bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibiting Mycobacterium tuberculosis ClpP1P2 by addressing the equatorial handle domain of ClpP1 subunit
Authors: Yang Yang , Zhu Yibo , Yang Tao , Li Tao , Ju Yuan , Song Yingjie , He Jun , Liu Huanxiang , Bao Rui , Luo Youfu
Published: July 2019

Unlike other bacterial ClpP systems, mycobacterial ClpP1P2 complex is essential for mycobacterial survival. The functional details of Mycobacterium tuberculosis (Mtb) ClpP1P2 remains largely elusive and selectively targeting ClpP of different species is a big challenge. In this work, cediranib was demonstrated to significantly decrease the activity of MtbClpP1P2. By solving the crystal structure of cediranib-bound MtbClpP1P2, we found that cediranib dysregulates MtbClpP1P2 by interfering with handle domain of the equatorial region of MtbClpP1, indicating that the inter-ring dynamics are crucial for its function. This finding provides direct evidence for the notion that a conformational switch in the equatorial handle domain is essential for ClpP activity. We also present biochemical data to interpret the distinct interaction pattern and inhibitory properties of cediranib toward MtbClpP1P2. These results suggest that the variable handle domain region is responsible for the species-selectivity of cediranib, which suggests the equatorial handle domain as a potential region for screening pathogen-specific ClpP inhibitors.
Site-directed M2 proton channel inhibitors enable synergistic combination therapy for rimantadine-resistant pandemic influenza
Authors: Scott Claire , Kankanala Jayakanth , Foster Toshana L. , Goldhill Daniel , Simmons Katie , Pingen Marieke , Bentham Matthew , Atkins Elizabeth , Loundras Eleni , Elderfield Ruth , Claridge Jolyon K. , Thompson Joseph , Stilwell Peter R. , Tathineni Ranjitha , McKimmie Clive , Targett-Adams Paul , Schnell Jason R. , Cook Graham , Barclay Wendy S. , Foster Richard , Griffin Stephen
Published: July 2019

Pandemic influenza A virus (IAV) remains a significant threat to global health. Preparedness relies primarily upon a single class of neuraminidase (NA) targeted antivirals, against which resistance is steadily growing. The M2 proton channel is an alternative clinically proven antiviral target, yet a near-ubiquitous S31N polymorphism in M2 evokes resistance to licensed adamantane drugs. Hence, inhibitors capable of targeting N31 containing M2 (M2-N31) are highly desirable.

Rationalin silicodesign andin vitroscreens delineated compounds favouring either lumenal or peripheral M2 binding, yielding effective M2-N31 inhibitors in both cases. Hits included adamantanes as well as novel compounds, with some showing low micromolar potency versus pandemic “swine” H1N1 influenza (Eng195) in culture. Interestingly, a published adamantane-based M2-N31 inhibitor rapidly selected a resistant V27A polymorphism (M2-A27/N31), whereas this was not the case for non-adamantane compounds. Nevertheless, combinations of adamantanes and novel compounds achieved synergistic antiviral effects, and the latter synergised with the neuraminidase inhibitor (NAi), Zanamivir. Thus, site-directed drug combinations show potential to rejuvenate M2 as an antiviral target whilst reducing the risk of drug resistance.
Primate hippocampus size and organization are predicted by sociality but not diet
Authors: Todorov Orlin S. , Weisbecker Vera , Gilissen Emmanuel , Zilles Karl , de Sousa Alexandra A.
Published: July 2019

The hippocampus is well known for its roles in spatial navigation and memory, but it is organized into regions that have different connections and functional specializations. Notably, the region CA2 has a role in social and not spatial cognition, as is the case for the regions CA1 and CA3 that surround it. Here we investigated the evolution of the hippocampus in terms of its size and organization in relation to the evolution of social and ecological variables in primates, namely home range, diet and different measures of group size. We found that the volumes within the whole cornu ammonis coevolve with group size, while only the volume of CA1 and subiculum can also be predicted by home range. On the other hand, diet, expressed as a shift from folivory toward frugivory, was shown to not be related to hippocampal volume. Interestingly, CA2 was shown to exhibit phylogenetic signal only against certain measures of group size but not with ecological factors. We also found that sex differences in the hippocampus are related to body size sex dimorphism. This is in line with reports of sex differences in hippocampal volume in non-primates that are related to social structure and sex differences in behaviour. Our findings support the notion that in primates, the hippocampus is a mosaic structure evolving in line with social pressures, where certain subsections evolve in line with spatial ability too.
The moderating role of tenure on the effects of job insecurity and employability on turnover intentions and absenteeism
Authors: León Federico R. , Morales Oswaldo
Published: July 2019

Purpose

The purpose of this paper is to provide evidence on the role of tenure as a moderator of the effects of job insecurity (JI) and employability on turnover intentions and absenteeism and will demonstrate its importance in personnel research and theorization.

Design/methodology/approach

Data from a sample of client service representatives of a Peruvian call centre (n=268) were analysed. Tests of hypotheses targeted the intact group as a whole and divided into short (3–10 months), medium (11–14 months) and long job tenure groups (15–37 months).

Findings

Results of general linear models revealed that the effects of JI on turnover intention observed in the intact group were aligned with those seen within each of the tenure groups. However, this was not the case for the effects of JI on absenteeism or the effects of employability on turnover intention and absenteeism. A comparison of results of various regression models indicated that the effects of JI and employability on absenteeism differed in meaningful ways across the intact group and the tenure groups.

Research limitations/implications

The evidence does not reveal whether the observed differences stem from dynamic personnel selection processes or whether they express different relationships between the variables at various stages of an employee’s trajectory in an organization.

Practical implications

Human resource managers at call centres will be stimulated to re-evaluate the costs and benefits of promoting tenure, and journal editors will have to consider requesting the inclusion of tenure as a variable in studies focussing on organizations with high turnover.

Originality/value

This study is the first to prove that the effects of JI and employability on turnover intention and absenteeism vary across job tenure levels. It also shows the importance of addressing tenure in personnel research and theorization.
Effect of halal awareness, halal logo and attitude on foreign consumers’ purchase intention
Authors: Bashir Abdalla Mohamed
Published: July 2019

Purpose

The purpose of this paper is to determine the factors that affect foreign consumers’ purchase intention towards purchasing halal food products in South Africa. These factors are halal awareness, halal logo and attitude, which are important factors in affecting the intention of consumers.

Design/methodology/approach

Data were collected via a self-questionnaire with a sample of 230 foreign consumers. For analysing these data, a structural equation modelling technique was used in this study.

Findings

Based on the study’s results, all factors significantly influence foreign consumers’ intention towards purchasing halal food products and, subsequently, their buying behaviour. Interestingly, the study found that attitudes and halal awareness of non-Muslim consumers are very high compared with those of the Muslim consumers. Although the study addressed halal food consumers, most of the respondents participated in the study were non-Muslims and the majority of them were Christians.

Research limitations/implications

The respondents were only limited to the Cape Town city in South Africa, and the focus was only on five variables related to halal food consumers, namely, halal awareness halal logo, attitude, purchase intention and buying behaviour.

Social implications

This study can be used to develop halal food products to attract both Muslim and non-Muslim consumers, who are foreigners to a particular country.

Originality/value

This study is one of the first studies seeking to determine the factors that affect foreign consumers with regard to the purchase of halal food products in South Africa. It is regarded one of the first attempts to determine halal awareness, halal logo and attitude and how purchase intention and buying behaviour can be influenced.
Urban households’ willingness to pay for milk safety in Samsun and Trabzon provinces of Turkey
Authors: Bozoglu Mehmet , Bilgic Abdulbaki , Huang Chung L. , Florkowski Wojciech J. , Topuz Bakiye Kilic
Published: July 2019

Purpose

The purpose of this paper is to examine urban households’ willingness to pay (WTP) for milk safety and to analyze the factors affecting WTP premiums using data obtained from surveys conducted in Samsun and Trabzon provinces, Turkey.

Design/methodology/approach

Contingent valuation and censoring methods including the error-dependent bivariate Heckman SS model were used for estimating WTP for milk safety and its effective factors, respectively.

Findings

The study indicates that 68 percent of the households were willing to pay 0.35 per liter for improving the safety of milk. The model results show that satisfaction with food safety standards, being married and full-time employment have statistically significant positive effects on the WTP for ISO-certified milk. However, purchasing milk from farmers or open-air markets, age, having a child six-year old or younger, and high school or higher education have statistically significant negative effects on the WTP for ISO-certified milk.

Research limitations/implications

The main limitation of the current study is that only urban consumers’ WTP and effective factors for milk safety were examined in two provinces of Turkey.

Practical implications

More rigorous implementations of food safety standards, traceability systems and effective educational campaigns could promote households’ food safety awareness and increase their demand for milk safety.

Social implications

Knowing what factors are involved in consumer WTP is extremely important for decision makers to create new social policies in the region or country.

Originality/value

A similar study has not been conducted in Turkey. The novelty of this study is the specification and robust estimation of three different but competing models to reveal the wide range of WTP amounts for safe milk.
A novel variant of the H-Φ field formulation for magnetostatic and eddy current problems
Authors: Smajic Jasmin
Published: July 2019

Purpose

The paper presents a new variant of the H-Φ field formulation for solving 3-D magnetostatic and frequency domain eddy current problems. The suggested formulation uses the vector and scalar tetrahedral elements within conducting and non-conducting domains, respectively. The presented numerical method is capable of solving multiply connected regions and eliminates the need for computing the source current density and the source magnetic field before the actual magnetostatic and eddy current simulations. The obtained magnetostatic results are verified by comparison against the corresponding results of the standard stationary current distribution analysis combined with the Biot-Savart integration. The accuracy of the eddy current results is demonstrated by comparison against the classical A-A-f approach in frequency domain.

Design/methodology/approach

The theory and implementation of the new H-Φ magnetostatic and eddy current solver is presented in detail. The method delivers reliable results without the need to compute the source current density and source magnetic field before the actual simulation.

Findings

The proposed H-Φ produce radically smaller and considerably better conditioned equation systems than the alternative A-A approach, which usually requires the unphysical regularization in terms of a low electric conductivity value within the nonconductive domain.

Originality/value

The presented numerical method is capable of solving multiply connected regions and eliminates the need for computing the source current density and the source magnetic field before the actual magnetostatic and eddy current simulations.
Are high-performance work systems (HPWS) appreciated by everyone? The role of management position and gender on the relationship between HPWS and affective commitment
Authors: Andersén Jim , Andersén Annelie
Published: July 2019

Purpose

Although most studies on HPWS focus on various firm-level outcomes, there has been an increasing interest in how employees are affected by HPWS. However, most of these studies use social exchange theory and, based on an idea of reciprocal exchange, implicitly assume that all employees become more affectively committed to organizations using HPWS. Based on social identity theory, the authors argue that management position and gender likely influence how individuals respond to HPWS. Thus, the purpose of this paper is to examine how HPWS affects AC among managers, subordinates, men and women.

Design/methodology/approach

Hierarchical linear model analysis of 356 employees in 26 Swedish small- and medium-sized manufacturing companies.

Findings

In the sample examined, managers and women show increased affective commitment (AC) in organizations using HPWS. For men with non-managerial positions, the results indicate a reversed relationship, i.e. HPWS could actually reduce AC.

Originality/value

The findings indicate the need to consider individual differences when examining the effect of HPWS, and highlight the usefulness of relational-oriented theories when studying the employee outcomes of HRM-systems.
Expanding repertoires of resistance
Authors: Taylor Kara Michelle , Taylor Evan M. , Hartman Paul , Woodard Rebecca , Vaughan Andrea , Coppola Rick , Rocha Daniel J. , Machado Emily
Published: July 2019

Purpose

This paper aims to examine how a collaborative narrative inquiry focused on cultivating critical English Language Arts (ELA) pedagogies supported teacher agency, or “the capacity of actors to critically shape their own responsiveness to problematic situations” (Emirbayer and Mische, 1998, p. 971).

Design/methodology/approach

Situated in a semester-long inquiry group, eight k-16 educators used narrative inquiry processes (Clandinin, 1992) to write and collectively analyze (Ezzy, 2002) stories describing personal experiences that brought them to critical ELA pedagogies. They engaged in three levels of analysis across the eight narratives, including open coding, thematic identification, and identification of how the narrative inquiry impacted their classroom practices.

Findings

Across the narratives, the authors identify what aspects of the ELA reading, writing and languaging curriculum emerged as problematic; situate themselves in systems of oppression and privilege; and examine how processes of critical narrative inquiry contributed to their capacities to respond to these issues.

Research limitations/implications

Collaborative narrative inquiry between teachers and teacher educators (Sjostrom and McCoyne, 2017) can be a powerful method to cultivate critical pedagogies.

Practical implications

Teachers across grade levels, schools, disciplines and backgrounds can collectively organize to cultivate critical ELA pedagogies.

Originality/value

Although coordinated opportunities to engage in critical inquiry work across k-16 contexts are rare, the authors believe that the knowledge, skills and confidence they gained through this professional inquiry sensitized them to oppressive curricular norms and expanded their repertoires of resistance.
From emotional labor to customer loyalty in hospitality
Authors: Wang Chung-Jen
Published: July 2019

Purpose

The purpose of this study was based on the job demands -resources model (Bakker et al., 2004) and conservation of resources theory (Hobfoll, 1989) by using three levels of variables, namely, company (i.e., perceived organizational support), department (i.e., abusive supervision), and employee (i.e., deep acting, surface acting, and self-efficacy) levels, to investigate its interactions with contextual influences on service quality and its linkage with customer loyalty.

Design/methodology/approach

A three-level hierarchical linear model was examined in research settings by using a dyadic data set of 1,082 service employees and customers in international tourist hotels.

Findings

Findings revealed that deep acting relates positively to service quality, surface acting relates negatively to service quality, and service quality relates positively to customer loyalty. For the three-level interactions, the positive relationship between deep acting and service quality was strengthened by perceived organizational support (POS) and self-efficacy but weakened by abusive supervision. By contrast, the negative relationship between surface acting and service quality was mitigated by POS and self-efficacy but exacerbated by abusive supervision.

Originality/value

Given the importance of emotional labor research in the hospitality industry, the current study contributes to the areas of service quality and customer loyalty and suggests future directions for hospitality research.
FGM in Egypt between socio-cultural barriers and lack of political will
Authors: Khodary Yasmin , Hamdy Nehal
Published: July 2019

Purpose

This study aims to detect the main factors impeding the anti-female genital mutilation (FGM) efforts in Egypt post the January 25 revolution, with a special focus on the era of president El-Sisi. The purpose of this paper is to explain the reasons behind the continuation of violence against women in Egypt, namely, FGM, in light of the patriarchal structures and the state willingness to address that challenge.

Design/methodology/approach

The study utilizes a qualitative methodology. The study embarks on in-depth semi-structured interviews with 23 participants who experienced FGM and nine key informants from medical, religious, political and civil society backgrounds, including a professor of pathology, a gynecologist, a diplomatic researcher in Al-Azhar, three members of parliament, a representative of the Ministry of Population, the reporter of the National Council for Women and a representative of Nazra non-governmental organization for feminist studies in Egypt.

Findings

The findings reveal that FGM remains prevalent not only due to the persisting socio-cultural context that continues to embrace and reproduces gender inequalities, but also because of the insufficient political will to combat FGM and enforce the required laws.

Social implications

FGM is considered one form of gender inequality perpetuated by social, cultural and economic structures. It is recognized internationally as a crime and a violation against women’s rights as per the Universal Declaration of Human Rights, the Convention on the Elimination of All Forms of Discrimination against Women, the Convention on the Rights of the Child, etc. Although the Egyptian Government passed laws banning the practice of FGM, it continues to form a challenging problem to social workers, women activists, human rights groups and public health officials.

Originality/value

Little work has been done to investigate FGM post the January 25 revolution in Egypt and identify the main factors impeding the anti-FGM efforts in Egypt. This work fills this gap and concludes with some lessons learnt to fight FGM and improve the anti-FGM efforts.
Leveraging learning analytics for student reflection and course evaluation
Authors: Ozdemir Devrim , Opseth Heather M. , Taylor Holland
Published: July 2019

Purpose

The purpose of this paper is to demonstrate a process of faculty utilization of learning analytics by evaluating students’ course objective achievement results to enable student reflection, student remediation and faculty curriculum evaluation.

Design/methodology/approach

Upon the completion of a backward curriculum design process, the authors utilized learning analytics to improve advising, student reflection, remediation and curriculum evaluation. The learning management system incorporated the learning analytics tool to assist the learning analytics process. The course faculty, student advisors and students utilized the learning analytics throughout the academic year.

Findings

Unlike relying merely on student grades and other proxy indicators of learning, the learning analytics tool provided immediate and direct data to multiple stakeholders for advising, student reflection, student remediation and course curriculum evaluation. The authors believe it was a meaningful endeavor. It enabled meaningful conversations focusing on course learning objectives and provided detailed information on each student. The learning analytics tool also provided detailed information regarding which areas faculty needed to improve in the curriculum.

Originality/value

Most of the literature on learning analytics present the cases that administrators utilized learning analytics to make higher level decisions and researchers to explore the factors involved in learning. This paper provides cases to faculty regarding how learning analytics can benefit the faculty and the students.
The potential for civic engagement of older persons in the ageing society of Thailand
Authors: Tangchonlatip Kanchana , Chamratrithirong Aphichat , Lucktong Aksarapak
Published: July 2019

Purpose

Several studies revealed the importance of older persons’ contribution to society. The enhancement of their potential to engage in civic activities should be encouraged. The purpose of this paper is to investigate factors associated with their civic engagement potential.

Design/methodology/approach

Data are from Thailand’s National Survey of Older Persons conducted by the National Statistical Office in 2011. A sample of 24,433 persons aged 60 years or older was analyzed to assess their engagement in four community activities. The data were subjected to logistic regression analysis.

Findings

This study found that the readiness and willingness to engage in socially productive activities of Thai older persons ranged from 7 to 23 percent depending on type of activities. The factors of ageing health, confidence in their family’s ability to assist them, and satisfaction with government services were significantly associated with their readiness and willingness to engage in socially productive activities. Inadequacy of income was not found to be an obstructing factor toward their readiness and willingness to engage in civic life in general, it inhibited only the sharing of knowledge and skills with others.

Originality/value

The findings reflect the impact of internal constraining factors and external enhancing factors on engagement of Thai older persons in civic activities. Policy implications on the role of the government to promote active ageing are discussed.
Halal certification or ingredient disclosure
Authors: Takeshita Shuko
Published: July 2019

Purpose

The purpose of this study is to clarify what is really needed to attract Muslim tourists by comparing the two main approaches to serving food with halal certification or with ingredient disclosure.

Design/methodology/approach

This research adopted a comparative analysis of a Group promoting “halal certification” and a Group promoting “ingredient disclosure” mainly from the tourists’ perspective. Taito Ward, Tokyo, encourages restaurants to obtain halal certification, while the approach of Takayama City is to disclose the ingredients. The study compares the advantages and disadvantages of these two approaches and also investigates factors influencing them.

Findings

This study revealed that Muslim tourists would like to see both halal certification and ingredient disclosure. The reason why Taito Ward and Takayama City pursue different strategies can be summarized in three points: the types of food offered in the two areas, the vastly different scales of the two areas as tourist destinations and the different perspectives of their respective advisors.

Research limitations/implications

The limitations of this study include the small sample size and the low diversity of the origins of Muslim tourists. However, this research is still significant because few academic studies on halal certification have been done from the tourists’ perspective.

Originality/value

There are many things that could be done to attract Muslim tourists. Even without halal certification, there are many restaurants that can cater to Muslims in Japan. A little consideration and thoughtfulness on the part of restaurants can enhance the probability of attracting Muslim tourists.
A Fatal Case of Poisoning with Fentanyl Transdermal Patches in Japan
Authors: Nara Akina , Yamada Chiho , Saka Kanju , Kodama Takanori , Yoshida Masaki , Iwahara Kaori , Takagi Tetsuya
Published: July 2019

Fentanyl transdermal patches have been used to treat cancer‐ and noncancer‐related chronic pain. However, its inappropriate or illegal application may cause fatal poisoning. We herein present the case of a Japanese woman in her 40s who was found dead with seven 25‐μg/h fentanyl transdermal patches on her body. We established a detailed toxicological analysis procedure to quantify fentanyl, and its metabolite norfentanyl, and other drugs (acetaminophen, allylisopropylacetylurea, celecoxib, estazolam, promethazine, and sertraline) in human whole blood by ultra‐high‐performance liquid chromatography–tandem mass spectrometry. The measured fentanyl and norfentanyl concentrations in the femoral and cardiac blood were 0.051 and 0.072 μg/mL and 0.033 and 0.076 μg/mL, respectively. The decedent's fentanyl concentrations were consistent with previously reported postmortem blood levels for fatal cases of poisoning by fentanyl transdermal patches. Based on the decedent's case history, autopsy findings, and toxicological analyses, the cause of death was identified as intoxication with transdermal fentanyl.
Causal effect of alcohol consumption on hyperuricemia using a Mendelian randomization design
Authors: Jee Yon Ho , Jung Keum Ji , Park Yong‐Beom , Spiller Wes , Jee Sun Ha
Published: July 2019

Aim

We used a Mendelian randomization analysis to assess the causal effect of alcohol consumption on hyperuricemia in Koreans.

Methods

The Korean Cancer Prevention Study‐II (KCPS‐II) Biobank cohort consisted of 156 701 healthy Korean aged 20 years or older. Clinical data including serum uric acid, alcohol consumption, and other related confounding variables were collected at baseline. The 27 single nucleotide polymorphisms (SNP) including rs671 in aldehyde dehydrogenase 2 (ALDH2) were obtained from a genome‐wide association study of alcohol consumption in the KCPS‐II Biobank among 11 678 men and women in 2017. Both unweighted and weighted genetic risk score (wGRS) were calculated using 10 SNPs selected based on linkage disequilibrium.

Results

As strong instrumental variables, both rs671 and wGRS were associated with an increased amount of alcohol drinking in men and women. Alcohol consumption was also positively associated with hyperuricemia risk in men (P < .001) and women (P = .014). Both rs671 major G allele and wGRS were not associated with hyperuricemia. In Mendelian randomization analysis, the causal relationship between any alcohol consumption and hyperuricemia was found only in men, albeit non‐significant after correction for multiple testing. The associations did not change after excluding heavy drinkers or the elderly.

Conclusions

These results provide evidence that alcohol consumption is causally associated with risk of hyperuricemia in Korean men and support its role as a risk determinant.
Combining the 5.8S and ITS2 to improve classification of fungi
Authors: Heeger Felix , Wurzbacher Christian , Bourne Elizabeth C. , Mazzoni Camila J. , Monaghan Michael T.
Published: July 2019

The internal transcribed spacer (ITS) is used often in DNA metabarcoding of fungi. One disadvantage of its high variability may be a failure to classify operational taxonomic units (OTUs) when no similar reference sequence exists. We tested whether the 5.8S region, often sequenced with ITS2 but discarded before analysis, could provide OTU classifications when ITS2 fails.

We used in silico evaluation to compare classification success of 5.8S and ITS2 from the UNITE database when reference sequences of the same species, genus, or family were removed. We then developed an automated pipeline for a combined 5.8S–ITS2 analysis and applied it to mixed environmental samples containing many lineages that are underrepresented in databases.

ITS was clearly superior for species‐level classifications with a complete reference database, but 5.8S outperformed ITS at higher level classifications with an incomplete database. Our combined 5.8S‐ITS2 pipeline classified 3× more fungal OTUs compared to ITS2 alone, particularly within Chytridiomycota (27×) and Rozellomycota (6×).

Missing reference sequences led to the failure of ITS to classify many fungal OTUs at all, and to a significant underestimation of environmental fungal diversity. Using 5.8S to complement ITS classification will likely provide better estimates of diversity in lineages for which database coverage is poor.
Basolateral amygdala is required for reconsolidation updating of heroin‐associated memory after prolonged withdrawal
Authors: Yuan Kai , Cao Lu , Xue Yan‐Xue , Luo Yi‐Xiao , Liu Xiao‐Xing , Kong Fan‐Ni , Tabarak Serik , Liao Fan , Meng Shi‐Qiu , Han Ying , Wu Ping , Bao Yan‐Ping , Zhang Wen , Lu Lin , Shi Jie
Published: July 2019

Postretrieval extinction procedures are effective nonpharmacological interventions for disrupting drug‐associated memories. Nonetheless, the conditioned stimulus (CS) memory retrieval‐extinction procedure is ineffective in inhibiting drug craving and relapse after prolonged withdrawal, which significantly undermines its therapeutic potential. In the present study, we showed that, unlike the CS memory retrieval‐extinction procedure, noncontingent heroin injections (unconditioned stimulus [UCS]) 1 hour before the extinction sessions decreased the heroin‐priming‐induced reinstatement, renewal, and spontaneous recovery of heroin seeking after 28 days of withdrawal (ie, remote heroin‐associated memories) in rats. The UCS retrieval manipulation induced reactivation of the basolateral amygdala (BLA) after prolonged withdrawal, and this reactivation was absent with the CS retrieval manipulation. Chemogenetic inactivation of the BLA abolished the inhibitory effect of the UCS memory retrieval‐extinction procedure on heroin‐priming‐induced reinstatement after prolonged withdrawal. Furthermore, the combination of chemogenetic reactivation of BLA and CS retrieval‐extinction procedure resembled the inhibitory effect of UCS retrieval‐extinction procedure on heroin seeking after prolonged withdrawal. We also observed that the inhibitory effect of the UCS retrieval‐extinction procedure is mediated by regulation of AMPA receptor endocytosis in the BLA. Our results demonstrate critical engagement of the BLA in reconsolidation updating of heroin‐associated memory after prolonged withdrawal, extending our knowledge of the boundary conditions of the reconsolidation of drug‐associated memories.
CYP2B6 Genotype‐Dependent Inhibition of CYP1A2 and Induction of CYP2A6 by the Antiretroviral Drug Efavirenz in Healthy Volunteers
Authors: Metzger Ingrid F. , Dave Nimita , Kreutz Yvonne , Lu Jessica B.L. , Galinsky Raymond E. , Desta Zeruesenay
Published: July 2019

We investigated the effect of efavirenz on the activities of cytochrome P450 (CYP)1A2, CYP2A6, xanthine oxidase (XO), and N‐acetyltransferase 2 (NAT2), using caffeine as a probe. A single 150 mg oral dose of caffeine was administered to healthy volunteers (n = 58) on two separate occasions; with a single 600 mg oral dose of efavirenz and after treatment with 600 mg/day efavirenz for 17 days. Caffeine and its metabolites in plasma and urine were quantified using liquid chromatography/tandem‐mass spectrometry. DNA was genotyped for CYP2B6*4 (785A>G), CYP2B6*9 (516G>T), and CYP2B6*18 (983T>C) alleles using TaqMan assays. Relative to single‐dose efavirenz treatment, multiple doses of efavirenz decreased CYP1A2 (by 38%) and increased CYP2A6 (by 85%) activities (P < 0.05); XO and NAT2 activities were unaffected. CYP2B6*6*6 genotype was associated with lower CYP1A2 activity following both single and multiple doses of efavirenz. No similar association was noted for CYP2A6 activity. This is the first report showing that efavirenz reduces hepatic CYP1A2 and suggesting chronic efavirenz exposure likely enhances the elimination of CYP2A6 substrates. This is also the first to report the extent of efavirenz–CYP1A2 interaction may be efavirenz exposure‐dependent and CYP2B6 genotype‐dependent.
Pregnancy‐associated plasma protein‐A2 levels are increased in early‐pregnancy gestational diabetes: a novel biomarker for early risk estimation
Authors: Dereke J. , Nilsson C. , Strevens H. , Landin‐Olsson M. , Hillman M.
Published: July 2019

Aim

To determine whether pregnancy‐associated plasma protein‐A2 levels are increased in early pregnancies complicated by gestational diabetes and whether gestation age influences levels. The possible use of pregnancy‐associated plasma protein‐A2 as a pre‐screening biomarker to reduce the need for performing oral glucose tolerance tests in pregnant women was also investigated.

Methods

Pregnant women were diagnosed with gestational diabetes in early pregnancy after a 2‐hour 75 g oral glucose tolerance test in the catchment area of Skåne University Hospital, Lund, Sweden during 2011–2015 (n = 99). Age‐ and BMI‐matched pregnant women without diabetes were recruited at similar gestational ages from maternal healthcare centres in the same geographical area during 2014–2015 to act as controls (n = 100). Circulating pregnancy‐associated plasma protein‐A2 was analysed in participant serum using commercially available enzyme‐linked immunosorbent assay kits.

Results

Circulating pregnancy‐associated plasma protein‐A2 was increased in women diagnosed with gestational diabetes [13.5 (9.58–18.8) ng/ml] compared with controls [8.11 (5.74–11.3) ng/ml; P < 0.001]. Pregnancy‐associated plasma protein‐A2 was associated with gestational diabetes independent of age, BMI, C‐peptide and adiponectin (P < 0.001). Pregnancy‐associated plasma protein‐A2 as a pre‐screening biomarker to identify women at a decreased risk of gestational diabetes resulted in a negative predictive value of 99.7%, with a sensitivity of 96% and a specificity of 30% at a cut‐off level of 6 ng/ml.

Conclusions

This is the first study to show increased pregnancy‐associated plasma protein‐A2 levels in gestational diabetes. Pregnancy‐associated plasma protein‐A2 also shows promise as a pre‐screening biomarker with the potential to reduce the need for performing oral glucose tolerance tests in early pregnancy. Future prospective cohort studies in a larger group of both high‐ and low‐risk women are, however, needed to further confirm this observation.
Nonalcoholic fatty liver disease increases the risk of gastroesophageal reflux disease: A systematic review and meta‐analysis
Authors: Xue Jinru , Xin Hua , Ren Na , Zhou Changyu , Yang Jinghui , Song Lina , Qin Shaoyou
Published: July 2019

Background

Increasing evidence indicates that nonalcoholic fatty liver disease (NAFLD) is linked to an increased risk of extra‐hepatic conditions. However, it is currently uncertain whether NAFLD is associated with the risk of gastroesophageal reflux disease (GERD). We performed a systematic review and meta‐analysis of relevant studies to examine the association between NAFLD and the risk of GERD.

Methods

We searched PubMed, Scopus, Embase and Web of Science from 1 January 1975 to 15 December 2018, using predefined terms to identify cross‐sectional, case‐control and cohort studies investigating the association between NAFLD and GERD.

Results

Nine observational studies involving 185 118 subjects were eligible for inclusion in the meta‐analysis. Overall, NAFLD was significantly associated with an increased risk of GERD (random effect OR 1.28; 95% CI: 1.12‐1.44, I2 = 82%). Moreover, the significant association between NAFLD and GERD was consistent both for studies with adjusted OR/HR (n = 6, random effect OR = 1.16, 95% CI: 1.03‐1.30) and those with unadjusted OR/HR (n = 3, random effect OR = 2.09, 95% CI: 1.62‐2.56) as measures of effect. Both funnel plot and Egger's test suggested the existence of publication bias. However, a sensitivity analysis by sequentially omitting each study did not alter the pooled outcome,suggesting the robustness of the association.

Conclusion

NAFLD is associated with an increased risk of GERD. However, future large and cohort studies are still needed to determine the causal relationship between NAFLD and the risk of GERD.
The role of the nucleus accumbens in learned approach behavior diminishes with training
Authors: Dobrovitsky Veronica , West Mark O. , Horvitz Jon C.
Published: July 2019

Nucleus accumbens dopamine plays a key role in reward‐directed approach. Past findings suggest that dopamine's role in the expression of learned behavior diminishes with extended training. However, little is known about the central substrates that mediate the shift to dopamine‐independent reward approach. In the present study, rats approached and inserted the head into a reward compartment in response to a cue signaling food delivery. On days 4 and 5 of 28‐trial‐per‐day sessions, D1 receptor antagonist R(+)‐7‐chloro‐8‐hydroxy‐3‐methyl‐1‐phenyl‐2,3,4,5‐tetrahydro‐1H‐3‐benzazepine hydrochloride (SCH23390) infused to the NAc core reduced the probability and speed of cued approach. The disruptive effect of D1 receptor blockade was specific to the nucleus accumbens core and not seen with drug infusions to nearby dopamine target regions. In rats that received drug infusions after extended training (days 10 or 11), accumbens core D1 receptor blockade produced little effect on the expression of the same behavior. These results could have been due to a continued accumbens mediation of cued approach even after the behavior had become independent of accumbens D1 receptors. However, accumbens core ionotropic glutamate receptor blockade disrupted cued approach during early but not late stages of training, similar to the effects of D1 antagonist infusions. The results suggest that with extended training, a nucleus accumbens D1‐dependent behavior becomes less dependent not only on nucleus accumbens D1 transmission but also on excitatory transmission in the nucleus accumbens. These findings fill an important gap in a growing literature on reorganization of striatal function over the course of training.
Volatile anesthetic sevoflurane pretreatment alleviates hypoxia‐induced potentiation of excitatory inputs to striatal medium spiny neurons of mice
Authors: Fukuda Masataka , Ando Nozomi , Sugasawa Yusuke , Inoue Ritsuko , Nakauchi Sakura , Miura Masami , Nishimura Kinya
Published: July 2019

Sevoflurane, a commonly used anesthetic in surgery, has drawn attention because of its preconditioning effects in hypoxic conditions. To investigate the preconditioning effects in the striatum, a common site for ischemic stroke, we collected whole‐cell current‐clamp recordings from striatal medium spiny neurons. In our in vitro brain slice experiments, deprivation of oxygen and glucose depolarized the striatal neurons to subthreshold potentials, and the pre‐administration of sevoflurane (4%, 15 min) prolonged the time to depolarization. Furthermore, transient hypoxia induced the potentiation of excitatory postsynaptic potentials, which play a part in post‐ischemic excitotoxicity. Glibenclamide, a KATP channel inhibitor, reversed the prolonged time to depolarization and the prevention of the pathological potentiation of excitatory responses, indicating that the short exposure to sevoflurane likely participates in neuroprotection against hypoxia via activation of KATP channels. A monocarboxylate transporter blocker, 4‐CIN, also depolarized striatal neurons. Interestingly, the blockade of monocarboxylate transporters that supply lactate to neurons caused the pathological potentiation, even in the presence of enough oxygen and glucose. In this case, sevoflurane could not prevent the pathological potentiation, suggesting the involvement of monocarboxylate transporters in the sevoflurane‐mediated effects. These results indicate that sevoflurane protects striatal neurons from hypoxic damage and alleviates the pathological potentiation. Under these conditions, sevoflurane may become an effective intervention for patients undergoing surgery.
Cholinergic modulation of striatal nitric oxide‐producing interneurons
Authors: Melendez‐Zaidi Alexandria E. , Lakshminarasimhah Harini , Surmeier Dalton James
Published: July 2019

Striatal GABAergic interneurons that express nitric oxide synthase—so‐called low‐threshold spike interneurons (LTSIs)—play several key roles in the striatum. But what drives the activity of these interneurons is less well defined. To fill this gap, a combination of monosynaptic rabies virus mapping (msRVm), electrophysiological and optogenetic approaches were used in transgenic mice in which LTSIs expressed either Cre recombinase or a fluorescent reporter. The rabies virus studies revealed a striking similarity in the afferent connectomes of LTSIs and neighboring cholinergic interneurons, particularly regarding connections arising from the parafascicular nucleus of the thalamus and cingulate cortex. While optogenetic stimulation of cingulate inputs excited both cholinergic interneurons and LTSIs, thalamic stimulation excited cholinergic interneurons, but inhibited LTSIs. This inhibition was dependent on cholinergic interneurons and had two components: a previously described GABAergic element and one that was mediated by M4 muscarinic acetylcholine receptors. In addition to this phasic signal, cholinergic interneurons tonically excited LTSIs through a distinct, M1 muscarinic acetylcholine receptor pathway. This coordinated cholinergic modulation of LTSIs predisposed them to rhythmically burst in response to phasic thalamic activity, potentially reconfiguring striatal circuitry in response to salient environmental stimuli.
Under‐ice metabolism in a shallow lake in a cold and arid climate
Authors: Song Shuang , Li Changyou , Shi Xiaohong , Zhao Shengnan , Tian Weidong , Li Zhijun , Bai Yila , Cao Xiaowei , Wang Qingkai , Huotari Jussi , Tulonen Tiina , Uusheimo Sari , Leppäranta Matti , Loehr John , Arvola Lauri
Published: July 2019

Winter is a long period of the annual cycle of many lakes in the northern hemisphere. Low irradiance, ice, and snow cover cause poor light penetration into the water column of these lakes. Therefore, in northern lakes, respiration often exceeds primary production leading to low dissolved oxygen concentrations. This study aimed to quantify under‐ice metabolic processes during winter in an arid zone lake with little snow cover.

This study was carried out in a mid‐latitude lake in Inner Mongolia, northern China. The study lake receives relatively high incoming solar radiation on the ice in mid‐winter, and radiation can penetrate down to the bottom sediment as the lake is shallow and the ice lacks snow cover.

Primary production and respiration were estimated during two winters using high‐frequency sensor measurements of dissolved oxygen. To quantify under‐ice metabolic processes, sensors were deployed to different depths. During both winters, sensors collected data every 10 min over several weeks.

The amount of solar radiation controlled photosynthesis under ice; temperature and photosynthesis together appeared to control respiration. The balance between gross primary production and ecosystem respiration was especially sensitive to changes in snow cover, and the balance between P and R decreased.

Our data suggest that photosynthesis by plankton, submerged plants, and epiphytic algae may continue over winter in shallow lakes in mid‐latitudes when there is no snow cover on the ice, as may occur in arid climates. The continuation of photosynthesis under ice buffers against dissolved oxygen depletion and prevents consequent harmful ecosystem effects.
The importance of seasonal macrophyte cover for the behaviour and performance of brown trout (Salmo trutta) in a groundwater‐fed river
Authors: Vowles Andrew S. , Kemp Paul S.
Published: July 2019

Groundwater‐fed rivers, such as the chalk streams of southern England, exhibit high levels of stability (e.g. flow and temperature) and physical homogeneity (e.g. depth and substrate grain size). However, growth of instream macrophytes is highly variable depending on season, providing an important but ever‐changing source of cover for stream‐dwelling salmonids, such as brown trout (Salmo trutta).

In this study, the behavioural ecology of brown trout inhabiting a chalk stream was assessed during periods that included summer and winter. In a reach of the River Lambourn (Berkshire, UK), a combination of physical habitat mapping, electric‐fishing, passive integrated transponder and radio telemetry was used to quantify trout: (1) density relative to physical and thermal characteristics; (2) movement patterns; and (3) performance, in terms of growth.

Trout density was positively related to depth during winter (February) and spring (May), but not at the end of summer (September). Despite no statistical relation between trout density and macrophytes, periods of strong and no association between density and depth coincided with sparse and extensive macrophyte cover throughout the study reach, respectively.

Despite being greater for some fish in winter compared to summer, the daily distance moved was generally low (<3.5 m/day). While growth was mostly positive, less mass was gained, and performance deviated farther from optimal levels predicted by a growth model, during periods that included winter.

A number of factors probably contributed to lower growth in winter, including costs of reproduction, temperatures—which deviated farther from those optimal for growth—and/or an inability to maximise energy intake, e.g. due to time spent holding position in deeper areas as cover provided by macrophytes declined.

Despite the lack of extremes in chalk stream environments, the behavioural ecology of brown trout appears to be influenced by seasonal variation in instream cover provided by macrophytes. This emphasises the importance of balancing the management (e.g. cutting and removal) of macrophytes with the ecological benefits they provide.