bluuebunny/crossref_metadata_2025 huggingface dataset:
Employee engagement in CSR initiatives and customer‐directed counterproductive work behavior (CWB): The mediating roles of organizational civility norms and job calling
Authors: Hur Won‐Moo , Moon Tae‐Won , Lee Han‐Geun
Published: May 2018

This study aims to examine how service employees' perceptions of corporate social responsibility (CSR) affect their customer‐directed counterproductive work behavior (CWB) and the mediation of this link through their organizational civility norms and job calling. Working with a sample of 252 frontline employees in South Korea hotels, structural equation modeling is employed to test research hypotheses. The results of this study suggest that service employees' perceptions of CSR are negatively related to their customer‐directed CWB. Second, service employees' organizational civility norms mediated the negative relationship between service employees' perceptions of CSR and customer‐directed CWB. Third, service employees' job calling also mediated the negative relationship between their perceptions of CSR and customer‐directed CWB. Finally, the relationship between service employees' perceptions of CSR and customer‐directed CWB is sequentially and fully mediated by organizational civility norms and job calling. The theoretical and managerial implications of the results and limitations of the study are discussed, and future research directions are suggested.
Comparison between preprandial vs. postprandial insulin aspart in patients with type 1 diabetes on insulin pump and real‐time continuous glucose monitoring
Authors: Thuillier Philippe , Sonnet Emmanuel , Alavi Zarrin , Roudaut Nathalie , Nowak Emmanuel , Dion Angélina , Kerlan Véronique
Published: May 2018

Background

The objective was to compare glycemic control between preprandial and postprandial bolus administration (15 min before [PRE] or immediately after the meal [POST]) in patients with type 1 diabetes using insulin pump and real‐time continuous glucose monitoring.

Methods

Between September 2015 and February 2016, a single‐centre, open randomized, 2‐way crossover study of patients on bolus insulin aspart administration was conducted during two 14‐day periods and according to 2 administration regimen schedules (PRE/POST or POST/PRE). Inclusion criteria were as follows: patients with type 1 diabetes, ≥18 and ≤ 65 years old, treated with insulin aspart using a Medtronic® insulin pump and trained on functional insulin therapy. Patients were randomly assigned to either regimen schedule. At the beginning of each period, each patient was provided with a standardized high fat meal. Primary outcome was the area under the curve for interstitial glucose above 140 mg/dL per minute (AUC > 140 mg/dL/min) during each period. Secondary outcomes were time spent in hypo/eu/hyperglycemia, glycemic variability indices, and AUC during 4 hours after high fat meal calculated with continuous glucose monitoring data.

Results

Twenty‐two patients were included. Mean AUC > 140 mg/dL/min was statistically higher in patients on POST (43.70 mg/dL/min; 95%CI: 34.08 to 53.31) versus PRE insulin aspart regimen (37.24 mg/dL/min 95%CI: 27.63 to 46.85) (P = 0.03). Mean interstitial glycemia and glycemic variability indices were also increased (P < 0.05) on POST regimen. The mean AUC 4 hours after the high fat meal was higher on POST regimen but not statistically different (P = 0.06).

Conclusions

In our study, postprandial administration of insulin aspart appears to mildly increase glycemic excursion and glycemic variability.
Determining the effects of adulterants on drug detection via enzyme‐linked immunosorbent assay and adulterant tests strips
Authors: Olivieri Bianca , Marić Mark , Bridge Candice
Published: May 2018

The use of immunoassays for drug screening has increased due to their sensitivity towards target analytes, specifically the enzyme‐linked immunosorbent assay (ELISA) technique. Adulterant test strips are commonly used in conjunction with immunoassay tests to ensure the integrity of the specimen has not been altered prior to drug screening. This research focuses on determining which adulterants can produce a false negative result, not only with 1 of the screening tests, but throughout the entire screening process. Seven adulterants were tested for their ability to generate false negative results for the ELISA by decreasing the detectable antigen concentration to below industry‐used cut‐off levels. Each adulterant was added to a urine sample containing 1 of 5 different drugs at 5 different concentrations (0, 5, 10, 25, and 50%). Five different urine samples that contained drugs and drug metabolites of benzoylecgonine, THC‐COOH, α‐PVP, D‐amphetamine, and Diazepam, were treated with each of the 7 adulterants and analyzed on the ELISA and subsequently by 2 different test strips. The results indicated that 4 adulterants (ie, bleach, Drano®, vinegar, and sodium nitrite) generated the most false negatives for both test strips and the ELISA at surprisingly low concentrations, ~5% v/v. Thus indicating that there are still ways that a urine sample that contains drugs could be analyzed and labeled “clean and free of drugs” after going through a common screening process. These results suggest that new drug screening techniques need to be developed to detect adulterants in urine samples for drug screening.
The experiences of medical students with dyslexia: An interpretive phenomenological study
Authors: Shaw Sebastian C. K. , Anderson John L.
Published: May 2018

This article explores the experiences of U.K. medical students with dyslexia, using an interpretive phenomenological approach. This project began with a review of the literature, highlighting a void of qualitative research. We then conducted a collaborative autoethnography. This paper forms the next stage in this series of research. We aimed to elicit meaning and understanding from the lived experiences of our participants. Eight U.K. junior doctors with dyslexia were interviewed over the telephone in an in‐depth, unstructured manner. Audio recordings were transcribed verbatim and thematically analysed with the aid of a template analysis. Experiences of helplessness and hopelessness were common. These may be a result of a fear of stigmatization and personal feelings of inadequacy. They may also be fuelled by the incidents of bullying and belittling from other medical students that were reported. An important meta‐theme was of fear and lack of understanding. A lack of pastoral support was also reported. Their experiences of medical school assessments are also reported. More may need to be done to educate teachers and clinical supervisors on dyslexia.
Analyzing big data in social media: Text and network analyses of an eating disorder forum
Authors: Moessner Markus , Feldhege Johannes , Wolf Markus , Bauer Stephanie
Published: May 2018

Objective

Social media plays an important role in everyday life of young people. Numerous studies claim negative effects of social media and media in general on eating disorder risk factors. Despite the availability of big data, only few studies have exploited the possibilities so far in the field of eating disorders.

Method

Methods for data extraction, computerized content analysis, and network analysis will be introduced. Strategies and methods will be exemplified for an ad‐hoc dataset of 4,247 posts and 34,118 comments by 3,029 users of the proed forum on Reddit.

Results

Text analysis with latent Dirichlet allocation identified nine topics related to social support and eating disorder specific content. Social network analysis describes the overall communication patterns, and could identify community structures and most influential users. A linear network autocorrelation model was applied to estimate associations in language among network neighbors. The supplement contains R code for data extraction and analyses.

Discussion

This paper provides an introduction to investigating social media data, and will hopefully stimulate big data social media research in eating disorders. When applied in real‐time, the methods presented in this manuscript could contribute to improving the safety of ED‐related online communication.
Symbiotic flagellate protists as cryptic drivers of adaptation and invasiveness of the subterranean termite Reticulitermes grassei Clément
Authors: Duarte Sónia , Nobre Tânia , Borges Paulo A. V. , Nunes Lina
Published: May 2018

Changes in flagellate protist communities of subterranean termite Reticulitermes grassei across different locations were evaluated following four predictions: (i) Rural endemic (Portugal mainland) termite populations will exhibit high diversity of symbionts; (ii) invasive urban populations (Horta city, Faial island, Azores), on the contrary, will exhibit lower diversity of symbionts, showing high similarity of symbiont assemblages through environmental filtering; (iii) recent historical colonization of isolated regions—as the case of islands—will imply a loss of symbiont diversity; and (iv) island isolation will trigger a change in colony breeding structure toward a less aggressive behavior. Symbiont flagellate protist communities were morphologically identified, and species richness and relative abundances, as well as biodiversity indices, were used to compare symbiotic communities in colonies from urban and rural environments and between island invasive and mainland endemic populations. To evaluate prediction on the impact of isolation (iv), aggression tests were performed among termites comprising island invasive and mainland endemic populations. A core group of flagellates and secondary facultative symbionts was identified. Termites from rural environments showed, in the majority of observed colonies, more diverse and abundant protist communities, probably confirming prediction (i). Corroborating prediction (ii), the two least diverse communities belong to termites captured inside urban areas. The Azorean invasive termite colonies had more diverse protist communities than expected and prediction (iii) which was not verified within this study. Termites from mainland populations showed a high level of aggressiveness between neighboring colonies, in contrast to the invasive colonies from Horta city, which were not aggressive to neighbors according to prediction (iv). The symbiotic flagellate community of R. grassei showed the ability to change in a way that might be consistent with adaptation to available conditions, possibly contributing to optimization of the colonization of new habitats and spreading of its distribution area, highlighting R. grassei potential as an invasive species.
Development of an electrode for carrots using conductive unvulcanized rubber
Authors: Tada Yasunori , Inoue Masahiro
Published: May 2018

Electrical impedance of plants is related to condition of the plant's cell tissue. In existing works, the impedance has been utilized for understanding the condition of the plant. There are three kinds of electrode for measuring the impedance: a needle electrode, a metallic foil electrode, and a conductive gel electrode. However, these electrodes have problems. The needle electrode injures the plants. The metallic foil electrode does not stably contact to the plant because the plants has curve and convexo–concave surface. The conductive gel electrode including NaCl blasts the plants. We proposed a conductive unvulcanized rubber electrode for measuring the electrical impedance of the carrots. Characteristics of the conductive unvulcanized rubber electrode were soft, deformable, and self‐adhesive. Thus, the electrode was noninvasive and did not damage to the carrots. In experiments, we showed that the conductive unvulcanized rubber electrode could be utilized for measuring electrical impedance of a carrot for 912 h. Moreover, we observed that the contact area of the electrode was larger than the contact area of a conductive adhesive tape electrode.
Wave of fire: an anthropogenic signal in historical fire regimes across central Pennsylvania,USA
Authors: Stambaugh Michael C. , Marschall Joseph M. , Abadir Erin R. , Jones Benjamin C. , Brose Patrick H. , Dey Daniel C. , Guyette Richard P.
Published: May 2018

Increasingly detailed records of long‐term fire regime characteristics are needed to test ecological concepts and inform natural resource management and policymaking. We reconstructed and analyzed twelve 350+ yr‐long fire scar records developed from 2612 tree‐ring dated fire scars on 432 living and dead pine (Pinus pungens,Pinus rigida,Pinus resinosa,Pinus echinata) trees from across central Pennsylvania. We used multiple spatial and time series analysis methods to quantify fire regime characteristics (frequency, seasonality, percentages of trees scarred, extent) and fire–climate–human associations. Prior to the 20th‐century fire suppression, fire regimes at the majority of sites consisted of frequent, low‐to‐moderate severity, dormant season fires. Fires were often regionally synchronous when preceded by significantly dry years. Using documentary archives, we provide the first description of a “wave of fire”—an anthropogenic signal in fire frequency that progressively moved across the region. This “wave of fire” reflects a changing progression of anthropogenic fire regimes from Native American occupation and depopulation, to Euro‐American settlement, to industrialization and declining fire use up to the 20th century era of fire suppression. The wave of fire provides a new perspective on historical and modern fire regime dynamics and identifies socio‐ecological impacts since North American colonization. Because the anthropogenic wave of fire exists at sites across North America, we emphasize the need for a broader determination of its geographic prevalence and variability as such determinations could influence historical ecology interpretations and perspectives on past and future roles of humans in managing ecosystems with fire.
Proteomic definition of human mucosal‐associated invariant T cells determines their unique molecular effector phenotype
Authors: Bulitta Björn , Zuschratter Werner , Bernal Isabel , Bruder Dunja , Klawonn Frank , von Bergen Martin , Garritsen Henrikus Stephanus Paulus , Jänsch Lothar
Published: May 2018

Mucosal‐associated invariant T cells (MAIT) constitute the most abundant anti‐bacterial CD8+ T‐cell population in humans. MR1/TCR‐activated MAIT cells were reported to organize cytotoxic and innate‐like responses but knowledge about their molecular effector phenotype is still fragmentary. Here, we have examined the functional inventory of human MAIT cells (CD3+Vα7.2+CD161+) in comparison with those from conventional non‐MAIT CD8+ T cells (cCD8+) and NK cells. Quantitative mass spectrometry characterized 5500 proteins of primary MAIT cells and identified 160 and 135 proteins that discriminate them from cCD8+ T cells and NK cells donor‐independently. Most notably, MAIT cells showed a unique exocytosis machinery in parallel to a proinflammatory granzyme profile with high levels of the granzymes A, K, and M. Furthermore, 24 proteins were identified with highest abundances in MAIT cells, including CD26, CD98, and L‐amino‐oxidase (LAAO). Among those, expression of granzyme K and CD98 were validated as MAIT‐specific with respect to non‐MAIT CD8+ effector subsets and LAAO was found to be recruited together with granzymes, perforin, and CD107a at the immunological synapse of activated MAIT cells. In conclusion, this study complements knowledge on the molecular effector phenotype of MAIT cells and suggest novel immune regulatory functions as part of their cytotoxic responses.
Field‐Induced SMM and Visible/NIR‐Luminescence Behaviour of Dinuclear LnIII Complexes with 2‐Fluorobenzoate
Authors: Casanovas Berta , Font‐Bardía Mercè , Speed Saskia , El Fallah Mohamed Salah , Vicente Ramon
Published: May 2018

The reaction of Ln(NO3)2·6H2O salts (Ln = Nd, Eu, Gd, Tb, Dy, Er and Yb) with 2‐fluorobenzoic acid (H‐2‐FBz) and 1,10‐phenanthroline (phen) in ethanol/water mixture allows the isolation of dinuclear compounds of the formula [Ln2(2‐FBz)4(NO3)2(phen)2] {Ln = Nd (1), Eu (2), Gd (3), Tb (4), Dy (5), Er (6)} and [Yb2(2‐FBz)6(phen)2] (7). The solid‐state photoluminescence study of the complexes shows the 4f–4f lanthanide transitions in the visible range, in the cases of 2, 4 and 5, and in the NIR range for 1, 6 and 7. Magnetic studies reveal field‐induced single‐molecule‐magnet (SMM) behaviour for compounds 1, 5, 6 and 7.
Diversification of Trifluoromethylthiolation of Aromatic Molecules with Derivatives of Trifluoromethanesulfenamide
Authors: Horvat Monika , Jereb Marjan , Iskra Jernej
Published: May 2018

Trifluoromethylthiolation of aromatic compounds with different electrophilic reagents of the type ArNHSCF3 was studied in the presence of triflic acid as an activator. The effect of the reagent structure on the reactivity was studied with three different reagents: PhNHSCF3 (H/SCF3, 1a), 4‐ClC6H4NHSCF3 (Cl/SCF3, 1b) and C6F5NHSCF3 (F5/SCF3, 1c). p‐Chloro substituted reagent 1b was more stable than the unsubstituted 1a and was the most effective because it could not react by trifluoromethylthiolation of itself. This reaction was the most important side reaction of 1a. The pentafluoro derivative 1c was less reactive. Solvent played an important role in the transformation and, depending on the substrate, dichloromethane, hexane or trifluoroacetic acid gave the best yield of various trifluoromethylthiolated aromatic molecules (63–98 %).
Electrochemical Detection of Positively Charged Carbon Nanoparticles Suspension in Flow
Authors: Gocyla Mateusz , Dolinska Joanna , Rostkowska Natalia , Opallo Marcin
Published: May 2018

The electrochemical behaviour of suspended nanoparticles received some attention recently. Very few studies are performed in the flow system. Here, we have demonstrated that injection of positively charged (with ammonium functionalities) carbon nanoparticles suspension to flowing ascorbic acid solution significantly enhances its chronoamperometric response and can be used for these nanoparticles detection. This is because of electrocatalytic properties of these nanoparticles towards ascorbic acid electrooxidation. The magnitude of the signal depends on the type of flow system and is larger than in the case of suspension of negatively charged nanoparticles. It is also proportional to the concentration of nanoparticles. Their adsorption on the electrode surface plays the crucial role in the electrode process.
Current state‐of‐art of STR sequencing in forensic genetics
Authors: Alonso Antonio , Barrio Pedro Alberto , Müller Petra , Köcher Steffi , Berger Burkhard , Martin Pablo , Bodner Martin , Willuweit Sascha , Parson Walther , Roewer Lutz , Budowle Bruce
Published: May 2018

The current state of validation and implementation strategies of massively parallel sequencing (MPS) technology for the analysis of STR markers for forensic genetics use is described, covering the topics of the current catalog of commercial MPS‐STR panels, leading MPS‐platforms, and MPS‐STR data analysis tools. In addition, the developmental and internal validation studies carried out to date to evaluate reliability, sensitivity, mixture analysis, concordance, and the ability to analyze challenged samples are summarized. The results of various MPS‐STR population studies that showed a large number of new STR sequence variants that increase the power of discrimination in several forensically relevant loci are also presented. Finally, various initiatives developed by several international projects and standardization (or guidelines) groups to facilitate application of MPS technology for STR marker analyses are discussed in regard to promoting a standard STR sequence nomenclature, performing population studies to detect sequence variants, and developing a universal system to translate sequence variants into a simple STR nomenclature (numbers and letters) compatible with national STR databases.
Complementary middle‐down and intact monoclonal antibody proteoform characterization by capillary zone electrophoresis – mass spectrometry
Authors: Belov Arseniy M. , Zang Li , Sebastiano Roberto , Santos Marcia R. , Bush David R. , Karger Barry L. , Ivanov Alexander R.
Published: May 2018

High‐resolution capillary zone electrophoresis – mass spectrometry (CZE‐MS) has been of increasing interest for the analysis of biopharmaceuticals. In this work, a combination of middle‐down and intact CZE‐MS analyses has been implemented for the characterization of a biotherapeutic monoclonal antibody (mAb) with a variety of post‐translational modifications (PTMs) and glycosylation structures. Middle‐down and intact CZE separations were performed in an acidified methanol‐water background electrolyte on a capillary with a positively charged coating (M7C4I) coupled to an Orbitrap mass spectrometer using a commercial sheathless interface (CESI). Middle‐down analysis of the IdeS‐digested mAb provided characterization of PTMs of digestion fragments. High resolution CZE enabled separation of charge variants corresponding to 2X‐deamidated, 1X‐deamidated, and non‐deamidated forms at baseline resolution. In the course of the middle‐down CZE‐MS analysis, separation of glycoforms of the FC/2 fragment was accomplished due to hydrodynamic volume differences. Several identified PTMs were confirmed by CZE‐MS2. Incorporation of TCEP‐HCl reducing agent in the sample solvent resulted in successful analysis of reduced forms without the need for alkylation. CZE‐MS studies on the intact mAb under denaturing conditions enabled baseline separation of the 2X‐glycosylated, 1X‐glycosylated, and aglycosylated populations as a result of hydrodynamic volume differences. The presence of a trace quantity of dissociated light chain was also detected in the intact protein analysis. Characterization of the mAb under native conditions verified identifications achieved via intact analysis and allowed for quantitative confirmation of proteoforms. Analysis of mAbs using CZE‐MS represents a complementary approach to the more conventional liquid‐chromatography – mass spectrometry‐based approaches.
Evaluation of massively parallel sequencing for forensic DNA methylation profiling
Authors: Richards Rebecca , Patel Jayshree , Stevenson Kate , Harbison SallyAnn
Published: May 2018

Epigenetics is an emerging area of interest in forensic science. DNA methylation, a type of epigenetic modification, can be applied to chronological age estimation, identical twin differentiation and body fluid identification. However, there is not yet an agreed, established methodology for targeted detection and analysis of DNA methylation markers in forensic research. Recently, a massively parallel sequencing‐based approach has been suggested. The use of massively parallel sequencing is well established in clinical epigenetics and is emerging as a new technology in the forensic field. This review investigates the potential benefits, limitations, and considerations of this technique for the analysis of DNA methylation in a forensic context. The importance of a robust protocol, regardless of the methodology used, which minimizes potential sources of bias is highlighted.
Aeolian dynamics of transgressive dunefields on the southern Mozambique coast, Africa
Authors: Miguel Lucas Lavo António Jimo , Castro João Wagner Alencar
Published: May 2018

A relatively unknown coastal zone of southern Mozambique in Africa is covered by vast mobile and stabilized dunefields. The aeolian dynamics of these transgressive dunefields are studied based on mobility and stability models, statistical analysis of climate data and topographic profiles. Detailed analyses of regional winds, rainfall records, atmospheric temperature records and annual monitoring of dune migration rates helped to find reliable data about instantaneous aeolian sand transport rates, wind drift potential, dune mobility and dune migration rates. The data obtained suggest that the coastal transgressive dunefields are controlled by the southeast winds, availability of loose sediments on the beach, the presence of headland boundary between Maputo and Gaza provinces and the appropriate deposition spaces between the coastline and lacustrine‐lagoon systems. Two distinctive segments of transgressive dunefields were identified in the region studied, including the northern segment of Maputo province with active (mobile) and semi‐vegetated dunes that migrate 23 m/yr landward, and Gaza province dunefields with stabilized (vegetated) and semi‐vegetated dunes. The data obtained in this research have considerable potential to make a valuable contribution to the study of coastal dunefields. Copyright © 2018 John Wiley & Sons, Ltd.
Strong hybrid male incompatibilities impede the spread of a selfish chromosome between populations of a fly
Authors: Verspoor Rudi L. , Smith Jack M. L. , Mannion Natasha L. M. , Hurst Gregory D. D. , Price Tom A. R.
Published: May 2018

Meiotically driving sex chromosomes manipulate gametogenesis to increase their transmission at a cost to the rest of the genome. The intragenomic conflicts they produce have major impacts on the ecology and evolution of their host species. However, their ecological dynamics remain poorly understood. Simple population genetic models predict meiotic drivers will rapidly reach fixation in populations and spread across landscapes. In contrast, natural populations commonly show spatial variation in the frequency of drivers, with drive present in clines or mosaics across species ranges. For example, Drosophila subobscura harbors a sex ratio distorting drive chromosome (SRs) at 15–25% frequency in North Africa, present at less than 2% frequency in adjacent southern Spain, and absent in other European populations. Here, we investigate the forces preventing the spread of the driver northward. We show that SRs has remained at a constant frequency in North Africa, and failed to spread in Spain. We find strong evidence that spread is impeded by genetic incompatibility between SRs and Spanish autosomal backgrounds. When we cross SRs from North Africa onto Spanish genetic backgrounds we observe strong incompatibilities specific to hybrids bearing SRs. The incompatibilities increase in severity in F2 male hybrids, leading to almost complete infertility. We find no evidence supporting an alternative hypothesis, that there is resistance to drive in Spanish populations. We conclude that the source of the stepped frequency variation is genetic incompatibility between the SRs chromosome and the genetic backgrounds of the adjacent population, preventing SRs spreading northward. The low frequency of SRs in South Spain is consistent with recurrent gene flow across the Strait of Gibraltar combined with selection against the SRs element through genetic incompatibility. This demonstrates that incompatibilities between drive chromosomes and naïve populations can prevent the spread of drive between populations, at a continental scale.
Chronology, petrology, geochemistry and tectonic environment of the Bailingshan complex in Eastern Tianshan, Xinjiang, NW China
Authors: Fan Shuanghu , Chen Shu'e , Liu Lei , Zhang Yibin , Zhang Li , Zhang Tianyu , Yang Liu‐Chen
Published: May 2018

The Bailingshan complex distributed in the Jueluotage tectonic belt of Eastern Tianshan is composed of quartz monzodiorite, granodiorite, monzogranite, and granite. The petrography and petrochemistry of the complex have the features of metaluminous–high K calc‐alkaline series. The ages obtained by zircon U–Pb dating from different rocks indicate that quartz monzodiorite, granodiorite, monzogranite, and granite formed in 314.2 ± 3.5, 302.5 ± 3.8, 298.2 ± 3.6, and 310.9 ± 4.7 Ma, respectively, which is equivalent to the Late Carboniferous–Early Permian. The unconformity between the Lower Carboniferous and Upper Carboniferous in the Jueluotage tectonic belt indicates that the collisional orogen finished in the later period of the Early Carboniferous in this area, and that it began to enter the post‐collisional extension from the Late Carboniferous. The magmatic intrusion is a sign of the extensional activity of the Jueluotage tectonic belt in the Late Carboniferous–Early Permian.
Nucleus reuniens of the thalamus controls fear memory intensity, specificity and long‐term maintenance during consolidation
Authors: Troyner Fernanda , Bicca Maíra A. , Bertoglio Leandro J.
Published: May 2018

The thalamic nucleus reuniens (NR) has been shown to support bidirectional medial prefrontal cortex‐hippocampus communication and synchronization relevant for cognitive processing. Using non‐selective or prolonged inactivation of the NR, previous studies reported its activity positively modulates aversive memory consolidation. Here we examined the NR's role in consolidating contextual fear memories with varied strength, at both recent and more remote time points, using muscimol‐induced temporary inactivation in rats. Results indicate the NR negatively modulates fear memory intensity, specificity, and long‐term maintenance. The more intense, generalized, and enduring fear memory induced by NR inactivation during consolidation was less prone to behavioral suppression by extinction or reconsolidation disruption induced by clonidine, an alpha‐2 adrenergic receptor agonist. Lastly, we used immunohistochemistry for Arc protein, which is involved in synaptic modifications underlying memory consolidation, to investigate whether treatment condition and/or conditioning status could change its levels not only in the NR, but also in the hippocampus (dorsal and ventral CA1 subregions) and the medial prefrontal cortex (anterior cingulate, prelimbic and infralimbic subregions). Results indicate a significant imbalance in the number of Arc‐expressing neurons in the brain areas investigated in muscimol fear conditioned animals when compared with controls. Collectively, present results provide convergent evidence for the NR's role as a hub regulating quantitative and qualitative aspects of a contextual fear memory during its consolidation that seem to influence the subsequent susceptibility to experimental interventions aiming at attenuating its expression. They also indicate the selectivity and duration of a given inactivation approach may influence its outcomes.
Photobiomodulation induces antinociception, recovers structural aspects and regulates mitochondrial homeostasis in peripheral nerve of diabetic mice
Authors: da Silva Oliveira Victória R. , Cury Diego P. , Yamashita Laura B. , Esteca Marcos V. , Watanabe Ii‐Sei , Bergmann Yoko Fee , Toniolo Elaine F. , Dale Camila S.
Published: May 2018

Diabetic peripheral neuropathy (DPN) is a nervous disorder caused by diabetes mellitus, affecting about 50% of patients in clinical medicine. Chronic pain is one of the major and most unpleasant symptoms developed by those patients, and conventional available treatments for the neuropathy, including the associated pain, are still unsatisfactory and benefit only a small number of patients. Photobiomodulation (PBM) has been gaining clinical acceptance once it is able to promote early nerve regeneration resulting in significant improvement in peripheral nerves disabilities. In this work, the effects of PBM (660 nm, 30 mW, 1.6 J/cm2, 0.28 cm2, 15 s in a continuous frequency) on treating DPN‐induced pain and nerve damage were evaluated in an experimental model of diabetic‐neuropathy induced by streptozotocin in mice. PBM‐induced antinociception in neuropathic‐pain mice was dependent on central opioids release. After 21 consecutive applications, PBM increased nerve growth factor levels and induced structural recovery increasing mitochondrial content and regulating Parkin in the sciatic nerve of DPN‐mice. Taking together, these data provide new insights into the mechanisms involved in the effects of PBM‐therapy emphasizing its therapeutic potential in the treatment of DPN.
Association Between Body Mass Index and the Risk of Hip Fracture by Sex and Age: A Prospective Cohort Study
Authors: Kim Se Hwa , Yi Sang-Wook , Yi Jee-Jeon , Kim Yoo Mee , Won Young Jun
Published: May 2018

The association between body mass index (BMI) and hip fracture may differ by ethnic group. We examined the association between BMI and hip fracture according to sex and age and to identify BMI ranges associated with the lowest risk in Korean men and women. We followed up 288,068 Korean adults (aged 50 to 80 years), who underwent health examinations in 2002–03 to 2013; we examined national hospital discharge records. Hazard ratios (HRs) were calculated using Cox proportional hazard models after adjusting for confounders. During a mean follow-up period of 10.5 years, 1502 men and 2432 women suffered a hip fracture. Nonlinear associations were observed between BMI and hip fracture: a U-curve for women and a reverse J-curve for men. Men with BMIs of 27.5 to 29.9 kg/m2 and women with BMIs of 25 to 27.4 kg/m2 showed the lowest incidence of hip fracture. The multivariate-adjusted HRs for hip fracture per 5 kg/m2 decrease in BMI were 2.09 (95% confidence interval [CI] 1.83–2.38) and 1.34 (95% CI 1.19–1.51) in men and women with BMI <25 kg/m2. The HRs were generally highest in the age group of 50 to 59 years (HR = 3.42 in men and 2.27 in women) and thereafter decreased with age. Among participants with BMI ≥25 kg/m2, the HRs for hip fracture per 5 kg/m2 increase in BMI were 1.26 (95% CI 1.08–1.47) in women and 0.91 (95% CI 0.62–1.33) in men. In conclusion, the overweight range of BMI was associated with the lowest risk of hip fracture. Lower BMI was a risk factor for hip fracture, whereas obesity was associated with an increased risk of hip fracture, particularly in women. Overweight may be protective against hip fracture in Asian adults but not obesity. © 2018 American Society for Bone and Mineral Research.
LRP1 Suppresses Bone Resorption in Mice by Inhibiting the RANKL-Stimulated NF-κB and p38 Pathways During Osteoclastogenesis
Authors: Lu Di , Li Jianshuang , Liu Huadie , Foxa Gabrielle E , Weaver Kevin , Li Jie , Williams Bart O , Yang Tao
Published: May 2018

Single-nucleotide polymorphisms in the LRP1 gene coding sequence are associated with low bone mass, and cell culture studies suggest that LRP1 plays a role in osteoblast proliferation and osteoblast-mediated osteoclastogenesis. However, the in vivo function of LRP1 in bone homeostasis has not been explored. In this work, we studied the osteoclast-specific role of LRP1 in bone homeostasis using a Ctsk-Cre;Lrp1f/f mouse model on the C57BL/6J background. These mice had a dramatically decreased trabecular bone mass with markedly more osteoclasts, while the osteoblast activity was unaffected or slightly increased. The cortical bone parameters were largely unaltered. Upon RANKL treatment, Lrp1-deficient bone marrow monocytes more efficiently differentiated into osteoclasts and showed elevated p65 NFκB and p38 signaling. Consistently, Lrp1-overexpressing Raw264.7 cells were desensitized to RANKL-induced p38 and p65 activation and osteoclastogenesis. Moreover, RANKL treatment led to a sharp decrease of LRP1 protein and RNA in BMMs. Overall, our data suggest that osteoclast-expressed LRP1 is a crucial regulator of bone mass. It inhibits the NFκB and p38 pathways and lessens the efficiency of RANKL-induced osteoclastogenesis. © 2018 American Society for Bone and Mineral Research.
Roles of methyltrienolone (R1881) in AKTs and AR expression patterns of cultured granulosa‐lutein cells
Authors: Nekoonam Saeid , Naji Mohammad , Mortezaee Keywan , Amidi Fardin
Published: May 2018

AR‐mediated androgen signaling plays a key role in female reproductive system. Granulosa‐lutein cells (GCs) are the main sites for expression of androgen receptor (AR). There is also a close relation between AKT signaling and AR. Here, we assayed the role for a synthetic AR ligand methyltrienolone (R1881) in expressions of AKTs and AR. Controlled ovarian hyperstimulation (COH) was performed in 20 normal women. Mural GCs were isolated by filtration method, cultured, and passaged. Then, the cells were starved for 48 h with 10% charcoal stripped FBS. The cells were then treated with R1881, bicalutamide (AR blocker), LY294002 (PI3K/AKT pathway blocker), and combination of them for 48 h. Finally, GCs were evaluated for quantitative real‐time PCR analysis of AKT1, AKT2, AKT3, and AR, and also Western blot assessment of total AKT and phosphorylated AKT (p‐AKT) [Ser473 and Thr308]. Addition of R1881 to the GCs culture showed high expressions of AKT1, AKT2, and AKT3 (P ≤ 0.05 vs LY294002 group and bicalutamide group). Expressions of AKT1 and AKT2 were decreased in the GCs under exposure to bicalutamide or LY294002 (P ≤ 0.05 vs R1881). AKT1, AKT2, and AKT3 showed decreased rates of expressions in the LY294002 + bicalutamide group (P ≤ 0.05 vs R1881). AR, total AKT and p‐AKT showed no significant differences between groups. Our findings indicate that 46 h exposure with R1881 could affect AKTs expressions in the GCs of pre‐ovulatory phase, but it cannot promote AR expression and AKTs activation.
In silico analysis of single‐cell RNA sequencing data from 3 and 7 days old mouse spermatogonial stem cells to identify their differentially expressed genes and transcriptional regulators
Authors: Sisakhtnezhad Sajjad
Published: May 2018

Spermatogonial stem cells (SSCs), which are at the basis of spermatogenesis process, are valuable cells with different applications in biotechnology and regenerative medicine. Understanding the molecular basis of SSC self‐renewal and differentiation at various developmental stages of the male organism is crucial to find key factors in the SSCs fate and function. Therefore, this study was aimed to use single‐cell RNA‐sequencing dataset analysis for identification of differentially expressed genes (DEGs) and their regulators in 3 and 7 days old mouse‐derived single SSCs (mSSCs). Results showed 68 upregulated and 203 downregulated genes in 7 days old mouse‐derived SSCs compared to 3 days old mSSCs, which were associated with 1493 and 3077 biological processes, respectively. It also found that DAZL, FKBP6, PAIP2, DDX4, H3F3B, TEX15, XRN2, MAEL, and SOD1 are important factors with the higher gene expression pattern, which may be pivotal for mSSCs fate and function during development of germ cells. Moreover, NR3C1, RXRA, NCOA, ESR1, PML, ATF2, BMI1, POU5F1, and CHD1 were the main central regulators for the upregulated DEGs, while HNF1A, C/EBPα, and NFATC1 were the master regulators for the downregulated DEGs. In this regard, two significant protein complexes were found in the protein‐protein interactions network for the upregulated DEGs regulators. Furthermore, 24 protein kinases detected upstream of the main central regulators of DEGs. In conclusion, this study presents DEGs and their transcriptional regulators that are crucial for inducing and regulating SSCs commitment during development, and for developing efficient protocols to identify and isolate SSCs for different applications.
Circulating lncRNA IFNG‐AS1 expression correlates with increased disease risk, higher disease severity and elevated inflammation in patients with coronary artery disease
Authors: Xu Yahuan , Shao Bibo
Published: May 2018

Background

This study aimed to investigate the associations of circulating long, non‐coding (lncRNA) IFNG‐AS1, lncRNA ANRIL and lncRNA ITSN1 relative expressions with disease risk, severity and inflammatory cytokines levels in coronary artery disease (CAD) patients.

Methods

One hundred and ninety‐one patients suspected of CAD who underwent coronary angiography were consecutively enrolled in this casecontrol study, and divided into CAD patients (N = 102) and controls (N = 89) according to coronary angiographic results. Blood samples of all participants were collected. Plasma lncRNA IFNG‐AS1, lncRNA ANRIL and lncRNA ITSN1 expressions were detected using quantitative polymerase chain reaction (qPCR). Serum tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β (IL‐1β), IL‐6, IL‐8, IL‐10, and IL‐17 were assessed using enzyme‐linked immunosorbent assay (ELISA). Gensini Score was used to evaluate the disease severity of CAD patients.

Results

LncRNA IFNG‐AS1 relative expression in CAD patients was upregulated compared with that in controls (P < .001), and the receiver operating characteristic (ROC) curve showed that the area under curve (AUC) of lncRNA‐IFNG‐AS1 for predicting the risk of CAD was 0.755 (95% CI: 0.688‐0.821). lncRNA IFNG‐AS1 relative expression was remarkably associated with Gensini Score (r = .259, P = .009). Additionally, lncRNA IFNG‐AS1 relative expression was positively associated with high‐sensitivity C‐reactive protein (hs‐CRP) (r = .283, P = .004), TNF‐α (r = .269, P = .006), and IL‐6 levels (r = .425, P < .001), while it was negatively correlated with IL‐10 level (r = −.263, P = .008). lncRNA ANRIL or lncRNA ITSN1 was not correlated with CA D risk, Gensini Score, hs‐CRP, ESR, TNF‐α, IL‐1β, IL‐6, IL‐8, IL‐10, or IL‐17 levels (all P > .05).

Conclusion

Circulating lncRNA IFNG‐AS1 expression correlates with increased disease risk, higher disease severity and elevated inflammation in CAD patients.
Synthesis of Camalexin and Related Analogues
Authors: Stremski Yordan , Statkova‐Abeghe Stela , Angelov Plamen , Ivanov Iliyan
Published: May 2018

Camalexin is synthesized on a gram scale by coupling of thiazole and indole in an amidoalkylation–oxidation sequence. Several high‐yielding implementations of this two‐step approach are demonstrated with variation of either the intermediate acyliminium reagent or the oxidation conditions. Benzo‐analogues and aza‐analogues of the natural product are also obtained by this method. As a side result, a new formylation of indole is demonstrated.
Using SMS Technology to Survey Low‐Income Youth: Lessons from a Vocational Education Tracking Study in Kenya
Authors: Lau Charles , Gachugu Ehud , Johnson Eric , Marks Leenisha
Published: May 2018

Tracking graduates of job training programs is increasingly important, given high youth unemployment and the need to understand labour market outcomes to inform policy and program decisions. We describe the strengths and weaknesses of using text messaging to survey 2180 graduates of Vocational Training Centres in three Kenyan counties. The response rate was 18 percent. The short message service survey over‐represented urban graduates and those from private Vocational Training Centres, and 39 percent were answered by someone other than the intended respondent—seriously jeopardizing data quality. We report lessons learned and offer recommendations for designing graduate tracking surveys. Copyright © 2018 John Wiley & Sons, Ltd.
IRAK4 activity controls immune responses to intracellular bacteria Listeria monocytogenes and Mycobacterium smegmatis
Authors: Pattabiraman Goutham , Murphy Michael , Agliano Federica , Karlinsey Keaton , Medvedev Andrei E
Published: May 2018

IL-1 receptor-associated kinase (IRAK) 4 is a central enzyme of the TLR pathways. This study tested the hypothesis that IRAK4 kinase activity is prerequisite for regulating innate immunity during infections with intracellular bacteria. To this end, we analyzed responses of macrophages obtained from mice expressing wild-type (WT) IRAK4 or its kinase-inactive K213M mutant (IRAK4KI) upon infection with intracellular bacteria Listeria monocytogenes or Mycobacterium smegmatis. In contrast to robust induction of cytokines by macrophages expressing kinase-sufficient IRAK4, IRAK4KI macrophages expressed decreased TNF-α, IL-6, IL-1β, and C-C motif chemokine ligand 5 upon infection with L. monocytogenes or M. smegmatis. Bacterial infection of IRAK4KI macrophages led to attenuated activation of IRAK1, MAPKs and NF-κB, impaired induction of inducible NO synthase mRNA and secretion of NO, but resulted in elevated microbial burdens. Compared with WT animals, systemic infection of IRAK4KI mice with M. smegmatis or L. monocytogenes resulted in decreased levels of serum IL-6 and CXCL-1 but increased bacterial burdens in the spleen and liver. Thus, a loss of IRAK4 kinase activity underlies deficient cytokine and microbicidal responses during infection with intracellular bacteria L. monocytogenes or M. smegmatis via impaired activation of IRAK1, MAPKs, and NF-κB but increases bacterial burdens, correlating with decreased induction of NO.

IRAK4 activity regulates induction of IRAK1, MAPKs, and NF-κB, and shapes cytokines and antimicrobial responses during infection with intracellular bacteria L. monocytogenes or M. smegmatis
Quantitative susceptibility map analysis in preterm neonates with germinal matrix‐intraventricular hemorrhage
Authors: Tortora Domenico , Severino Mariasavina , Sedlacik Jan , Toselli Benedetta , Malova Mariya , Parodi Alessandro , Morana Giovanni , Fato Marco Massimo , Ramenghi Luca Antonio , Rossi Andrea
Published: May 2018

Background

Germinal matrix‐intraventricular hemorrhage (GMH‐IVH) is a common form of intracranial hemorrhage occurring in preterm neonates that may affect normal brain development. Although the primary lesion is easily identified on MRI by the presence of blood products, its exact extent may not be recognizable with conventional sequences. Quantitative susceptibility mapping (QSM) quantify the spatial distribution of magnetic susceptibility within biological tissues, including blood degradation products.

Purpose/Hypothesis

To evaluate magnetic susceptibility of normal‐appearing white (WM) and gray matter regions in preterm neonates with and without GMH‐IVH.

Study Type

Retrospective case‐control.

Population

A total of 127 preterm neonates studied at term equivalent age: 20 had mild GMH‐IVH (average gestational age 28.7 ± 2.1 weeks), 15 had severe GMH‐IVH (average gestational age 29.3 ± 1.8 weeks), and 92 had normal brain MRI (average gestational age 29.8 ± 1.8 weeks).

Field Strength/Sequence

QSM at 1.5 Tesla.

Assessment

QSM analysis was performed for each brain hemisphere with a region of interest‐based approach including five WM regions (centrum semiovale, frontal, parietal, temporal, and cerebellum), and a subcortical gray matter region (basal ganglia/thalami).

Statistical Tests

Changes in magnetic susceptibility were explored using a one‐way analysis of covariance, according to GMH‐IVH severity (P < 0.05).

Results

In preterm neonates with normal brain MRI, all white and subcortical gray matter regions had negative magnetic susceptibility values (diamagnetic). Neonates with severe GMH‐IVH showed higher positive magnetic susceptibility values (i.e. paramagnetic) in the centrum semiovale (0.0019 versus ‐0.0014 ppm; P < 0.001), temporal WM (0.0011 versus ‐0.0012 ppm; P = 0.037), and parietal WM (0.0005 versus ‐0.0001 ppm; P = 0.002) compared with controls. No differences in magnetic susceptibility were observed between neonates with mild GMH‐IVH and controls (P = 0.236).

Data Conclusion

Paramagnetic susceptibility changes occur in several normal‐appearing WM regions of neonates with severe GMH‐IVH, likely related to the accumulation of hemosiderin/ferritin iron secondary to diffusion of extracellular hemoglobin from the ventricle into the periventricular WM.

Level of Evidence: 4

Technical Efficacy: Stage 3

J. Magn. Reson. Imaging 2018;47:1199–1207.