had higher body dry mass, compared to female partners, began to roll the food ball significantly earlier than male–female pairs with lower differences in dry mass. Heavier males won significantly more contests than lighter males. Our results suggest that the health condition is a key factor related to the dynamics and outcome of male–male contests for resources and females in C. cyanellus. Consequently, differences in individual condition are main determinants of contest outcomes in dung beetles.
U–Pb zircon geochronology of the Hida gneiss and granites in the Kamioka area, Hida Belt
Authors: Takehara Mami , Horie Kenji
Published: March 2019

A new U–Pb dating and oxygen isotope analysis of zircons collected from a granitic mylonite and an undeformed granite in the Kamioka area, in the Hida Belt of southwest Japan, was conducted using a sensitive high‐resolution ion microprobe (SHRIMP) to restrict the timing of the mylonitization in the Funatsu Shear Zone, which is situated on the eastern and southeastern margins of the Hida Belt. Here, undeformed granite intrudes into the granitic mylonite deformed by mylonitization in the Funatsu Shear Zone. The granitic mylonite and the undeformed granite yielded U–Pb zircon ages of 242.6 ±1.9 Ma and 199.1 ±1.9 Ma, respectively. The granitic mylonite and the undeformed granite also yielded zircon oxygen isotope ratios (δ18OVSMOW) of 7.74 ±0.37 ‰ and 5.74 ±0.17 ‰, which suggests that these rocks are derived from different magmas. Therefore, the timing of the mylonitization in the Funatsu Shear Zone is constrained to be at least 242.6–199.1 Ma, which is consistent with other data from the Tateyama area. The U–Pb zircon ages of the banded gneiss in the Kamioka area also reveals that the protolith is a sedimentary rock deposited at approximately 256 Ma, and regional metamorphism occurred at 245.0 ±6.6 Ma, which indicates that the mylonitization in the Funatsu Shear Zone occurred after the metamorphism in the Hida Belt. These geochronological and geochemical data give new insight into the relationship between the Hida Belt and the eastern margin of the Asian continent: the geochronological and geochemical data in this study support the possibility that the Funatsu Shear Zone is comparable with the Cheongsan Shear Zone located at the center of the Ogcheon Belt on the Korean Peninsula.
On cross‐linguistic variation and measures of linguistic complexity in learner texts: Italian, French and English
Authors: Bernardini Petra , Granfeldt Jonas
Published: March 2019

The paper investigates possible effects of cross‐linguistic variation on measures of syntactic complexity in 60 texts from Swedish L1 learners of English, French and Italian as foreign languages at CEFR level A and CEFR level B. A previous study on the same learners and texts, showed significant differences between proficiency levels for two length measures of complexity in English and French, but not in Italian. In this paper we hypothesize that due to the Null Subject property of Italian, the developmental prediction for some complexity measures might be different in Italian compared to French and English. In fact, previous research has suggested that beginner learners of Italian overuse overt subjects which might lead to higher scores, relatively speaking, of length measures in Italian at the lowest levels of proficiency. However, contrary to our hypothesis, we did not find more Null subjects at CEFR level B than at CEFR level A, but we did find clear restrictions on their distribution. We conclude that we are a long way from understanding how cross‐linguistic differences interact with other variables such as tasks and language combinations and what the effects might be on measures of syntactic complexity.
Low‐temperature sintering of BF‐PT‐BZ ternary solid solutions with enhanced piezoelectric properties
Authors: Luo Feng , Guan Haowen , Peng Rui , Jian Jie , Chen Jianguo , Cheng Jinrong
Published: March 2019

The 0.34BiFeO3‐0.46PbTiO3‐0.2BaZrO3 (BF‐PT‐0.2BZ) ternary solid solutions were prepared by the solid‐state reaction methods. Different amounts of Li2CO3‐Bi2O3 (LB) additives were introduced into the based materials after the calcination process. Upon using LB additives, the sintering temperature of BF‐PT‐0.2BZ ceramics was lowered to 950°C, while the relative density was enhanced to the highest of about 97% for LB of 1 wt%. XRD results indicate that BF‐PT‐0.2BZ ceramics exhibit the perovskite structure without detectable second phases. SEM images reveal that BF‐PT‐0.2BZ ceramics are well densified and the grain size is enhanced with the addition of LB. Moreover, the piezoelectric properties are enhanced significantly, achieving the highest d33 and bipolar strain of 350 pC/N and 0.53%, respectively, for BF‐PT‐0.2BZ ceramics with LB of 1 wt%. Our results indicate that low‐temperature sintered BF‐PT‐0.2BZ ceramics with excellent piezoelectric properties have promising applications in multilayer piezoelectric actuators.
Evaluation of cutaneous adverse events of encorafenib and binimetinb: COMMENT on article by Graf et al.
Authors: Livingstone E.
Published: March 2019

Linked article: This is a commentary on N.P. Graf et al., pp. 686–692 in this issue. To view this article visit https://doi.org/10.1111/jdv.15363.
A two‐step immunoblot assay for serological diagnosis of anti‐laminin γ‐1 pemphigoid
Authors: Yamagami J. , Amagai M.
Published: March 2019

Linked article: This is a commentary on F. Solimani et al., pp. 735‐741 in this issue. To view this article visit https://doi.org/10.1111/jdv.15170.
Ageing of the somatosensory system at the periphery: age‐related changes in cutaneous mechanoreceptors
Authors: García‐Piqueras Jorge , García‐Mesa Yolanda , Cárcaba Lucia , Feito Jorge , Torres‐Parejo Isidro , Martín‐Biedma Benjamín , Cobo Juan , García‐Suárez Olivia , Vega Jose A.
Published: March 2019

Decline of tactile sensation associated with ageing depends on modifications in skin and both central and peripheral nervous systems. At present, age‐related changes in the periphery of the somatosensory system, particularly concerning the effects on mechanoreceptors, remain unknown. Here we used immunohistochemistry to analyse the age‐dependent changes in Meissner's and Pacinian corpuscles as well as in Merkel cell‐neurite complexes. Moreover, variations in the neurotrophic TrkB‐BDNF system and the mechanoprotein Piezo2 (involved in maintenance of cutaneous mechanoreceptors and light touch, respectively) were evaluated. The number of Meissner's corpuscles and Merkel cells decreased progressively with ageing. Meissner's corpuscles were smaller, rounded in morphology and located deeper in the dermis, and signs of corpuscular denervation were found in the oldest subjects. Pacinian corpuscles generally showed no relevant age‐related alterations. Reduced expression of Piezo2 in the axon of Meissner's corpuscles and in Merkel cells was observed in old subjects, as well was a decline in the BDNF‐TrkB neurotrophic system. This study demonstrates that cutaneous Meissner's corpuscles and Merkel cell‐neurite complexes (and less evidently Pacinian corpuscles) undergo morphological and size changes during the ageing process, as well as a reduction in terms of density. Furthermore, the mechanoprotein Piezo2 and the neurotrophic TrkB‐BDNF system are reduced in aged corpuscles. Taken together, these alterations might explain part of the impairment of the somatosensory system associated with ageing.