bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence of new 2D material: Cu2Te
Authors: Tong Yongfeng , Bouaziz Meryem , Zhang Wei , Obeid Baydaa , Loncle Antoine , Oughaddou Hamid , Enriquez Hanna , Chaouchi Karine , Esaulov Vladimir , Chen Zhesheng , Xiong Heqi , Cheng Yingchun , Bendounan Azzedine
Published: April 2020

The number of two-dimensional (2D) materials has grown steadily since the discovery of graphene. Each new 2D material demonstrated unusual physical properties offering a large flexibility in their tailoring for high-tech applications. Here, we report on the formation and characterization of an uncharted 2D material: ‘Cu2Te alloy monolayer on Cu(111) surface’. We have successfully grown a 2D binary Te-Cu alloy using a straightforward approach based on chemical deposition method. Low electron energy diffraction (LEED) and scanning tunneling microscopy (STM) results reveal the existence of a well-ordered alloy monolayer characterized by (√3 × √3)R30° superstructure, while the x-ray photoemission spectroscopy (XPS) measurements indicate the presence of single chemical environment of the Te atoms associated with the Te-Cu bonding. Analysis of the valence band properties by angle resolved photoemission spectroscopy (ARPES); in particular the electronic states close to the Fermi level suggests a strong hybridization between Te and Cu electronic states leading to an appearance of new dispersive bands localized at the surface alloy, which is confirmed by first-principles calculations. These bands are strongly influenced by the surface reconstruction and undergo a back-folding at the boundaries of the reduced surface Brillouin zone (SBZ). More interesting, a band gap of about 0.91 eV and a Rashba splitting in the conduction band are obtained. These findings taken together clearly prove the presence of 2D-type electron system within the Cu2Te alloy layer, which is promising for spintronic application.
Electrical percolation and dynamic piezoresistivity of silver nanoparticle/polydimethylsiloxane films
Authors: Heng Shan , Liu Hongguang , Wang Chengyuan , Tang Chun , Luo Ying , Wang Xuesen
Published: April 2020

Electrical percolation and piezo-resistivity under cyclic load were studied for silver nanoparticle (AgNP)/polydimethylsiloxane (PDMS) films. Attention was focused on the percolation process and the impacts of the percolation stage and load frequency on the piezoresistivity of the films. A power law was uncovered between the electrical resistance and the surface mass density (m

d
) of AgNP layer. Dependence of piezoresistive sensitivity and linearity on m

d
and cyclic load frequency were also investigated and interpreted in terms of the physical changes of the AgNP layer and the dynamics of the strain-induced microcracks. In particular, a peak gauge factor 75 was achieved at m

d
= 0.32 mg cm
−2 and the load frequency 0.5 Hz, and excellent linearity was found at the frequency 1 Hz or higher. These new findings provide important guidance for the design and applications of AgNP/PDMS films in body motion tracking, fatigue load monitoring and surface vibration detecting.
The love life of a rose. A commentary on: ‘Asymmetrical canina meiosis is accompanied by the expansion of a pericentric satellite in non-recombining univalent chromosomes’
Authors: Wilkinson Mike J
Published: April 2020

This article comments on:

Jana Lunerová, Veit Herklotz, Melanie Laudien, Radka Vozárová, Marco Groth, Aleš Kovařík and Christiane M. Ritz, Asymmetrical canina meiosis is accompanied by the expansion of a pericentromeric satellite in non-recombining univalent chromosomes in the genus Rosa, Annals of Botany, Volume 125, Issue 7, 4 June 2020, Pages 1025–1038, https://doi.org/10.1093/aob/mcaa028
Turgor-driven plant growth applied in a soybean functional–structural plant model
Authors: Coussement Jonas R , De Swaef Tom , Lootens Peter , Steppe Kathy
Published: April 2020

Background and Aims

Turgor pressure within a plant cell represents the key to the mechanistical descriptiion of plant growth, combining the effects of both water and carbon availability. The high level of spatio-temporal variation and diurnal dynamics in turgor pressure within a single plant make it a challenge to model these on the fine spatial scale required for functional–structural plant models (FSPMs). A conceptual model for turgor-driven growth in FSPMs has been established previously, but its practical use has not yet been explored.

Methods

A turgor-driven growth model was incorporated in a newly established FSPM for soybean. The FSPM simulates dynamics in photosynthesis, transpiration and turgor pressure in direct relation to plant growth. Comparisons of simulations with field data were used to evaluate the potential and shortcomings of the modelling approach.

Key Results

Model simulations revealed the need to include an initial seed carbon contribution, a more realistic sink function, an estimation of respiration, and the distinction between osmotic and structural sugars, in order to achieve a realistic model of plant growth. However, differences between simulations and observations remained in individual organ growth patterns and under different environmental conditions. This exposed the need to further investigate the assumptions of developmental and environmental (in)sensitivity of the parameters, which represent physiological and biophysical organ properties in the model, in future research.

Conclusions

The model in its current form is primarily a diagnostic tool, to better understand and model the behaviour of water relations on the scale of individual plant organs throughout the plant life cycle. Potential future applications include its use as a phenotyping tool to capture differences in plant performance between genotypes and growing environments in terms of specific plant characteristics. Additionally, focused experiments can be used to further improve the model mechanisms to lead to better predictive FSPMs, including scenarios of water deficit.
The Language of Evaluation in the Narratives by the Magdalene Laundries Survivors: The Discourse of Female Victimhood
Authors: HIDALGO-TENORIO ENCARNACIÓN , BENÍTEZ-CASTRO MIGUEL-ÁNGEL
Published: April 2020

Drawing on Martin and White’s Appraisal Theory, we study the language of evaluation in a corpus of interviews selected from the archives of The Magdalene Oral History Project. Apart from being deprived of proper food, clothing, and their identity, many of the women who spent their lives in Ireland’s Magdalene institutions had been, or were, sexually assaulted, and physically and psychologically abused. Their criminalization led them to long-lasting incarceration for no apparent reason and, years further on, prevented them from developing any active social voice. Thus, the discursive patterns in these texts can be seen as the symptom of ‘the discourse of female victimhood’, which is mainly characterized by their difficulty to express their emotions and their opinions, and their tendency to avoid mentioning what happened to them and who the agent was. The Magdalene survivors felt both hatred and remorse, and seemed to be able to speak about their painful experience only by silencing others’ liability, while making self-reproach and sympathy go hand in hand in their construal of both their past and themselves.
Contrasts in kinship structure in mammalian societies
Authors: Dyble Mark , Clutton-Brock Tim H
Published: April 2020

Comparative studies of mammals confirm Hamilton’s prediction that differences in cooperative and competitive behavior across species will be related to contrasts in kinship between group members. Although theoretical models have explored the factors affecting kinship within social groups, few have analyzed the causes of contrasts in kinship among related species. Here, we describe interspecific differences in average kinship between group members among social mammals and show that a simple mathematical model that includes the number of breeding females, male reproductive skew, and litter size successfully predicts ~95% of observed variation in average kinship between group members across a sample of mammals. Our model shows that a wide range of conditions can generate groups with low average relatedness but only a small and rather specific set of conditions are likely to generate high average levels of relatedness between their members, providing insight into the relative rarity of advanced forms of cooperation in mammalian societies.
MIAMI––a tool for non-targeted detection of metabolic flux changes for mode of action identification
Authors: Dudek Christian-Alexander , Reuse Carsten , Fuchs Regine , Hendriks Janneke , Starck Veronique , Hiller Karsten
Published: April 2020

Mass isotopolome analysis for mode of action identification (MIAMI) combines the strengths of targeted and non-targeted approaches to detect metabolic flux changes in gas chromatography/mass spectrometry datasets. Based on stable isotope labeling experiments, MIAMI determines a mass isotopomer distribution-based (MID) similarity network and incorporates the data into metabolic reference networks. By identifying MID variations of all labeled compounds between different conditions, targets of metabolic changes can be detected.

Availability and implementation

We implemented the data processing in C++17 with Qt5 back-end using MetaboliteDetector and NTFD libraries. The data visualization is implemented as web application. Executable binaries and visualization are freely available for Linux operating systems, the source code is licensed under General Public License version 3.
Altered cerebrovascular response to acute exercise in patients with Huntington’s disease
Authors: Steventon Jessica J , Furby Hannah , Ralph James , O’Callaghan Peter , Rosser Anne E , Wise Richard G , Busse Monica , Murphy Kevin
Published: April 2020

The objective of this study was to determine whether a single session of exercise was sufficient to induce cerebral adaptations in individuals with Huntington’s disease and to explore the time dynamics of any acute cerebrovascular response. In this case–control study, we employed arterial-spin labelling MRI in 19 Huntington’s disease gene-positive participants (32–65 years, 13 males) and 19 controls (29–63 years, 10 males) matched for age, gender, body mass index and self-reported activity levels, to measure global and regional perfusion in response to 20 min of moderate-intensity cycling. Cerebral perfusion was measured at baseline and 15, 40 and 60 min after exercise cessation. Relative to baseline, we found that cerebral perfusion increased in patients with Huntington’s disease yet was unchanged in control participants in the precentral gyrus (P = 0.016), middle frontal gyrus (P = 0.046) and hippocampus (P = 0.048) 40 min after exercise cessation (+15 to +32.5% change in Huntington’s disease participants, −7.7 to 0.8% change in controls). The length of the disease-causing trinucleotide repeat expansion in the huntingtin gene predicted the change in the precentral gyrus (P = 0.03) and the intensity of the exercise intervention predicted hippocampal perfusion change in Huntington’s disease participants (P < 0.001). In both groups, exercise increased hippocampal blood flow 60 min after exercise cessation (P = 0.039). These findings demonstrate the utility of acute exercise as a clinically sensitive experimental paradigm to modulate the cerebrovasculature. Twenty minutes of aerobic exercise induced transient cerebrovascular adaptations in the hippocampus and cortex selectively in Huntington’s disease participants and likely represents latent neuropathology not evident at rest.
Three-dimensional imaging of pulmonary arterial vasa vasorum using optical coherence tomography in patients after bidirectional Glenn and Fontan procedures
Authors: Hayabuchi Yasunobu , Homma Yukako , Kagami Shoji
Published: April 2020

Aims

We evaluated pulmonary arterial (PA) vasa vasorum (VV) in Fontan candidate patients with a novel three-dimensional (3D) imaging technique using optical coherence tomography (OCT).

Methods and results

This prospective study assessed the development of adventitial VV in the distal PA of 10 patients with bidirectional Glenn circulation (BDG group, 1.6 ± 0.3 years) and Fontan circulation (Fontan group, 3.3 ± 0.3 years), and in 20 children with normal PA haemodynamics and morphology (Control group, 1.5 ± 0.3 years). We assessed the PA VV with two-dimensional (2D) cross-sectional, multi-planar reconstruction (MPR), and volume rendering (VR) imaging. VV development was evaluated by the VV area/volume ratio, defined as the VV area/volume divided by the adventitial area/volume. Compared to the control group, the observed VV number and diameter on 3D images of MPR and VR were significantly higher, and curved and torturous-shaped VV were more frequently observed in the BDG and Fontan groups (P < 0.001, all). The median VV volume ratio was significantly greater in the BDG than in the control group (3.38% vs. 0.61%; P < 0.001). Although the VV volume ratio decreased significantly after the Fontan procedure (2.64%, P = 0.005 vs. BDG), the ratio remained higher than in the control group (P < 0.001 vs. control).

Conclusion

3D OCT imaging is a novel method that can be used to evaluate adventitial PA VV and may provide pathophysiological insight into the role of the PA VV in these patients.
Long-term persistence and adherence with non-vitamin K oral anticoagulants in patients with atrial fibrillation and their associations with stroke risk
Authors: Komen Joris J , Heerdink Eibert R , Klungel Olaf H , Mantel-Teeuwisse Aukje K , Forslund Tomas , Wettermark Björn , Hjemdahl Paul
Published: April 2020

Aims 

Studies on adherence and persistence with non-vitamin K oral anticoagulant (NOAC) treatment have relied on data from the early years of NOAC availability. We aimed to study long-term adherence and persistence with NOACs and their association with stroke risk.

Methods and results 

From the Stockholm Healthcare database, we included 21 028 atrial fibrillation patients claiming a first NOAC prescription from July 2011 until October 2018, with more than 1000 patients having more than 5 years of follow-up (median: 2.0, interquartile range: 1.0–3.2). Persistence rates, defined as continuing to claim NOAC prescriptions within a 90-day gap, decreased to 70% at the end of follow-up. However, 85% of the patients were treated at the end of the study due to reinitiations. Adherence, calculated as medication possession rate (MPR) in 3 and 6-month intervals among persistent users, remained stable at 90%, with 75% of patients having an MPR >95% throughout the study period. Using a case–control design, we calculated associations of persistence and adherence with stroke risk, adjusting for potential confounders. The outcome was a composite of ischaemic or unspecified stroke and transient ischaemic attack. Non-persistence and poor adherence were both associated with increased stroke risk [non-persistence adjusted odds ratio (aOR): 2.05; 95% confidence interval (CI): 1.49–2.82, 1% reduction MPR aOR: 1.03; CI: 1.01–1.05]. There was no association between non-persistence or poor adherence and the falsification endpoints; fractions and respiratory infections, indicating no ‘healthy-adherer’ effect.

Conclusion 

Persistence rates decreased slowly over time, but persistent patients had high adherence rates. Both non-persistence and poor adherence were associated with an increased stroke risk.
Differential Effects of Long-Term Caloric Restriction and Dietary Protein Source on Bone and Marrow Fat of the Aging Rat
Authors: Duque Gustavo , Al Saedi Ahmed , Rivas Daniel , Miard Stéphanie , Ferland Guylaine , Picard Frederic , Gaudreau Pierrette
Published: April 2020

Long-term caloric restriction (CR) has been shown to be beneficial to various tissues and organs. In contrast, CR exerts differential effects on bone, which could be due in part to the nature of the protein regime utilized. Male Sprague Dawley rats (8-month-old) were subjected for 12 months to 40% CR in macronutrients and compared with rats fed ad libitum for the same period. Casein- and soy-fed groups were compared. There was a significant decrease in bone quality in both CR groups, which was independent of the source of protein in the diet. In contrast, the group fed soy protein ad libitum showed better bone quality and higher levels of bone formation compared with casein-fed animals. Notably, bone marrow adipocytes were not mobilized upon CR as demonstrated by an absence of change in adipocyte number and tissue expression of leptin. This study demonstrates that the negative effect of CR on bone quality could not be prevented by the most common protein regimes.
Parametric analysis of the elastohydrodynamic lubrication efficiency on induced seismicity
Authors: Cornelio Chiara , Violay Marie
Published: April 2020

During reservoir stimulations, the injection of fluids with variable viscosities can trigger seismicity. Several fault lubrication mechanisms have been invoked to explain the dynamic stress drop occurring during those seismic events. Here, we perform a parametric analysis of the elastohydrodynamic fault lubrication mechanism to assess its efficiency during fluid-induced earthquakes. The efficiency of the mechanism is measured with the dimensionless Sommerfeld number S. Accordingly, we analysed eight well-documented cases of induced seismicity associated with the injection of fluids whose viscosities range from 1 mPa s (water) to 100 mPa s (proppant). We collected information related to the in situ stress field, fault orientation and geometry, moment of magnitude and static stress drop of the events. These parameters allow us to analyse the variation in the Sommerfeld number. Our results show that the estimated dynamic friction on the fault during the event is compatible with the fault weakening predicted by the elastohydrodynamic lubrication theory, particularly for highly viscous fluids.
Effect of a prospective payment method for health facilities on direct medical expenditures in a low-resource setting: a paired pre-post study
Authors: Meda Ivlabèhiré Bertrand , Kouanda Seni , Dumont Alexandre , Ridde Valéry
Published: April 2020

Almost all sub-Saharan countries have adopted cost-reduction policies to facilitate access to health care. However, several studies underline the reimbursement delays experienced by health facilities, which lead to deficient implementation of these policies. In April 2016, for its free care policy, Burkina Faso shifted from fee-for-service (FFS) paid retrospectively to FFS paid prospectively. This study tested the hypothesis that this new method of payment would be associated with an increase in direct medical expenditures (expenses covered by the policies) associated with deliveries. This paired pre-post study used data from two cross-sectional national surveys. Observations were paired according to the health facility and the type of delivery. We used a combined approach (state and household perspectives) to capture all direct medical expenses (delivery fees, drugs and supplies costs, paraclinical exam costs and hospitalization fees). A Wilcoxon signed-rank test was used to test the hypothesis that the 2016 distribution of direct medical expenditures was greater than that for 2014. A total of 279 pairs of normal deliveries, 66 dystocia deliveries and 48 caesareans were analysed. The direct medical expenditure medians were USD 4.97 [interquartile range (IQR): 4.30–6.02], 22.10 [IQR: 15.59–29.32] and 103.58 [IQR: 85.13–113.88] in 2014 vs USD 5.55 [IQR: 4.55–6.88], 23.90 [IQR: 17.55–48.81] and 141.54 [IQR: 104.10–172.02] in 2016 for normal, dystocia and caesarean deliveries, respectively. Except for dystocia (P = 0.128) and medical centres (P = 0.240), the 2016 direct medical expenditures were higher than the 2014 expenses, regardless of the type of delivery and level of care. The 2016 expenditures were higher than the 2014 expenditures, regardless of the components considered. In the context of cost-reduction policies in sub-Saharan countries, greater attention must be paid to the provider payment method and cost-control measures because these elements may generate an increase in medical expenditures, which threatens the sustainability of these policies.
Rapid development of telehealth capabilities within pediatric patient portal infrastructure for COVID-19 care: barriers, solutions, results
Authors: Patel Pious D , Cobb Jared , Wright Deidre , Turer Robert W , Jordan Tiffany , Humphrey Amber , Kepner Adrienne L , Smith Gaye , Rosenbloom S Trent
Published: April 2020

The COVID-19 national emergency has led to surging care demand and the need for unprecedented telehealth expansion. Rapid telehealth expansion can be especially complex for pediatric patients. From the experience of a large academic medical center, this report describes a pathway for efficiently increasing capacity of remote pediatric enrollment for telehealth while fulfilling privacy, security, and convenience concerns.

The design and implementation of the process took 2 days. Five process requirements were identified: efficient enrollment, remote ability to establish parentage, minimal additional work for application processing, compliance with guidelines for adolescent autonomy, and compliance with institutional privacy and security policies.

Weekly enrollment subsequently increased 10-fold for children (age 0–12 years) and 1.2-fold for adolescents (age 13–17 years). Weekly telehealth visits increased 200-fold for children and 90-fold for adolescents.

The obstacles and solutions presented in this report can provide guidance to health systems for similar challenges during the COVID-19 response and future disasters.
Bilastine: Quantitative Determination by LC with Fluorescence Detection and Structural Elucidation of the Degradation Products Using HRMS
Authors: Motta Paola Ribeiro , dos Santos Porto Douglas , Martini Paulo Roberto Rodrigues , Bajerski Lisiane , Azeredo Juliano Braun , Paula Fávero Reisdorfer , Paim Clésio Soldateli
Published: April 2020

Background

A liquid chromatography (LC) stability-indicating method was developed and validated for the quantitative determination of bilastine in coated tablets.

Objective

The procedure was validated for specificity, linearity, robustness, precision, and accuracy. Plackett-Burmann experimental design was used to determine the robustness of the method.

Method

Chromatographic separation was performed on a Shim-pack® RP-18 column with fluorescence detection. The degradation products formed under oxidative conditions were isolated and identified using high-resolution mass spectrometry (HRMS). In silico prediction of degradation products and in silico toxicity studies were also performed.

Results

The LC method presented good recovery and precision (intraday and interday), the response was linear in a range of 0.20 to 0.70 μg mL−1, and the results demonstrated the robustness of the analytical method under the evaluated conditions.

Conclusions

The degradation products were identified as benzimidazole (DP1) and amine N-oxide of bilastine (DP2). The results for the toxicity studies demonstrated the high mutagenic potential of DP1 and hepatotoxicity and hERG I inhibitor effects of DP2.

Highlights

Bilastine degradation products were identified as benzimidazole and amine N-oxide using HRMS.
Breast Imaging and Image-guided Intervention in Tanzania: Initial Experience
Authors: Okello Roselyne , Rooney Timothy B , Jumbe Mwajuma , Sakafu Lulu , Koch Troy , Laage-Gaupp Fabian , Minja Frank , Chamberlin Mary
Published: April 2020

Breast imaging capacity in Tanzania is currently very limited. In a country of almost 60 million people, mammographic units are exceedingly rare. The few existing units are compromised by lack of maintenance and quality control and extremely limited technologist training. Breast cancer incidence continues to increase in East Africa, while the ability to accurately diagnose and differentiate benign and malignant breast disease remains a challenge. However, as ultrasound technology improves and becomes more affordable, there is increased access to devices including hand-held point of care ultrasound. Additionally, there has been a recent expansion in the training of academic radiologists in Tanzania, creating an opportunity for possible sustainable improvement of breast imaging and intervention. Our initial efforts at the Muhimbili Academic Medical Center (MAMC) included social media advertising for symptomatic and asymptomatic women, followed by screening (clinical breast exam) and subsequent ultrasound imaging of symptomatic women. We then initiated a workflow for ultrasound-guided breast intervention, performed biopsies, reviewed results by local pathologists, and brought the postbiopsy patients back for radiologic–pathologic correlation, wound assessment, and coordination of follow-up and treatment.
Using IPM-CPR as a Management Program for Apple Orchards
Authors: Akotsen-Mensah C , Blaauw B , Short B , Leskey T C , Bergh J C , Polk D , Nielsen A L
Published: April 2020

We have demonstrated how management of key orchard pests including the insect invasive species Halyomorpha halys (Stål) (Hemiptera: Pentatomidae) can be accomplished using a systems-level approach termed IPM-CPR (Integrated Pest Management-Crop Perimeter Restructuring) in apple. We conducted on-farm comparisons of IPM-CPR to standard management program for managing H. halys, Cydia pomonella (L.) (Lepidoptera: Tortricidae), Grapholita molesta (Busck) (Lepidoptera: Tortricidae), and Lygus lineolaris Palisot de Beauvois (Hemiptera: Miridae) in commercial apple orchards in 2014, 2016, and 2017 in New Jersey, Maryland, and Virginia. The presence and abundance of key pests and fruit injury at harvest were used as a measure of success of the program. We compared the amount of insecticide applied for each management program. In majority of instances, there were no differences in the IPM-CPR and the standard management program in terms of H. halys numbers in baited pyramid traps and stink bug injury at harvest. Damage from C. pomonella and G. molesta in the IPM-CPR treatment was significantly lower than the standard management program in 2014 and 2017. Amount of active ingredient used was on average 62.1% lower in the IPM-CPR treatment compared with standard management program. Despite a reduction in insecticide use, there were minimal impacts on beneficial insects. Overall, IPM-CPR in apples successfully managed key orchard pests, including H. halys, and used significantly less insecticide than a standard insecticide-based management program and could be adopted as a systems-level approach for pest population reduction.
Outcomes after thoracoscopic surgery in octogenarian patients with clinical N0 non-small-cell lung cancer
Authors: Nakao Masayuki , Ichinose Junji , Matsuura Yosuke , Okumura Sakae , Mun Mingyon
Published: April 2020

Objective

The number of surgeries for elderly patients with lung cancer is increasing. In our institute, thoracoscopic lobectomy and hilar lymph node dissection are the standard procedure for octogenarian patients with clinical N0 non-small-cell lung cancer. The aim of this study was to determine the outcome of our strategy for octogenarian patients.

Methods

Seventy octogenarian patients with clinical N0 non-small-cell lung cancer who underwent surgery were enrolled (O group). As a control group, 205 septuagenarian patients were also enrolled (S group). We compared several clinicopathological factors and outcomes.

Results

The median age of the O group was 82. There was no significant difference in the comorbidity ratio between the two groups. The 5-year overall survival ratio for the O group (72.8%) was significantly worse than that for the S group (88.3%). However, multivariate analysis proved age was not an independent predictor of outcome. The rates of recurrences involving ipsilateral mediastinal lymph nodes were equal in the two groups. After propensity score matching, clinical T1 patients were dominant (85%) in two matched group and no statistically significant differences were observed in the 5-year overall survival between the two groups.

Conclusions

Our strategy for octogenarian patients with non-small-cell lung cancer, including omission of mediastinal lymph node dissection, was determined to be feasible, in particularly with cT1N0 disease.
Hippocampal Lipocalin 2 Is Associated With Neuroinflammation and Iron-Related Oxidative Stress in ob/ob Mice
Authors: Jin Zhen , Kim Kyung Eun , Shin Hyun Joo , Jeong Eun Ae , Park Kyung-Ah , Lee Jong Youl , An Hyeong Seok , Choi Eun Bee , Jeong Jae Hun , Kwak Woori , Roh Gu Seob
Published: April 2020

Obesity causes brain injuries with inflammatory and structural changes, leading to neurodegeneration. Although increased circulating lipocalin 2 (LCN2) level has been implicated in neurodegenerative diseases, the precise mechanism of neurodegeneration in obesity is not clear. Here, we investigated whether LCN2-mediated signaling promotes neurodegeneration in the hippocampus of leptin-deficient ob/ob mice, which are characterized by obesity, insulin resistance, systemic inflammation, and neuroinflammation. In particular, there was significant upregulation of both LCN2 and matrix metalloproteinase 9 levels from serum and hippocampus in ob/ob mice. Using RNA-seq analysis, we found that neurodegeneration- sortilin-related receptor 1 (Sorl1) and brain-derived neurotrophic factor (Bdnf) genes were significantly reduced in the hippocampus of ob/ob mice. We additionally found that the endosome-related WD repeat and FYVE-domain-containing 1 (Wdfy1) gene were upregulated in ob/ob mice. In particular, iron overload-related mitochondrial ferritin and nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) proteins were increased in the hippocampus of ob/ob. Thus, these findings indicate that iron-binding protein LCN2-mediated oxidative stress promotes neurodegeneration in ob/ob mice.
Caffeine Use and Associations With Sleep in Adolescents With and Without ADHD
Authors: Cusick Caroline N , Langberg Joshua M , Breaux Rosanna , Green Cathrin D , Becker Stephen P
Published: April 2020

Objective

The objective of this study was to compare caffeine consumption in the morning, afternoon, and evening in adolescents with and without attention-deficit/hyperactivity disorder (ADHD) and examine associations with sleep functioning.

Methods

Participants were 302 adolescents (ages 12–14) with (N = 140) and without (N = 162) ADHD. Adolescents wore actigraph watches to assess total sleep time and wake after sleep onset and reported on sleep–wake problems and the number of caffeinated beverages consumed per day in the morning, afternoon, and evening. Parents reported on adolescents’ difficulties initiating and maintaining sleep. Chi-square tests, odds ratios, and path analyses were conducted.

Results

Analyses controlled for sex, medication status, and pubertal development. Adolescents with ADHD were 2.47 times more likely to consume caffeine in the afternoon and evening than adolescents without ADHD. Path analyses indicated significant associations between afternoon caffeine use and more self-reported sleep problems for adolescents with and without ADHD, and an association between evening caffeine use and self-reported sleep problems only in adolescents with ADHD. Afternoon caffeine use was associated with parent-reported sleep problems in adolescents with ADHD only. Caffeine use was not associated with actigraphy-assessed sleep.

Conclusion

This is the first study to show that adolescents with ADHD consume more caffeine than peers during later times of the day. Additionally, caffeine use is more consistently associated with poorer subjective sleep functioning in adolescents with ADHD. Pediatricians and mental health professionals should assess for caffeine use in adolescents with ADHD and co-occurring sleep problems.
Kilonova rates from spherical and axisymmetrical models
Authors: Kóbori József , Bagoly Zsolt , Balázs Lajos G
Published: April 2020

Detecting the thermal emission from double neutron star merger events is a challenging task because of the quick fading of the observed flux. In order to create an efficient observing strategy for their observing method, it is crucial to know their intrinsic rate. Unfortunately, the numerous models existing today predict this rate on a very wide range. Hence, our goal in this paper is to investigate the effect of different levels of approximations on the relative rate predictions. Also, we study the effect of distinct ejecta mass layouts on the light curve. We find that the ratio of the expected kilonova detections of the spherical to axisymmetrical models is 6:1 (or 2:1, depending on the input parameter set applied in our work). Nevertheless, the light-curve shape is only slightly affected by the various ejecta alignments. This means that different ejecta layouts can produce light curves with similar shapes making it a challenging task to infer the structure of the matter outflow. Thus, we conclude that the uncertainty in the rate predictions arising from the various ejecta mass distribution models is negligible compared to the errors present in other input parameters (e.g. binary neutron star merger rate). In addition, we show that up to moderate redshifts (z ≲ 0.2) the redshift distribution type (observed or uniform in volume) does not affect the expected relative rate estimations.
Role of ambient wavelength, shell size and pigmentation intensity in the heating of Mediterranean Theba pisana (Eupulmonata: Helicidae)
Authors: Tull Tatjana , Schmidt Danina , Köhler Heinz-R
Published: April 2020

Theba pisana is a polymorphic land snail widely used in ecophysiological research on the biological significance of solar irradiation. We investigated whether, taking size into account, differently pigmented morphs of a Mediterranean population of T. pisana influence the snails’ heating under different wavelengths. We used a laboratory set-up comprising light-emitting diodes emitting visible light of defined wavelengths and quantified shell heating using high-resolution thermography. Shell pigmentation was quantified densitometrically. There were significant effects of both shell size and light wavelength, such that small snails heated more than large ones over 15 min, and blue light (470 nm) raised temperature more than green light (525 nm). Pigmentation alone did not show significance, but a trend towards higher temperature with increasing pigmentation was evident. Despite the observed significances and trends, we could only explain at most 4.67% of variation in shell heating by multiple regression modelling. However, the light intensity used in this experiment was low and the pigmentation intensity of the shells varied, at most, by a factor of 2. This suggests the actual temperature of a snail depends not only on the tested variables, but also on the multifactorial action of a number of unknown, perhaps intrinsic physiological parameters.
Phase-plate cryo-EM structure of the Widom 601 CENP-A nucleosome core particle reveals differential flexibility of the DNA ends
Authors: Boopathi Ramachandran , Danev Radostin , Khoshouei Maryam , Kale Seyit , Nahata Sunil , Ramos Lorrie , Angelov Dimitar , Dimitrov Stefan , Hamiche Ali , Petosa Carlo , Bednar Jan
Published: April 2020

The histone H3 variant CENP-A marks centromeres epigenetically and is essential for mitotic fidelity. Previous crystallographic studies of the CENP-A nucleosome core particle (NCP) reconstituted with a human α-satellite DNA derivative revealed both DNA ends to be highly flexible, a feature important for CENP-A mitotic functions. However, recent cryo-EM studies of CENP-A NCP complexes comprising primarily Widom 601 DNA reported well-ordered DNA ends. Here, we report the cryo-EM structure of the CENP-A 601 NCP determined by Volta phase-plate imaging. The data reveal that one (‘left’) 601 DNA end is well ordered whereas the other (‘right’) end is flexible and partly detached from the histone core, suggesting sequence-dependent dynamics of the DNA termini. Indeed, a molecular dynamics simulation of the CENP-A 601 NCP confirmed the distinct dynamics of the two DNA extremities. Reprocessing the image data using two-fold symmetry yielded a cryo-EM map in which both DNA ends appeared well ordered, indicating that such an artefact may inadvertently arise if NCP asymmetry is lost during image processing. These findings enhance our understanding of the dynamic features that discriminate CENP-A from H3 nucleosomes by revealing that DNA end flexibility can be fine-tuned in a sequence-dependent manner.
Generation and validation of structurally defined antibody–siRNA conjugates
Authors: Nanna Alex R , Kel’in Alexander V , Theile Christopher , Pierson Justin M , Voo Zhi Xiang , Garg Ashish , Nair Jayaprakash K , Maier Martin A , Fitzgerald Kevin , Rader Christoph
Published: April 2020

Gene silencing by RNA interference (RNAi) has emerged as a powerful treatment strategy across a potentially broad range of diseases. Tailoring siRNAs to silence genes vital for cancer cell growth and function could be an effective treatment, but there are several challenges which must be overcome to enable their use as a therapeutic modality, among which efficient and selective delivery to cancer cells remains paramount. Attempts to use antibodies for siRNA delivery have been reported but these strategies use either nonspecific conjugation resulting in mixtures, or site-specific methods that require multiple steps, introduction of mutations, or use of enzymes. Here, we report a method to generate antibody–siRNA (1:2) conjugates (ARCs) that are structurally defined and easy to assemble. This ARC platform is based on engineered dual variable domain (DVD) antibodies containing a natural uniquely reactive lysine residue for site-specific conjugation to β-lactam linker-functionalized siRNA. The conjugation is efficient, does not compromise the affinity of the parental antibody, and utilizes chemically stabilized siRNA. For proof-of-concept, we generated DVD-ARCs targeting various cell surface antigens on multiple myeloma cells for the selective delivery of siRNA targeting β-catenin (CTNNB1). A set of BCMA-targeting DVD-ARCs at concentrations as low as 10 nM revealed significant CTNNB1 mRNA and protein knockdown.
Quality of supervisor behaviour, workplace social capital and psychological well-being
Authors: Kizuki Masashi , Fujiwara Takeo
Published: April 2020

Background

Employees with a higher level of workplace social capital (i.e. relationships, trust and reciprocity at work) have a lower risk of mental health problems. Supervisor behaviour may be a predictor of workplace social capital.

Aims

To examine the associations between supervisor behaviour, workplace social capital and psychological well-being.

Methods

We conducted a secondary analysis of the sixth European Working Conditions Survey. The study sample included 28 900 employees in 35 European countries with an immediate line manager. Depression was assessed with the WHO-5 Well-Being Index. Supervisor behaviour quality and workplace social capital were each measured with a 6-item question. Association between quality of supervisor behaviour and workplace social capital was analysed using a hierarchical linear modelling. A mediation analysis was conducted by using hierarchical logistic models of depression with and without workplace social capital index.

Results

A higher supervisor behaviour quality index was associated with an increased workplace social capital index (β, 0.55; 95% confidence interval [CI], 0.51–0.59). A higher workplace social capital index was associated with lower odds of depression (odds ratio [OR], 0.89; 95% CI, 0.87–0.90). A higher supervisor behaviour quality index was associated with lower odds of depression (OR, 0.90; 95% CI, 0.89–0.92); 58% of the effect was mediated by workplace social capital.

Conclusions

Our findings support the hypothesis that better supervisor behaviour quality increases workplace social capital and contributes to psychological well-being of employees. This may be useful for planning organizational interventions to enhance mental health of workers.
Emotional Awareness and Expression Therapy Achieves Greater Pain Reduction than Cognitive Behavioral Therapy in Older Adults with Chronic Musculoskeletal Pain: A Preliminary Randomized Comparison Trial
Authors: Yarns Brandon C , Lumley Mark A , Cassidy Justina T , Steers W Neil , Osato Sheryl , Schubiner Howard , Sultzer David L
Published: April 2020

Objective

Emotional awareness and expression therapy (EAET) emphasizes the importance of the central nervous system and emotional processing in the etiology and treatment of chronic pain. Prior trials suggest EAET can substantially reduce pain; however, only one has compared EAET with an established alternative, demonstrating some small advantages over cognitive behavioral therapy (CBT) for fibromyalgia. The current trial compared EAET with CBT in older, predominately male, ethnically diverse veterans with chronic musculoskeletal pain.

Design

Randomized comparison trial.

Setting

Outpatient clinics at the West Los Angeles VA Medical Center.

Subjects

Fifty-three veterans (mean age = 73.5 years, 92.4% male) with chronic musculoskeletal pain.

Methods

Patients were randomized to EAET or CBT, each delivered as one 90-minute individual session and eight 90-minute group sessions. Pain severity (primary outcome), pain interference, anxiety, and other secondary outcomes were assessed at baseline, post-treatment, and three-month follow-up.

Results

EAET produced significantly lower pain severity than CBT at post-treatment and follow-up; differences were large (partial η2 = 0.129 and 0.157, respectively). At post-treatment, 41.7% of EAET patients had >30% pain reduction, one-third had >50%, and 12.5% had >70%. Only one CBT patient achieved at least 30% pain reduction. Secondary outcomes demonstrated small to medium effect size advantages of EAET over CBT, although only post-treatment anxiety reached statistical significance.

Conclusions

This trial, although preliminary, supports prior research suggesting that EAET may be a treatment of choice for many patients with chronic musculoskeletal pain. Psychotherapy may achieve substantial pain reduction if pain neuroscience principles are emphasized and avoided emotions are processed.
Improved ligand-binding- and signaling-competent human NK2R yields in yeast using a chimera with the rat NK2R C-terminus enable NK2R-G protein signaling platform
Authors: Jain Abhinav R , Britton Zachary T , Markwalter Chester E , Robinson Anne S
Published: April 2020

The tachykinin 2 receptor (NK2R) plays critical roles in gastrointestinal, respiratory and mental disorders and is a well-recognized target for therapeutic intervention. To date, therapeutics targeting NK2R have failed to meet regulatory agency approval due in large part to the limited characterization of the receptor-ligand interaction and downstream signaling. Herein, we report a protein engineering strategy to improve ligand-binding- and signaling-competent human NK2R that enables a yeast-based NK2R signaling platform by creating chimeras utilizing sequences from rat NK2R. We demonstrate that NK2R chimeras incorporating the rat NK2R C-terminus exhibited improved ligand-binding yields and downstream signaling in engineered yeast strains and mammalian cells, where observed yields were better than 4-fold over wild type. This work builds on our previous studies that suggest exchanging the C-termini of related and well-expressed family members may be a general protein engineering strategy to overcome limitations to ligand-binding and signaling-competent G protein-coupled receptor yields in yeast. We expect these efforts to result in NK2R drug candidates with better characterized signaling properties.
Immune responses after influenza vaccination in patients of primary Sjögren’s syndrome
Authors: Zhou Xingyu , Liu Yisi , Jin Yuebo , Wang Yifan , Miao Miao , Chen Jiali , Cheng Yaobin , Liu Yudong , He Jing , Li Zhanguo
Published: April 2020

Objectives

Influenza vaccination is effective in preventing infections in most people. This study aimed to assess the changes of immune responses in primary Sjögren’s Syndrome (pSS) patients after influenza vaccination and determine the safety of influenza vaccination.

Methods

A total of 17 patients with pSS and 16 healthy controls (HCs) were included. Peripheral mononuclear cells were analysed by flow cytometry. Vaccine-specific antibodies were determined by ELISA. Clinical features and serological responses were monitored.

Results

The percentages of T follicular helper cell (Tfh) were significantly elevated in HCs after vaccination (P=0.0005), while no significant differences in the levels of Tfh in pSS patients were identified (P=0.1748). The proportions of Th2 cells were significantly decreased after vaccination in both pSS patients and HCs (P<0.05). In contrast, the percentages of Th1 cells and Th17 cells were significantly increased after vaccination in pSS patients (P<0.05), while no significant differences in the percentages of Th1 and Th17 cells were identified in HCs (P>0.05), although a trend towards higher levels of Th1 cells was observed (P=0.0830). No significant changes in the proportions of memory B cells and plasmablasts were observed after vaccination. Patients with pSS developed higher levels of vaccine-specific IgGs compared with HCs (P=0.001). No significant changes in disease manifestations and laboratory parameters were observed after vaccination. No increased vaccination related adverse effect was observed in pSS.

Conclusion

Our findings suggest the feasibility of applying influenza vaccines to patients with pSS, raising awareness for vaccination among the rheumatology community and involved healthcare professionals.
Combating antibiotic resistance using plant‐derived compounds
Authors: Jones Emily Marie , Lopper Matthew
Published: April 2020

Bacteria have steadily developed defenses against antibiotics since the world’s first fleet of antibacterial drugs was introduced. One strategy that bacteria can use to become multi‐drug resistant involves the overexpression of large, membrane‐embedded efflux pumps, such as the AcrAB‐TolC pump found in Escherichia coli (E. coli) and other Gram‐negative bacteria. This large efflux pump gives the bacterium the capability of transporting a wide variety of compounds out of the cell, including antibiotics that we use to combat bacterial infections. Overexpression of efflux pumps has been shown to lead to multidrug resistance in clinically important bacterial pathogens. Here, I have sought to identify novel inhibitors of bacterial efflux pumps by screening methanolic plant extracts for efflux pump inhibitory activity using an ethidium bromide‐based fluorescence assay. I have determined that yerba maté extract causes accumulation of ethidium bromide in live E. coli bacterial cells. To determine the ability of yerba maté extract to cause accumulation of clinically relevant antibiotics, I used growth curve analysis of E. coli in the presence of the plant extract with levofloxacin and carbenicillin. I have concluded that the combination of yerba maté and antibiotics enhances the susceptibility of bacteria. This research could open up a new avenue in the treatment of multi‐drug resistant bacterial infections.

Support or Funding Information

Clare Boothe Luce Research Scholars Program