bluuebunny/crossref_metadata_2025 huggingface dataset:
Substantial thermoelectric enhancement achieved by manipulating the band structure and dislocations in Ag and La co-doped SnTe
Authors: Xu Wenjing , Zhang Zhongwei , Liu Chengyan , Gao Jie , Ye Zhenyuan , Chen Chunguang , Peng Ying , Bai Xiaobo , Miao Lei
Published: April 2021

Eco-friendly SnTe based thermoelectric materials are intensively studied recently as candidates to replace PbTe; yet the thermoelectric performance of SnTe is suppressed by its intrinsically high carrier concentration and high thermal conductivity. In this work, we confirm that the Ag and La co-doping can be applied to simultaneously enhance the power factor and reduce the thermal conductivity, contributing to a final promotion of figure of merit. On one hand, the carrier concentration and band offset between valence bands are concurrently reduced, promoting the power factor to a highest value of ∼2436 µW·m−1·K−2 at 873 K. On the other hand, lots of dislocations (∼3.16×107 mm−2) associated with impurity precipitates are generated, resulting in the decline of thermal conductivity to a minimum value of 1.87 W·m−1·K−1 at 873 K. As a result, a substantial thermoelectric performance enhancement up to zT ≈ 1.0 at 873 K is obtained for the sample Sn0.94Ag0.09La0.05Te, which is twice that of the pristine SnTe (zT ≈ 0.49 at 873 K). This strategy of synergistic manipulation of electronic band and microstructures via introducing rare earth elements could be applied to other systems to improve thermoelectric performance.
A posteriori error estimates for a multi-scale finite-element method
Authors: Ahmed Blal Khallih , Allam Brahim , Mghazli Zoubida
Published: April 2021

We are interested in the discretization of a diffusion problem with highly oscillating coefficient, by a multi-scale finite-element method (MsFEM). The objective of this method is to capture the multi-scale structure of the solution via local basis functions which contain the essential information on small scales. In this paper, we perform an a posteriori analysis of this discretization. The main result consists of building error indicators with respect to both small and large meshes used in this method. We present a numerical test in which the experiments are in good coherency with the results of analysis.
Experimental investigation of granular friction behaviors during reciprocating sliding
Authors: Zhang Xuejie , Sun Wei , Wang Wei , Liu Kun
Published: April 2021

Granular friction behaviors are crucial for understanding the ubiquitous packing and flow phenomena in nature and industrial production. In this study, a customized experimental apparatus that can simultaneously measure the time history of normal and tangential forces on the inside-shearing unit is employed to investigate the granular friction behaviors during a linear reciprocating sliding process. It is observed that the evolution behaviors of two normal forces distributed separately on the shearing unit can qualitatively reflect the effects of the force chain network. During the half-loop of the reciprocating sliding, the total normal force, which indicates the load-bearing capacity of the granular system, experiences the following typical stages: decreases abruptly and stabilizes momentarily, further decreases significantly to the minimum, gradually increases to the maximum, and then remains stable. These stages are associated closely with the relaxation, collapse, reconstruction, and stabilization of the force chain, respectively. Interestingly, the coefficient of friction (COF) can reach a stable value rapidly within the initial sliding stage and subsequently remain constant. The average COF within stable ranges decreases significantly with the external load G in the power-function form, G−0.5. Meanwhile, the COF increases slightly with the sliding velocity. Finally, a complete illustration of the dependences of the granular COF on the external load and sliding velocity is provided. Our study contributes to granular friction research by providing an innovative experimental approach for directly measuring the COF and implicitly correlating the evolution of the force chain network.
Stackelberg Game-Based Radio Resource Management Algorithm in an Urban Rail Transit Communication System
Authors: Shao Yingxia , Jiang Hailin , Zhao Hongli
Published: April 2021

Train-to-wayside (T2W) and train-to-train (T2T) communication modes may coexist in future train-centric communication-based train control (CBTC) systems. The feasibility of T2T communication in urban rail transit is analyzed first. Referring to the device-to-device (D2D) communication scenario in the general cellular network, this paper establishes a radio resource optimization model for the coexistence of train-to-train communication and train-to-wayside communication. With the aim of more efficient scheduling of radio time-frequency resources in the dedicated frequency band, we propose a Stackelberg game-based radio resource management algorithm based on the consideration of different service priorities of trains. The analysis and simulation results show that the proposed algorithm can effectively guarantee the performance of the system and improve the reliability of the CBTC system.
An Unusual Presentation of Pyelonephritis: Is It COVID-19 Related?
Authors: van ‘t Hof L. J. , Pellikaan L. , Soonawala D. , Roshani H.
Published: April 2021

In severe cases of COVID-19, late complications such as coagulopathy and organ injury are increasingly described. In milder cases of the disease, the exact time frame and causal path of late-onset complications have not yet been determined. Although direct and indirect renal injury by SARS-CoV-2 has been confirmed, hemorrhagic renal infection or coagulative problems in the urinary tract have not yet been described. This case report describes a 35-year-old female without relevant medical history who, five days after having recovered from infection with SARS-CoV-2, had an unusual course of acute pyelonephritis of the right kidney and persistent fever under targeted antibiotic treatment. A hemorrhagic ureteral obstruction and severe swollen renal parenchyma preceded the onset of fever and was related to the developing pyelonephritis. Sudden thrombotic venous occlusion in the right eye appeared during admission. Symmetrical paresthesia in the limbs in combination with severe lower back pain and gastro-intestinal complaints also occurred and remained unexplained despite thorough investigation. We present the unusual combination of culture-confirmed bacterial hemorrhagic pyelonephritis with a blood clot in the proximal right ureter, complicated by retinal vein thrombosis, in a patient who had recovered from SARS-CoV-2-infection five days before presentation. The case is suspect of a COVID-19-related etiology.
SLM Simulation and MonteCarlo Path Tracing for Computer-Generated Holograms
Authors: Magallón Juan , Blesa Alfonso , Serón Francisco
Published: April 2021

Computer holography is a growing research field that must pay attention to two main issues concerning computing effort: the visualization of a 3D virtual scene with photo-realistic quality and the bottleneck related to hologram digitizalition and visualization limits. This work shows a computational approach based on a Monte Carlo path-tracing algorithm, which accounts for both geometrical and physical phenomena involved in hologram generation, and, therefore, makes a feasible estimation of computing time costs. As these holograms also require yet unavailable visualization devices, their behavior needs to be simulated by computer techniques.
Measurements and Approximations for Submicron‐Aerosol Size Distribution Functions
Authors: Chkhetiani O. G. , Gledzer E. B. , Vazaeva N. V.
Published: April 2021

Results of field measurements taken in the near‐Caspian (2002, 2003, 2007, 2009, 2010, 2011, 2013, 2014, 2016 years) and near‐Aral sea (1998) deserts under the conditions of weak winds (almost in the absence of saltation processes) and strong heating of the land surface are given. These results show that the fine mineral dust aerosol (0.1–1 m) considerably contributes to the total aerosol content of the atmospheric surface layer under such conditions. The scaling of daytime mean size distribution at a height of 2 m is approximated by dependence , where changes from 4 to 6 for different years of measurements, in contrary to the law for fraction m. Different compositions of aerosol particles at m and m, including multicomponent fractions (less than m) may result in different probabilities of their integration and disintegration. It is hypothesized that the equilibrium distribution of submicron aerosol is a result of sequential disintegration of aerosol particles with a possibility for their reintegration. The simplest distribution approximations are given based on the Kolmogorov direct differential equation which is usually used in considering the Poisson distributions in equations for queuing systems.
Investigation of a Neutral “Tongue” Observed by GOLD During the Geomagnetic Storm on May 11, 2019
Authors: Cai Xuguang , Burns Alan G. , Wang Wenbin , Qian Liying , Solomon Stanley C. , Eastes Richard W. , McClintock William E. , Laskar F. I.
Published: April 2021

The National Aeronautics and Space Administration Global‐scale Observations of the Limb and Disk (GOLD) mission observed a unique structure of thermospheric column density ratio of O to N2 (∑O/N2) during a geomagnetic storm on day of year (DOY) 130 (May 10) to DOY 132 in 2019. The percentage difference of ∑O/N2 between the storm time (DOY 131) and the quiet time (DOY 128) had a relatively enhanced ∑O/N2 region sandwiched by two depleted regions over North America and the Atlantic Ocean in the Northern Hemisphere. This enhanced ∑O/N2 region is called the neutral tongue here. The National Center for Atmospheric Research Thermosphere Ionosphere Electrodynamics General Circulation Model also predicted a similar ∑O/N2 structure with the same spatial and temporal evolution as that seen in the GOLD observations on DOY 131. Model diagnostic analysis revealed that the neutral tongue was formed when the neutral wind in the region changed from mostly equatorward to poleward, which transported the ∑O/N2 rich air from lower latitudes into this longitude section, forming the neutral tongue. The neutral tongue separated a large depletion region formed earlier into two smaller depleted regions, one on each side of the neutral tongue.
Investigating the Relationship Between Peak Snow‐Water Equivalent and Snow Timing Indices in the Western United States and Alaska
Authors: Heldmyer A. , Livneh B. , Molotch N. , Rajagopalan B.
Published: April 2021

Understanding the distribution of snow‐water equivalent (SWE) is crucial for the prediction of water resources in the western United States. Backward running SWE reconstructions use satellite‐observed, binary snow presence imagery to reconstruct SWE mass estimates. This approach relies on the connection between snow timing and peak SWE, yet few studies have directly examined this relationship. Here, we investigate the strength and spatiotemporal variation in this relationship across the western United States and Alaska. Within the SNOTEL network (n = 611 sites), we find that most variance in peak SWE is explained (median R2 = 0.64, σ = 0.18) by, in order of explanatory skill, the timing of snow disappearance, onset, and cover duration, with variation in skill primarily related to climate conditions—like winter storm size and storm frequency—rather than topographical setting. We expand this analysis with a diagnostic model of peak SWE driven by remotely sensed snow timing indices applied to five hydrologically important regions in the western United States and Alaska. Uncertainties arising between blending point and 500 m grid‐scale observations were found to influence model SWE bias, but a robust correlation (median R = 0.88) with observations persisted across all tested thresholds. Overall, this supports the viability of snow timing information for quantifying spatial patterns of peak SWE (mean R2 = 0.76, percent bias = 3.6%) over the past two decades. These findings carry important implications for the development of SWE reanalysis products and for the evaluation of climate and hydrologic models.
Perspective on computational reaction prediction using machine learning methods in heterogeneous catalysis
Authors: Xu Jiayan , Cao Xiao-Ming , Hu P.
Published: April 2021

Machine learning algorithms can facilitate the reaction prediction in heterogeneous catalysis.
Comparison of therapeutic effects of combination therapy with prednisolone and tacrolimus or azathioprine on progressive interstitial pneumonia with systemic sclerosis
Authors: Kiboshi Takao , Kotani Takuya , Konma Junichi , Makino Hidehiko , Matsuda Shogo , Suzuka Takayasu , Wada Yumiko , Shiba Hideyuki , Hata Kenichiro , Shoda Takeshi , Takeuchi Tohru
Published: April 2021

Objectives

We retrospectively compared the therapeutic effects of combination therapy with prednisolone (PSL) and oral tacrolimus (TAC) or azathioprine (AZA) on progressive interstitial pneumonia with systemic sclerosis (SSc-PIP).

Methods

The effects of PSL (0.2–0.5 mg/kg/day) and TAC (3 mg/day) or AZA (1–2 mg/kg/day) therapies (n = 18) were evaluated for short (12 months) and long (36 months or more) periods.

Results

In the short period, IP improved in 6 and 5 patients and was stable in 12 and 13 patients in the TAC and AZA groups, respectively. In the long period, 11 patients were followed up in the TAC group and 12 in the AZA group. IP improved in 4 and 2 patients and was stable in seven and nine in the TAC and AZA groups, respectively. The rates of evolution of total fibrosis score, and those corrected by disease duration for the long period, in the TAC group were significantly lower than those in the AZA group (p = .017 and .025, respectively).

Conclusion

The inhibitory effect of PSL and TAC combination therapy on the progression of fibrosis in SSc-PIP may be superior to that of PSL and AZA in the long period.
Theoretical uncertainties on the extraction of in-medium NN cross sections by different Pauli blocking algorithms *
Authors: Chen Xiang , Zhang Yingxun , Li Zhuxia
Published: April 2021

Three typical Pauli blocking algorithms in quantum molecular dynamics type models are investigated in the nuclear matter, the nucleus, and heavy ion collisions. In nuclear matter, the blocking ratios obtained with the three algorithms are underestimated by 13%-25% compared to the corresponding analytical values. For a finite nucleus, spurious collisions occur around the surface of the nucleus owing to the defects of the Pauli blocking algorithms. In the simulations of heavy ion collisions, the uncertainty of stopping power arising from the different Pauli blocking algorithms is less than 5%. Furthermore, the in-medium effects of nucleon-nucleon (NN) cross sections on the nuclear stopping power are discussed. Our results show that the transport model calculations with free NN cross sections result in the stopping power decreasing with beam energy when the beam energy is less than 300 MeV/u. To increase or decrease the values of the stopping power, the transport model calculations need enhanced or suppressed model dependent in-medium NN cross sections that are expected to be smaller than the true in-medium NN cross sections.
Thromboelastography utilization for dabigatran reversal in a patient with acute kidney injury
Authors: Gilbert Brian W , Ott M Jacob , Philip George J
Published: April 2021

Purpose

This case report describes utilization of thromboelastography (TEG) in the setting of an acute major bleed in a patient on dabigatran who had concomitant acute kidney injury.

An 80-year-old female presented to the emergency department after a fall with complaints of pain in her knee, shoulder, and hip. Her medical history was significant for coronary artery disease, for which she took clopidogrel 75 mg daily, and atrial fibrillation, for which she took dabigatran 150 mg twice daily. The physical exam was remarkable for pain within the shoulder, hip, and knee, which had swelling and ecchymosis that extended into the right thigh. Given the possibility of compartment syndrome with multiple possible etiologies of coagulopathy, TEG and computed tomography angiography (CTa) of the right lower extremity were performed. The initial TEG showed prolonged R time and activated clotting time, indicating clotting factor dysfunction with no additional coagulopathy noted, including antiplatelet effects. On the basis of the TEG and CTa findings, it was decided to reverse dabigatran with 5 grams of idarucizumab. Approximately 1 hour after administration of idarucizumab, the patient was taken to interventional radiology where a limited angiogram of the right lower extremity showed no active extravasation. Because of the patient’s renal dysfunction and the possibility of rebound hypercoaguability, repeat TEG tests were ordered at 4 and 8 hours after the initial reversal to ensure clearance of idarucizumab-dabigatran complexes. The repeat TEG values showed complete reversal of the initial coagulopathy noted. During the admission, the patient required no blood transfusions or surgical interventions and all her initial laboratory results improved.

Conclusion

Serial TEG testing was successful at managing multiple coagulopathies in a patient at risk for trauma-induced compartment syndrome.
Strategies used to meet the challenges of mass COVID-19 vaccination by the pharmacy department in a large academic medical center
Authors: Li Quan , Norman Sarah , Guthrie Pauline , Gachoya Julianna , Sebakijje Justin , Leftridge Zetta , Willis Cynthia G , Kishore Anil , Breakenridge Margaret , Spence Clyde
Published: April 2021

Purpose

Highly effective coronavirus disease 2019 (COVID-19) vaccines have brought hope for ending the pandemic. Unprecedented mass vaccination started first among healthcare workers. The aim of this report is to describe key strategies undertaken by a large hospital pharmacy department to meet the challenges of preparing a large quantity of COVID-19 vaccine doses in a short period of time.

MedStar Washington Hospital Center (MWHC) was in the first group of hospitals in Washington, DC, to receive Pfizer-BioNTech vaccine in December 2020. The pharmacy department faced challenges including stringent vaccine storage requirements, a need for specific equipment and workflow, limited funding, and staffing constraints. The pharmacy department’s senior leaders defined pharmacy responsibilities, budgeted for equipment, participated in vaccination center design, and instructed pharmacy informatics personnel. The vaccine coordinators were appointed to oversee all vaccination-related operations. An ultra–low temperature freezer was installed 2 weeks before arrival of the first shipment of vaccine. All pharmacy order entry tools and operating procedures were standardized, and staff training and schedules were finalized by December 15. The first dose of the vaccine was administered on December 16 at the vaccination center. Pharmacy staff members dispensed the vaccine doses and monitored patients. By January 6, 2021, MWHC had vaccinated 3,812 employees with their first vaccine dose, with an average of 228 doses administered daily.

Conclusion

Key strategies such as systemic coordination, early preparation, detailed planning, operating procedure development, and staff education and engagement proved successful in facilitating preparation of thousands of COVID-19 vaccine doses for hospital employees within a short period of time.
Comparison of online learning designs during the COVID-19 pandemic within bioinformatics courses in higher education
Authors: Abrahamsson Sanna , Dávila López Marcela
Published: April 2021

Motivation

Due to the worldwide COVID-19 pandemic, new strategies had to be adopted to move from classroom-based education to online education, in a very short time. The lack of time to set up these strategies, hindered a proper design of online instructions and delivery of knowledge. Bioinformatics-related training and other onsite practical education, tend to rely on extensive practice, where students and instructors have a face-to-face interaction to improve the learning outcome. For these courses to maintain their high quality when adapted as online courses, different designs need to be tested and the students’ perceptions need to be heard.

Results

This study focuses on short bioinformatics-related courses for graduate students at the University of Gothenburg, Sweden, which were originally developed for onsite training. Once adapted as online courses, several modifications in their design were tested to obtain the best fitting learning strategy for the students. To improve the online learning experience, we propose a combination of: (i) short synchronized sessions, (ii) extended time for own and group practical work, (iii) recorded live lectures and (iv) increased opportunities for feedback in several formats.

Supplementary information

Supplementary data are available at Bioinformatics online.
A new-onset pulmonary artery stenosis in a young man: case report
Authors: Vanni Francesco , Scheggi Valentina , Marchionni Niccolò , Stefàno Pier Luigi
Published: April 2021

Background 

Poorly differentiated and undifferentiated sarcomas are the most common primary tumours of the pulmonary arteries. They usually affect large-calibre vessels and present with predominantly intraluminal growth. Dyspnoea, cough, chest pain, and haemoptysis are the most common presenting symptoms. Clinical and imaging manifestations can mimic pulmonary embolisms and correct diagnosis may require multimodal imaging. The overall prognosis is poor; however, early diagnosis and complete surgical resection seem to improve the prognosis.

Case summary 

A 31-year-old male was admitted to our department after a pre-syncopal episode associated with dyspnoea of recent onset. Echocardiography showed a mass with irregular borders attached to the pulmonary artery trunk, almost obliterating its lumen and determining a flow acceleration with a peak velocity and gradient, respectively, of 3.8 m/s and 60 mmHg. At cardiac magnetic resonance imaging and positron emission tomography-computed tomography scan, the mass had inhomogeneous contrast impregnation and an intense 18-fluorodeoxyglucose uptake, both findings are highly suggestive of an angiosarcoma of the pulmonary artery. Biopsy specimens were taken through bronchoscopy but the material was insufficient for diagnosis. The patient decided to continue treatment in another hospital, where he died a few months later.

Discussion 

The presence of a unique mass involving the main trunk of the pulmonary artery or proximal branches associated with rapidly progressive dyspnoea in a patient at low risk for pulmonary embolism should raise the suspicion of primary sarcoma of the pulmonary artery. There are no guidelines for the treatment. Surgery and neo/adjuvant chemotherapy are reported in literature but burdened by bias and concerning a small number of cases.
Peritraumatic Plasma Omega-3 Fatty Acid Concentration Predicts Chronic Pain Severity Following Thermal Burn Injury
Authors: Mauck Matthew C , Barton Chloe E , Tungate Andrew S , Shupp Jeffrey W , Karlnoski Rachel , Smith David J , Williams Felicia N , Jones Samuel W , Sefton Christopher , McGrath Kyle , Cairns Bruce A , McLean Samuel A
Published: April 2021

Chronic pain is a significant comorbidity of burn injury affecting up to 60% of survivors. Currently, no treatments are available to prevent chronic pain after burn injury. Accumulating evidence suggests that omega-3 fatty acids (O3FAs) improve symptoms across a range of painful conditions. In this study, we evaluated whether low peritraumatic levels of O3FA predict greater pain severity during the year after burn injury. Burn survivors undergoing skin autograft were recruited from three participating burn centers. Plasma O3FA (n = 77) levels were assessed in the early aftermath of burn injury using liquid chromatography/mass spectrometry, and pain severity was assessed via the 0 to 10 numeric rating scale for 1 year following burn injury. Repeated-measures linear regression analyses were used to evaluate the association between peritraumatic O3FA concentrations and pain severity during the year following burn injury. Peritraumatic O3FA concentration and chronic pain severity were inversely related; lower levels of peritraumatic O3FAs predicted worse pain outcomes (β = −0.002, P = .020). Future studies are needed to evaluate biological mechanisms mediating this association and to assess the ability of O3FAs to prevent chronic pain following burn injury.
Essentialism and Exclusion: Racism in Cancer Risk Prediction Models
Authors: Waters Erika A , Colditz Graham A , Davis Kia L
Published: April 2021

Cancer risk prediction models have the potential to revolutionize the science and practice of cancer prevention and control by identifying the likelihood that a patient will develop cancer at some point in the future, likely experience more benefit than harm from a given intervention, and survive their cancer for a certain number of years. The ability of risk prediction models to produce estimates that are valid and reliable for people from diverse socio-demographic backgrounds—and consequently their utility for broadening the reach of precision medicine to marginalized populations—depends on ensuring that the risk factors included in the model are represented as thoroughly and as accurately as possible. However, cancer risk prediction models created in the United States have a critical limitation, the origins of which stem from the country’s earliest days: they either erroneously treat the social construct of race as an immutable biological factor (ie, they “essentialize” race), or they exclude from the model those socio-contextual factors that are associated with both race and health outcomes. Models that essentialize race and/or exclude socio-contextual factors sometimes incorporate “race corrections” that adjust a patient’s risk estimate up or down based on their race. This commentary discusses the origins of race corrections, potential flaws with such corrections, and strategies for developing cohorts for developing risk prediction models that do not essentialize race or exclude key socio-contextual factors. Such models will help move the science of cancer prevention and control towards its goal of eliminating cancer disparities and achieving health equity.
Safe laparoscopic appendectomy in pregnant patient during active labor
Authors: Austin Charlotte S , Jaronczyk Michael
Published: April 2021

Appendectomy is the standard of care in pregnant patients with acute appendicitis. The use of laparoscopy in pregnant patients with acute appendicitis is still debated, especially for patients in their third trimester. We present a case of a patient who safely underwent a laparoscopic appendectomy during early labor and subsequently delivered a healthy baby. In the correct situations and hands, laparoscopy can likely be safely used throughout pregnancy.
ArabidopsisSMC6AandSMC6Bhave redundant function in seed and gametophyte development
Authors: Zou Wenxuan , Li Gang , Jian Liufang , Qian Jie , Liu Yantong , Zhao Jie
Published: April 2021

Reproductive development is a crucial process during plant growth. The structural maintenance of chromosome (SMC) 5/6 complex has been studied in various species. However, there are few studies on the biological function of SMC6 in plant development, especially during reproduction. In this study, knocking out of both AtSMC6A and AtSMC6B led to severe defects in Arabidopsis seed development, and expression of AtSMC6A or AtSMC6B could completely restore seed abortion in the smc6a-/-smc6b-/-double mutant. Knocking down AtSMC6A in the smc6b-/- mutant led to defects in female and male development and decreased fertility. The double mutation also resulted in loss of cell viability, and caused embryo and endosperm cell death through vacuolar cell death and necrosis. Furthermore, the expression of genes involved in embryo patterning, endosperm cellularisation, DNA damage repair, cell cycle regulation, and DNA replication were significantly changed in the albino seeds of the double mutant. Moreover, we found that the SMC5/6 complex may participate in the SOG1 (SUPPRESSOR OF GAMMA RESPONSE1)-dependent DNA damage repair pathway. These findings suggest that both AtSMC6A and AtSMC6B are functionally redundant and play important roles in seed and gametophyte development through maintaining chromosome stability in Arabidopsis.
Orchestration of plant development and defense by indirect crosstalk of salicylic acid and brassinosteorid signaling via transcription factor GhTINY2
Authors: Xiao Shenghua , Hu Qin , Zhang Xiaojun , Si Huan , Liu Shiming , Chen Lin , Chen Kun , Berne Sabina , Yuan Daojun , Lindsey Keith , Zhang Xianlong , Zhu Longfu
Published: April 2021

Salicylic acid (SA) and brassinosteroids (BRs) are well known to regulate diverse processes of plant development and stress responses, but the mechanisms by which these phytohormones mediate the growth and defense trade-off are largely unclear. In addition, little is known about the roles of DEHYDRATION RESPONSIVE ELEMENT BINDING transcription factors, especially in biotic stress and plant growth. Here, we identified a cotton (Gossypium hirsutum) APETALA2/ETHYLENE RESPONSIVE FACTOR gene GhTINY2 that is strongly induced by Verticillium dahliae. Overexpression of GhTINY2 in cotton and Arabidopsis enhanced tolerance to V. dahliae, while knockdown of expression increased the susceptibility of cotton to the pathogen. GhTINY2 was found to promote SA accumulation and SA signaling transduction by directly activating expression of WRKY51. Moreover, GhTINY2-overexpressing cotton and Arabidopsis showed retardation of growth, increased sensitivity to inhibitors of BR biosynthesis, down-regulation of several BR-induced genes, and up-regulation of BR-repressed genes, while GhTINY2-RNAi cotton showed the opposite effects. We further determined that GhTINY2 negatively regulates BR signaling by interacting with BRASSINAZOLE-RESISTANT 1 (BZR1) and restraining its transcriptional activation of the expression of INDOLE-3-ACETIC ACID INDUCIBLE 19 (IAA19). These findings indicate that GhTINY2 fine-tunes the trade-off between immunity and growth via indirect crosstalk between WRKY51-mediated SA biosynthesis and BZR1-IAA19-regulated BR signaling.
PERCEPTRON: an open-source GPU-accelerated proteoform identification pipeline for top-down proteomics
Authors: Khalid Muhammad Farhan , Iman Kanzal , Ghafoor Amna , Saboor Mujtaba , Ali Ahsan , Muaz Urwa , Basharat Abdul Rehman , Tahir Taha , Abubakar Muhammad , Akhter Momina Amer , Nabi Waqar , Vanderbauwhede Wim , Ahmad Fayyaz , Wajid Bilal , Chaudhary Safee Ullah
Published: April 2021

PERCEPTRON is a next-generation freely available web-based proteoform identification and characterization platform for top-down proteomics (TDP). PERCEPTRON search pipeline brings together algorithms for (i) intact protein mass tuning, (ii) de novo sequence tags-based filtering, (iii) characterization of terminal as well as post-translational modifications, (iv) identification of truncated proteoforms, (v) in silico spectral comparison, and (vi) weight-based candidate protein scoring. High-throughput performance is achieved through the execution of optimized code via multiple threads in parallel, on graphics processing units (GPUs) using NVidia Compute Unified Device Architecture (CUDA) framework. An intuitive graphical web interface allows for setting up of search parameters as well as for visualization of results. The accuracy and performance of the tool have been validated on several TDP datasets and against available TDP software. Specifically, results obtained from searching two published TDP datasets demonstrate that PERCEPTRON outperforms all other tools by up to 135% in terms of reported proteins and 10-fold in terms of runtime. In conclusion, the proposed tool significantly enhances the state-of-the-art in TDP search software and is publicly available at https://perceptron.lums.edu.pk. Users can also create in-house deployments of the tool by building code available on the GitHub repository (http://github.com/BIRL/Perceptron).
Sleep deprivation reduces vagal tone during an inspiratory endurance task in humans
Authors: Westphal Willy-Paul , Rault Christophe , Robert René , Ragot Stéphanie , Neau Jean-Philippe , Fernagut Pierre-Olivier , Drouot Xavier
Published: April 2021

Study Objectives

Sleep deprivation alters inspiratory endurance by reducing inspiratory motor output. Vagal tone is involved in exercise endurance. This study aimed to investigate the effect of sleep deprivation on vagal tone adaptation in healthy subjects performing an inspiratory effort.

Methods

Vagal tone was assessed using Heart Rate Variability normalized units of frequency domain component HF (high frequency) before, at the start, and the end of an inspiratory loading trial performed until exhaustion by 16 volunteers after one night of sleep deprivation and one night of normal sleep, where sleep deprivation reduced the inspiratory endurance by half compared to the normal sleep condition (30 min vs 60 min).

Results

At rest, heart rate was similar in sleep deprivation and normal sleep conditions. In normal sleep condition, heart rate increased during inspiratory loading task; this increase was greater in sleep deprivation condition. In normal sleep condition, vagal tone increased at the beginning of the trial. This vagal tone increase was absent in sleep deprivation condition.

Conclusions

Sleep deprivation abolished vagal tone response to inspiratory load, possibly contributing to a higher heart rate during the trial and to a reduced inspiratory endurance.

Clinical Trial Registration

NCT02725190.
Developmental and Intergenerational Landscape of Human Circulatory Lipidome and its Association with Obesity Risk
Authors: Mir Sartaj Ahmad , Chen Li , Burugupalli Satvika , Burla Bo , Ji Shanshan , Smith Adam Alexander T. , Narasimhan Kothandaraman , Ramasamy Adaikalavan , Tan Karen Mei-Ling , Huynh Kevin , Giles Corey , Mei Ding , Wong Gerard , Yap Fabian , Tan Kok Hian , Collier Fiona , Saffery Richard , Vuillermin Peter , Bendt Anne K. , Burgner David , Ponsonby Anne-Louise , Lee Yung Seng , Chong Yap Seng , Gluckman Peter D , Eriksson Johan G. , Meikle Peter J. , Wenk Markus R. , Karnani Neerja
Published: April 2021

Lipids play a vital role in human health and development, but changes to their circulatory levels during gestation and in early life are poorly understood. Here we present the first developmental and intergenerational landscape of the human circulatory lipidome, derived by profiling of 480 lipid species representing 25 lipid classes, in mothers and their offspring (n=2491). Levels of 66% of the profiled lipids increased in maternal circulation during gestation, while cord blood had higher concentrations of acylcarnitines and lysophospholipids. The offspring lipidome at age six years revealed striking similarities with postnatal maternal lipidome (adult) in its lipid composition and concentrations. Comparison of lipids associated with child and maternal adiposity identified a 92% overlap, implying intergenerational similarities in the lipid signatures of obesity risk. We also catalogued lipid signatures linked with maternal adiposity during gestation and offspring birthweight, and validated (>70% overlap) the findings in an independent birth-cohort (n=1935).
Convergent, functionally independent signaling by mu and delta opioid receptors in hippocampal parvalbumin interneurons
Authors: He Xinyi Jenny , Patel Janki , Weiss Connor E. , Ma Xiang , Bloodgood Brenda L. , Banghart Matthew R.
Published: April 2021

Functional interactions between G protein-coupled receptors are poised to enhance neuronal sensitivity to neuromodulators and therapeutic drugs. Mu and Delta opioid receptors (MORs and DORs) can interact when overexpressed in the same cells, but whether co-expression of endogenous MORs and DORs in neurons leads to functional interactions is unclear. Here, we show that both MORs and DORs inhibit parvalbumin-expressing basket cells (PV-BCs) in hippocampal CA1 through partially occlusive signaling pathways that terminate on somato-dendritic potassium channels and presynaptic calcium channels. Using photoactivatable opioid neuropeptides, we find that DORs dominate the response to enkephalin in terms of both ligand-sensitivity and kinetics, which may be due to relatively low expression levels of MOR. Opioid-activated potassium channels do not show heterologous desensitization, indicating that MORs and DORs signal independently. In a direct test for heteromeric functional interactions, the DOR antagonist TIPP-Psi does not alter the kinetics or potency of either the potassium channel or synaptic responses to photorelease of the MOR agonist DAMGO. Thus, despite largely redundant and convergent signaling, MORs and DORs do not functionally interact in PV-BCs. These findings imply that crosstalk between MORs and DORs, either in the form of physical interactions or synergistic intracellular signaling, is not a preordained outcome of co-expression in neurons.
A Panel of DiversePseudomonas aeruginosaClinical Isolates for Research and Development
Authors: Lebreton Francois , Snesrud Erik , Hall Lindsey , Mills Emma , Galac Madeline , Stam Jason , Ong Ana , Maybank Rosslyn , Kwak Yoon I. , Johnson Sheila , Julius Michael , Swierczewski Brett , Waterman Paige E. , Hinkle Mary , Jones Anthony , Lesho Emil , Bennett Jason W. , McGann Patrick
Published: April 2021

Pseudomonas aeruginosais a leading cause of community-acquired and hospital-acquired infections. Successful treatment is hampered by its remarkable ability to rapidly develop resistance to antimicrobial agents, mostly through mutation. In response, the World Health Organization listed carbapenem-resistantP. aeruginosaas a Priority 1 (Critical) pathogen for research and development of new treatments. A key resource in developing effective countermeasures is access to diverse and clinically relevant strains for testing. Herein we describe a panel of 100 diverseP. aeruginosastrains to support this endeavor.

Whole genome sequencing was performed on 3,785P. aeruginosahoused in our repository. Isolates were cultured from clinical samples collected from healthcare facilities around the world between 2003 and 2017. Core-genome multi-locus sequence typing and high-resolution SNP-based phylogenetic analyses were used to select a panel of 100 strains that captured the genetic diversity of this collection. Comprehensive antibiotic susceptibility testing was also performed using 14 clinically relevant antibiotics.

This 100-strain diversity panel contained representative strains from 91 different sequence-types, including genetically distinct isolates from major epidemic clones ST-111, ST-235, ST-244, and ST-253. Seventy-one distinct antibiotic susceptibility profiles were identified ranging from pan-sensitive to pan-resistant. Known resistance alleles as well as the most prevalent mutations underlying the antibiotic susceptibilities were characterized for all isolates.

This panel provides a diverse and comprehensive set ofP. aeruginosastrains for use in developing solutions to antibiotic resistance. The isolates, and all available meta-data including genome sequences, are available to industry, academic institutions, federal and other laboratories at no additional cost.

Importance

Pseudomonas aeruginosais one of the most important human pathogens and a leading target in the development of new drugs and therapeutics. This species displays a remarkable level of diversity and any potential therapeutic must contend with this characteristic to ensure it retains efficacy across different strains. To date, only limited panels ofP. aeruginosaare available for testing, and none have been designed to capture the genetic diversity of the species. The panel described herein has been designed to address this shortcoming by providing a set of 100 distinct strains that greatly captures the diversity of the species. This panel will be of significant value to research groups working on this important pathogen, both for research purposes and in the development of new diagnostics and countermeasures.
Multiple drug resistance in hookworms infecting greyhound dogs in the USA
Authors: Castro Pablo D. Jimenez , Venkatesan Abhinaya , Redman Elizabeth , Chen Rebecca , Malatesta Abigail , Huff Hannah , Zuluaga Salazar Daniel A. , Avramenko Russell , Gilleard John. S. , Kaplan Ray M.
Published: April 2021

The hookwormAncylostoma caninumis the most prevalent nematode parasite of dogs. Recently, we confirmed multiple-drug resistance (MDR) in severalA. caninumisolates to all anthelmintic drug classes approved for the treatment of hookworms in dogs in the United States (USA). Cases of MDR hookworms appear to be highly overrepresented in greyhounds, suggesting that the MDR worms evolved on racing greyhound farms/kennels. The aims of this study were to evaluate the range of drug-resistant phenotypes and genotypes of theA. caninuminfecting greyhounds. Fecal samples from recently retired greyhounds originating from geographically diverse areas of the USA were acquired from two greyhound adoption kennels, one active greyhound racing kennel, and three veterinary practices that work with adoption kennels. Fecal egg counts (FECs) were performed on fecal samples from 219 greyhounds, and despite almost all the dogs having been treated with one or more anthelmintics in the previous two to four weeks, the mean FEC was 822.4 eggs per gram (EPG). Resistance to benzimidazoles and macrocyclic lactones were measured using the egg hatch assay (EHA) and the larval development assay (LDA) respectively. We performed 23 EHA and 22 LDA on either individual or pooled feces, representing 81 animals. Mean and median IC50and IC95values for the EHA were 5.3 uM, 3.6 uM, and 24.5 uM, 23.4 uM respectively. For the LDA, mean and median IC50values were 749.8 nM, >1000 nM respectively. These values range from 62 to 68 times higher than those we measured in our susceptible laboratory isolates. Pre-treatment fecal samples could not be obtained, however, post-treatment samples representing 219 greyhounds were collected. For samples collected <10 days post-treatment with albendazole, moxidectin, or a combination of febantel-pyrantel-moxidectin, the mean FEC were 349, 333, and 835 EPG, respectively. Samples collected 10-21 days post-treatment with albendazole, moxidectin, or pyrantel, yielded mean FEC of 1874, 335, and 600 EPG, respectively. Samples collected >21 days post-treatment with albendazole or moxidectin yielded mean FEC of 1819 and 1117 EPG, respectively. We obtained DNA from hookworm eggs isolated from 70 fecal samples, comprised of 60 individual dogs and 10 pools from multiple dogs. Deep sequencing of the isotype 1 β-tubulin gene revealed the presence of the F167Y (TTC>TAC) resistance polymorphism in 99% of these samples, with 69% having ≥75% resistant allele frequency. No resistance-associated polymorphisms were seen at any of the other β-tubulin codons previously reported as associated with benzimidazole resistance in Strongylid nematodes. These clinical,in vitro, and genetic data provide strong evidence that racing and recently retired greyhound dogs in the USA are infected with MDRA. caninumat very high levels in terms of both prevalence and infection intensity.
Diet Potentially Drives the Differentiation of Eating Behaviours via Alterations to the Gut Microbiome in Infants
Authors: Yan Cathy , Zhao Helen , Nayar Navika , Rhee Kyung E. , Lumeng Julie C.
Published: April 2021

Certain infant eating behaviours are associated with adverse health outcomes such as obesity. While a diet consisting of infant formula has been linked to higher-risk eating behaviours and changes in the gut microbiome, little is known about what role the gut microbiome plays in mediating eating behaviours. Using 16S rRNA sequences extracted from 96 fecal samples collected from 58 infants, we identified a subset of bacterial taxa that were more abundant in formula-fed infants, primarily composed of the phylum Firmicutes. The presence of these taxa correlated with a lower drive to eat (i.e., lower food responsiveness). Furthermore, short-chain fatty acid production pathways were significantly more abundant in formula-fed infants, negatively correlated with food responsiveness, and positively associated with relative abundance of the Firmicutes subset. Our results suggest that higher abundances of Firmicutes in formula-fed infants may decrease their food responsiveness through short-chain fatty acid production in the first four months of life. Taken together, these findings suggest a potential role for the infant’s diet in impacting eating behaviour via changes to the gut microbiome, which may lead to the development of novel interventions for the prevention of childhood obesity.
Transcriptional activation of Il36A by C/EBPβ via a half-CRE•C/EBP element in murine macrophages is independent of its CpG methylation level
Authors: Nerlich Andreas , Janze Nina , Goethe Ralph
Published: April 2021

Interleukin-36α (Il-36α) is a member of the novel Il-1-like proinflammatory cytokine family that is highly expressed in epithelial tissues and several myeloid-derived cell types. We have recently shown that CCAAT enhancer binding protein β (C/EBPβ) binds specifically to an essential half cAMP response element (half-CRE)•C/EBP motif in the Il36A promoter to induce Il36A expression upon LPS stimulation. C/EBPs are transcription factors belonging to the basic leucine zipper (bZIP) family of transcriptional regulators. C/EBP proteins can form homo- and heterodimers and regulate gene expression by binding to C/EBP specific recognition sequences and composite sites that can contain 5′-cytosine-phosphate-guanine-3′ dinucleotides (CpG). CpG methylation of such elements has been shown to influence transcription factor binding and gene expression. Here we show that the half-CRE•C/EBP element in the Il36A promoter is differentially methylated in the murine RAW264.7 macrophage cell line and in primary murine macrophages. By using electrophoretic mobility gel shift and fluorescence polarization assays we demonstrate that C/EBPβ binding to the half-CRE•C/EBP element in the Il36A promoter following LPS stimulation is insensitive to CpG methylation. Transfection assays also show that methylation of the CpG in the half-CRE•C/EBP element does not alter LPS-induced Il36A promoter activity. A direct comparison of Il36A mRNA copy numbers as well as the pro-Il-36α protein level in RAW264.7 and primary macrophages revealed similar amounts in both cell types. Taken together, our data suggest that C/EBPβ binding to the half-CRE•C/EBP element and C/EBPβ mediated gene activation occurs independently of the CpG methylation status of the target DNA sequence and underline the potential of C/EBPβ to recognize methylated as well as unmethylated binding sites.