bluuebunny/crossref_metadata_2025 huggingface dataset:
Extreme diet without calcium may lead to hyperoxaluria and kidney stone recurrence—A case study
Authors: Šálek Tomáš
Published: August 2020

Background

The aim of the study was to present a case study of a 56‐year‐old woman with hyperoxaluria induced by calcium‐free diet that resulted in kidney stone recurrence.

Methods

A 24‐hour urine collection and serum tests for kidney stone risk factors identification were performed. The monitoring of urine risk factors was done by untimed urine samples and 24‐hour urine collections. Polarized light microscopy was performed for kidney stone analysis.

Results

The results of urine collection showed hyperoxaluria of 0.551 mmoL per 24 hours. After adding calcium‐containing products to the diet the oxaluria decreased to reference range value of 0.352 mmoL/24 hours and all untimed oxalate to creatinine ratios returned to reference ranges. Polarized light microscopy revealed 100% calcium oxalate kidney stone composition (It was 50% Weddellite and 50% Whewellite).

Conclusions

The case study shows the importance of calcium intake in the prevention of calcium oxalate kidney stone recurrence. Particularly, unsuitable diet without calcium can induce kidney stone recurrence. Knowledge of diet habits is important for interpretation of kidney stone risk factors and their inhibitors excreted in urine.
Quantification of aromatase binding in the female human brain using [11C]cetrozole positron emission tomography
Authors: Jonasson My , Nordeman Patrik , Eriksson Jonas , Wilking Helena , Wikström Johan , Takahashi Kayo , Niwa Takashi , Hosoya Takamitsu , Watanabe Yasuyoshi , Antoni Gunnar , Sundström Poromaa Inger , Lubberink Mark , Comasco Erika
Published: August 2020

Aromatase, the enzyme that in the brain converts testosterone and androstenedione to estradiol and estrone, respectively, is a putative key factor in psychoneuroendocrinology. In vivo assessment of aromatase was performed to evaluate tracer kinetic models and optimal scan duration, for quantitative analysis of the aromatase positron emission tomography (PET) ligand [11C]cetrozole. Anatomical magnetic resonance and 90‐min dynamic [11C]cetrozole PET‐CT scans were performed on healthy women. Volume of interest (VOI)‐based analyses with a plasma‐input function were performed using the single‐tissue and two‐tissue (2TCM) reversible compartment models and plasma‐input Logan analysis. Additionally, the simplified reference tissue model (SRTM), Logan reference tissue model (LRTM), and standardized uptake volume ratio model, with cerebellum as reference region, were evaluated. Parametric images were generated and regionally averaged voxel values were compared with VOI‐based analyses of the reference tissue models. The optimal reference model was used for evaluation of a decreased scan duration. Differences between the plasma‐input‐ and reference tissue‐based methods and comparisons between scan durations were assessed by linear regression. The [11C]cetrozole time–activity curves were best described by the 2TCM. SRTM nondisplaceable binding potential (BPND), with cerebellum as reference region, can be used to estimate [11C]cetrozole binding and generated robust and quantitatively accurate results for a reduced scan duration of 60 min. Receptor parametric mapping, a basis function implementation of SRTM, as well as LRTM, produced quantitatively accurate parametric images, showing BPND at the voxel level. As PET tracer, [11C]cetrozole can be employed for relatively short brain scans to measure aromatase binding using a reference tissue‐based approach.
Gravimetric quantitative validation of botanic impurities in feed
Authors: Marchis Daniela , Amato Giuseppina , Giovannini Tiziana , Khadjavi Amina , Morello Sara , Gili Marilena , Pinotti Luciano , Vrhovnik Igor Ujčič
Published: August 2020

Background

Harmful botanical impurities may contaminate feed and feed materials and be a potential danger to animal or human health, or to the environment. The aim of this study was to establish rapid and sensitive methods that can be used in routine official controls to determine botanical impurities such as Datura stramonium, Ricinus communis, Crotaliaria spp., and Ambrosia spp. in animal feed and raw materials. Claviceps sclerotia were also detected in cereals, due to the similarities of the targets and the analytical procedure. Regulation (EU) 625/2017, which replaces Reg. 2004/882/EC, states that EU member states should conduct official controls in assessed and accredited laboratories and that the analytical methods must be validated before use by considering parameters such as specificity, precision, recovery, and measurement uncertainly.

Results and Conclusion

The results demonstrate that all of the methods tested are suitable for the official quantitative analyses required by EU official legislation. © 2020 Society of Chemical Industry
Regulatory T cells: A potential weapon to combat COVID‐19?
Authors: Liu Yu , Qi Guangying , Bellanti Joseph A. , Moser René , Ryffel Bernhard , Zheng Song Guo
Published: August 2020

Since the end of December 2019, a novel coronavirus SARS‐CoV‐2 began to spread, an infection disease termed COVID‐19. The virus has spread throughout the world in a short period of time, resulting in a pandemic. The number of reported cases in global reached 5 695 596 including 352 460 deaths, as of May 27, 2020. Due to the lack of effective treatment options for COVID‐19, various strategies are being tested. Recently, pathologic studies conducted by two teams in China revealed immunopathologic abnormalities in lung tissue. These results have implications for immunotherapy that could offer a novel therapy strategy for combating lethal viral pneumonia. This review discusses the clinical and pathological features of COVID‐19, the roles of immune cells in pathological processes, and the possible avenues for induction of immunosuppressive T regulatory cells attenuating lung inflammation due to viral infection. It is our hope that these proposals may both be helpful in understanding the novel features of SARS‐CoV‐2 pneumonia as well as providing new immunological strategies for treating the severe sequelae of disease manifestations seen in people infected with SARS‐CoV‐2.
Inverse source problem for a diffusion equation involving the fractional spectral Laplacian
Authors: BenSalah Mohamed , Hassine Maatoug
Published: August 2020

In this paper, we consider an inverse problem related to a fractional diffusion equation. The model problem is governed by a nonlinear partial differential equation involving the fractional spectral Laplacian. This study is focused on the reconstruction of an unknown source term from a partial internal measured data. The considered ill‐posed inverse problem is formulated as a minimization one. The existence, uniqueness, and stability of the solution are discussed. Some theoretical results are established. The numerical reconstruction of the unknown source term is investigated using an iterative process. The proposed method involves a denoising procedure at each iteration step and provides a sequence of source term approximations converging in norm to the actual solution of the minimization problem. Some numerical results are presented to show the efficiency and the accuracy of the proposed approach.
Human mesenchymal stromal cells and derived extracellular vesicles: Translational strategies to increase their proangiogenic potential for the treatment of cardiovascular disease
Authors: Nazari-Shafti Timo Z. , Neuber Sebastian , Garcia Duran Ana , Xu Zhiyi , Beltsios Eleftherios , Seifert Martina , Falk Volkmar , Stamm Christof
Published: August 2020

Mesenchymal stromal cells (MSCs) offer great potential for the treatment of cardiovascular diseases (CVDs) such as myocardial infarction and heart failure. Studies have revealed that the efficacy of MSCs is mainly attributed to their capacity to secrete numerous trophic factors that promote angiogenesis, inhibit apoptosis, and modulate the immune response. There is growing evidence that MSC-derived extracellular vesicles (EVs) containing a cargo of lipids, proteins, metabolites, and RNAs play a key role in this paracrine mechanism. In particular, encapsulated microRNAs have been identified as important positive regulators of angiogenesis in pathological settings of insufficient blood supply to the heart, thus opening a new path for the treatment of CVD. In the present review, we discuss the current knowledge related to the proangiogenic potential of MSCs and MSC-derived EVs as well as methods to enhance their biological activities for improved cardiac tissue repair. Increasing our understanding of mechanisms supporting angiogenesis will help optimize future approaches to CVD intervention.

Significance statement Mesenchymal stromal cells (MSCs) are currently being evaluated in clinical trials for the treatment of numerous diseases. Their therapeutic potential is mainly due to the factors they secrete. Studies have demonstrated that MSCs also produce extracellular vesicles that carry proteins, metabolites, lipids, and various RNAs. Based on their multifunctional properties, extracelullar vesicles are of great importance and interest in the development of future medicine. This study provides an overview of the current knowledge on the therapeutic potential of MSCs and MSC-derived extracelullar vesicles, as well as methods for improving their biological activities to promote angiogenesis and tissue repair.
Triple‐Mode Emissions with Invisible Near‐Infrared After‐Glow from Cr3+‐Doped Zinc Aluminum Germanium Nanoparticles for Advanced Anti‐Counterfeiting Applications
Authors: Zhang Yi , Huang Rui , Li Hongliang , Lin Zhenxu , Hou Dejian , Guo Yanqing , Song Jie , Song Chao , Lin Zewen , Zhang Wenxing , Wang Jing , Chu Paul K. , Zhu Chao
Published: August 2020

Materials exhibiting persistent luminescence (PersL) have great prospect in optoelectronic and biomedical applications such as optical information storage, bio‐imaging, and so on. Unfortunately, PersL materials with multimode emission properties have been rarely reported, although they are expected to be very desirable in multilevel anti‐counterfeiting and encryption applications. Herein, Cr3+‐doped zinc aluminum germanium (ZAG:Cr) nanoparticles exhibiting triple‐mode emissions are designed and demonstrated. Upon exposure to steady 254 nm UV light, the ZAG:Cr nanoparticles yield steady bluish‐white emission. After turning off the UV light, the emission disappears quickly and the mode switches to transient near‐infrared (NIR) PersL emission at predominantly 690 nm. The transient NIR PersL emission which arises from Cr3+ is induced by non‐equivalent substitution of Ge4+. After persisting for 50 min, it can be retriggered by 980 nm photons due to the continuous trap depth distribution of ZAG:Cr between 0.65 and 1.07 eV. Inspired by the triple‐mode emissions from ZAG:Cr, multifunctional luminescent inks composed of ZAG:Cr nanoparticles are prepared, and high‐security labeling and encoding encryption properties are demonstrated. The results indicate that ZAG:Cr nanoparticles have great potential in anti‐counterfeiting and encryption applications, and the strategy and concept described here provide insights into the design of advanced anti‐counterfeiting materials.
Partnering Small Enterprises and Local Nonprofits to Help Sustain Local Economies and Reduce the Spread of COVID‐19
Authors: Donahue Patricia Farrell
Published: August 2020

A lesson learned from decades of research is that businesses and nonprofits can form private partnerships to serve the public good. One such partnership is a cause‐related marketing campaign, where a business donates a portion of its sales to a nonprofit to address a social need. To help counter the devastating health and economic impact of COVID‐19, this article briefly describes how small enterprise and nonprofit partnerships might implement local cause‐related marketing campaigns focused on sustaining economic activity and slowing the spread of the pandemic. Successful campaigns may also enhance community self‐reliance and reduce health inequities. Public policies and programs could encourage these private partnerships.
Inhibition of Bruton’s tyrosine kinase interferes with pathogenic B-cell development in inflammatory CNS demyelinating disease
Authors: Torke Sebastian , Pretzsch Roxanne , Häusler Darius , Haselmayer Philipp , Grenningloh Roland , Boschert Ursula , Brück Wolfgang , Weber Martin S.
Published: August 2020

Anti-CD20-mediated B-cell depletion effectively reduces acute multiple sclerosis (MS) flares. Recent data shows that antibody-mediated extinction of B cells as a lasting immune suppression, harbors the risk of developing humoral deficiencies over time. Accordingly, more selective, durable and reversible B-cell-directed MS therapies are needed. We here tested inhibition of Bruton’s tyrosine kinase (BTK), an enzyme centrally involved in B-cell receptor signaling, as the most promising approach in this direction. Using mouse models of MS, we determined that evobrutinib, the first BTK inhibiting molecule being developed, dose-dependently inhibited antigen-triggered activation and maturation of B cells as well as their release of pro-inflammatory cytokines. Most importantly, evobrutinib treatment functionally impaired the capacity of B cells to act as antigen-presenting cells for the development of encephalitogenic T cells, resulting in a significantly reduced disease severity in mice. In contrast to anti-CD20, BTK inhibition silenced this key property of B cells in MS without impairing their frequency or functional integrity. In conjunction with a recent phase II trial reporting that evobrutinib is safe and effective in MS, our mechanistic data highlight therapeutic BTK inhibition as a landmark towards selectively interfering with MS-driving B-cell properties.
The impact of tree crops and temperature on the timing of frugivorous bird migration
Authors: Kanerva Anna-Maria , Hokkanen Tatu , Lehikoinen Aleksi , Norrdahl Kai , Suhonen Jukka
Published: August 2020

Migration has evolved to tackle temporal changes in availability of resources. Climate change has been shown to affect the migration dates of species, which raises the question of whether the variation in the timing of migration is climate or resource dependent? The relative importance of temperature and availability of food as drivers of migration behaviour during both spring and autumn seasons has been poorly studied. Here, we investigated these patterns in frugivorous and granivorous birds (hereafter frugivorous) that are assumed to postpone their autumn migration when there is plenty of food available, which may also advance upcoming spring migration. On the other hand, especially spring migration dates have been negatively connected with increasing temperatures. We tested whether the autumn and spring migration dates of eleven common frugivorous birds depended on the crop size of trees or ambient temperatures using 29 years of data in Finland. The increased crop sizes of trees delayed autumn migration dates; whereas, autumn temperature did not show a significant connection. We also observed a temporal trend towards later departure. Increasing temperature and crop sizes advanced spring arrival dates. Our results support the hypothesis that the timing of autumn migration in the frugivorous birds depends on the availability of food and is weakly connected with the variation in temperature. Importantly, crop size can have carry-over effects and affect the timing of spring arrival possibly because birds have overwintered closer to the breeding grounds after an abundant crop year.
Transfer effects of mathematical literacy: an integrative longitudinal study
Authors: Holenstein Mathias , Bruckmaier Georg , Grob Alexander
Published: August 2020

Mathematical literacy (ML) is considered central to the application of mathematical knowledge in everyday life and thus is found in many comparative international educational standards. However, there exists barely any evidence about predictors and outcomes of ML having a lasting effect on achievement in nonmathematical domains. We drew on a large longitudinal sample of N = 4001 secondary school students in Grades 5 to 9 and tested for effects of ML on later academic achievement. We took prior achievement in different domains (information and communication technology literacy, scientific literacy, reading comprehension, and listening comprehension), socioeconomic status, and gender into account and investigated predictive effects of math grade, mathematical self-concept, reasoning, and prior achievement on ML. Using structural equation models, we found support for the importance of integrating multiple predictors and revealed a transfer effect of ML on achievement in different school domains. The findings highlight the importance of ML for school curricula and lasting educational decisions.
Forming COVID-19 Policy Under Uncertainty
Authors: Manski Charles F.
Published: August 2020

This paper presents my thinking and concerns about formation of COVID-19 policy. Policy formation must cope with substantial uncertainties about the nature of the disease, the dynamics of transmission, and behavioral responses. Data uncertainties limit our knowledge of the past trajectory and current state of the pandemic. Data and modeling uncertainties limit our ability to predict the impacts of alternative policies. I explain why current epidemiological and macroeconomic modeling cannot deliver realistically optimal policy. I describe my recent work quantifying basic data uncertainties that make policy analysis difficult. I discuss approaches for policy choice under uncertainty and suggest adaptive policy diversification.
A Note on the Decomposition of Aerodynamic Forces Induced by A Wind Turbine Flaps
Authors: Niu Y. Y. , Shih P. J. , Kong S. C.
Published: August 2020

In this study, the aerodynamic characteristics of a vertical-axis wind turbine blade coupled with a high-lift device, such as the Gurney flap at the trailing edge, are investigated. For numerical analysis, the force element theory is used to understand how the Gurney flap influences the force evolution of the lift-type vertical-axis wind turbine. This study shows that the lift and drag can be respectively approximated into four elements, which are induced by volume vorticity, rotational velocity, angular acceleration and surface friction of the flow around the blades. Based on the perspective of the force element theory, the present simulation provides a clear picture of how the Gurney flap influences the formation of the aerodynamic force elements during a rotational cycle for a vertical-axis wind turbine. Simulation results show that the contributions mainly result from the surface vorticities, the rotational acceleration of the airfoil, and the acceleration of the surface.
Back to basics
Authors: Zhou Xiaozhou (Emily) , Zha Mingjian
Published: August 2020

The English major programme and related academic disciplines in Chinese universities are apparently experiencing growing pains as documented in the article entitled ‘The English Major Crisis in China’ published in this journal (Chen, 2019). In the article, Chen analysed the controversies surrounding the English major programme in Chinese universities and presented a somewhat gloomy prospect for the English major programme as an undergraduate subject in Chinese universities. Yet we found that the disheartening picture of the English major programme as portrayed by the article is open to question. We are also concerned that the article may misguide readers and negate the efforts that educators have undertaken to refine the English major programme in Chinese universities. For this reason, we would like to respond to the article with a different view, which has been made possible by our concerted efforts to bring the English major programme back to its basics over the last few years. We argue that the English major programme will play a critical role in promoting humanistic education in Chinese universities.
Global Leadership in Paediatric and Congenital Cardiac Care: “Following the ‘Golden Rule’ in multicentre collaborations – an interview with Jane W. Newburger, MD”
Authors: Tretter Justin T. , Jacobs Jeffrey P.
Published: August 2020

Dr. Jane Newburger is the focus of our first in a planned series of interviews inCardiology in the Youngentitled, “Global Leadership in Paediatric and Congenital Cardiac Care”. Dr. Newburger was born in Manhattan, New York, United States of America. She was raised in the Bronx for her first six years of life, at which point her family moved to Yonkers, New York, where she spent the rest of her childhood. She then attended Bryn Mawr College where she majored in psychology. Dr. Newburger subsequently attended Harvard Medical School, graduating in 1974. She did her internship and residency in paediatrics at Boston Children’s Hospital in 1974–1976, followed by her fellowship at Boston Children’s Hospital in 1976–1979. She received her Masters in Public Health at the Harvard School of Public Health in 1980.

Dr. Newburger has spent her entire career as a paediatric cardiologist at Boston Children’s Hospital and Harvard Medical School, where she was appointed a Professor of Pediatrics in 1999 and has held the position as Commonwealth Professor of Pediatrics since 2008. She has established herself as a leading clinical scientist within the field of paediatric cardiology, with expertise in leadership of multicentre and multidisciplinary research, including the building of collaborative groups. She has been continuously funded by the National Institute of Health since 1982, and amongst other areas has led the field in the areas of neurodevelopmental outcomes in congenital heart disease, improved methods of vital organ support, and management of Kawasaki disease. This article presents our interview with Dr. Newburger, an interview that covers her path towards becoming a clinical scientist, her interests spanning four decades of hard work, and her strategies to design and lead successful multicentre studies.
Hidden welfare effects of tree plantations
Authors: Anríquez Nilson Gustavo , Toledo Roman Gabriela , Arriagada Cisternas Rodrigo
Published: August 2020

Subsidies to promote tree plantations have been questioned because of negative impacts of the forestry industry. Quantitative evidence on the socioeconomic impacts of afforestation subsidies or of tree plantations is elusive, mainly due to data scarcity. We assess the overall impact of a tree plantation subsidy in Chile, using our original 20-year panel dataset that includes small area estimates of poverty and the subsidy assignment at the census-district scale. We show that forestry subsidies – on average – in fact, do increase poverty. More specifically, using difference in difference with matching techniques, and instrumental variables approaches, we show that there is an increase of about 2 per cent in the poverty rate of treated localities. We identify employment as a causal mechanism explaining this finding, since we found a negative effect of tree plantations on employment, and therefore, on poverty. We suggest reassessment of the distributional effects of the forest subsidy and forestry industry.
Reduction of SCUBE3 by a new marine-derived asterosaponin leads to arrest of glioma cells in G1/S
Authors: Qiu Peng-Cheng , Lu Yun-Yang , Zhang Shan , Li Hua , Bao Han , Ji Yu-Qiang , Fang Fei , Tang Hai-Feng , Cheng Guang
Published: August 2020

Many saponins are characterized as exhibiting a wide spectrum of antitumor activities at low concentrations. Most of the previous studies that aimed to understand the mechanisms underlying anticancer saponins have focused on numerous classical signaling pathways. However, at the oncogene level, little is known about the action of saponins, especially asterosaponin. In this study, CN-3, a new asterosaponin isolated from the starfish Culcita novaeguineae, decreased the proliferation of U87 and U251 cells at low doses in a dose- and time-dependent manner. Microarray analysis revealed CN-3 significantly induced the differential expression of 661 genes that are related to its antiglioma effect in U251. Nine downregulated genes (SCUBE3, PSD4, PGM2L1, ACSL3, PRICKLE1, ABI3BP, STON1, EDIL3, and KCTD12) were selected, for further verification of their low expression. Then, shRNA transfection and high-content screening were performed and significantly decreased U251 cell proliferation rate was only observed for the SCUBE3 knockdown. qPCR confirmed SCUBE3 was highly expressed in U251 and U87 cells, and had medium expression levels in U373 cells. Real-time cellular analysis using iCELLigence demonstrated that SCUBE3 is an oncogene in U251 and U87 cells, with knockdown of SCUBE3 inhibiting U251 and U87 cell proliferation while, conversely, SCUBE3 overexpression promoted their proliferation. Afterward, SCUBE3 protein was found to have high expression in primary glioma specimens from patients examined by immunohistochemistry but low expression in normal brain. PathScan ELISA analysis in conjunction with TEM observation demonstrated that the effect of SCUBE3 knockdown in U251 does not appear to be related to the induction of apoptosis. Employing CCK-8, iCELLigence, flow cytometry, western blotting, and shRNA transfection (knockdown and overexpression) experiments, we reveal that the reduction of SCUBE3 expression, induced by CN-3, mediated both inhibition and G1/S arrest of U251 via the Akt/p-Akt/p53/p21/p27/E2F1 pathway.
Expression of green fluorescent protein defines a specific population of lamina II excitatory interneurons in the GRP::eGFP mouse
Authors: Bell Andrew M. , Gutierrez-Mecinas Maria , Stevenson Anna , Casas-Benito Adrian , Wildner Hendrik , West Steven J. , Watanabe Masahiko , Todd Andrew J.
Published: August 2020

Dorsal horn excitatory interneurons that express gastrin-releasing peptide (GRP) are part of the circuit for pruritogen-evoked itch. They have been extensively studied in a transgenic line in which enhanced green fluorescent protein (eGFP) is expressed under control of the Grp gene. The GRP-eGFP cells are separate from several other neurochemically-defined excitatory interneuron populations, and correspond to a class previously defined as transient central cells. However, mRNA for GRP is widely distributed among excitatory interneurons in superficial dorsal horn. Here we show that although Grp mRNA is present in several transcriptomically-defined populations, eGFP is restricted to a discrete subset of cells in the GRP::eGFP mouse, some of which express the neuromedin receptor 2 and likely belong to a cluster defined as Glut8. We show that these cells receive much of their excitatory synaptic input from MrgA3/MrgD-expressing nociceptive/pruritoceptive afferents and C-low threshold mechanoreceptors. Although the cells were not innervated by pruritoceptors expressing brain natriuretic peptide (BNP) most of them contained mRNA for NPR1, the receptor for BNP. In contrast, these cells received only ~ 10% of their excitatory input from other interneurons. These findings demonstrate that the GRP-eGFP cells constitute a discrete population of excitatory interneurons with a characteristic pattern of synaptic input.
Human Chagas-Flow ATE-IgG1 for advanced universal and Trypanosoma cruzi Discrete Typing Units-specific serodiagnosis of Chagas disease
Authors: Alessio Glaucia Diniz , de Araújo Fernanda Fortes , Silva Jéssica Spínola , Júnior Policarpo Ademar Sales , de Souza Gomes Matheus , do Amaral Laurence Rodrigues , Ramírez Juan David , Flórez Carolina , Teixeira-Carvalho Andréa , de Barros Pinheiro Melina , de Lana Marta , Martins-Filho Olindo Assis
Published: August 2020

The molecular and serological methods available for Discrete Typing Units (DTU)-specific diagnosis of Trypanosoma cruzi in chronic Chagas disease present limitations. The study evaluated the performance of Human Chagas-Flow ATE-IgG1 for universal and DTU-specific diagnosis of Chagas disease. A total of 102 sera from Chagas disease patients (CH) chronically infected with TcI, TcVI or TcII DTUs were tested for IgG1 reactivity to amastigote/(A), trypomastigote/(T) and epimastigote/(E) antigens along the titration curve (1:250–1:32,000). The results demonstrated that “AI 250/40%”, “EVI 250/30%”, “AII 250/40%”, “TII 250/40%” and “EII 250/30%” have outstanding accuracy (100%) to segregate CH from non-infected controls. The attributes “TI 4,000/50%”, “EI 2,000/50%”, “AVI 8,000/60%” and “TVI 4,000/50%” were selected for DTU-specific serotyping of Chagas disease. The isolated use of “EI 2,000/50%” provided the highest co-positivity for TcI patients (91%). The combined decision tree algorithms using the pre-defined sets of attributes showed outstanding full accuracy (92% and 97%) to discriminate “TcI vs TcVI vs TcII” and “TcI vs TcII” prototypes, respectively. The elevated performance of Human Chagas-Flow ATE-IgG1 qualifies its use for universal and TcI/TcVI/TcII-specific diagnosis of Chagas disease. These findings further support the application of this method in epidemiological surveys, post-therapeutic monitoring and clinical outcome follow-ups for Chagas disease.
Comparative assessment of genetic diversity matrices and clustering methods in white Guinea yam (Dioscorea rotundata) based on morphological and molecular markers
Authors: Darkwa Kwabena , Agre Paterne , Olasanmi Bunmi , Iseki Kohtaro , Matsumoto Ryo , Powell Adrian , Bauchet Guillaume , De Koeyer David , Muranaka Satoru , Adebola Patrick , Asiedu Robert , Terauchi Ryohei , Asfaw Asrat
Published: August 2020

Understanding the diversity and genetic relationships among and within crop germplasm is invaluable for genetic improvement. This study assessed genetic diversity in a panel of 173D. rotundataaccessions using joint analysis for 23 morphological traits and 136,429 SNP markers from the whole-genome resequencing platform. Various diversity matrices and clustering methods were evaluated for a comprehensive characterization of genetic diversity in white Guinea yam from West Africa at phenotypic and molecular levels. The translation of the different diversity matrices from the phenotypic and genomic information into distinct groups varied with the hierarchal clustering methods used. Gower distance matrix based on phenotypic data and identity by state (IBS) distance matrix based on SNP data with the UPGMA clustering method found the best fit to dissect the genetic relationship in current set materials. However, the grouping pattern was inconsistent (r = − 0.05) between the morphological and molecular distance matrices due to the non-overlapping information between the two data types. Joint analysis for the phenotypic and molecular information maximized a comprehensive estimate of the actual diversity in the evaluated materials. The results from our study provide valuable insights for measuring quantitative genetic variability for breeding and genetic studies in yam and other root and tuber crops.
Faster visual reaction times in elite athletes are not linked to better gaze stability
Authors: Barrett Brendan T. , Cruickshank Alice G. , Flavell Jonathan C. , Bennett Simon J. , Buckley John G. , Harris Julie M. , Scally Andrew J.
Published: August 2020

The issue of whether visually-mediated, simple reaction time (VRT) is faster in elite athletes is contentious. Here, we examined if and how VRT is affected by gaze stability in groups of international cricketers (16 females, 28 males), professional rugby-league players (21 males), and non-sporting controls (20 females, 30 males). VRT was recorded via a button-press response to the sudden appearance of a stimulus (circular target—diameter 0.8°), that was presented centrally, or 7.5° to the left or right of fixation. The incidence and timing of saccades and blinks occurring from 450 ms before stimulus onset to 225 ms after onset were measured to quantify gaze stability. Our results show that (1) cricketers have faster VRT than controls; (2) blinks and, in particular, saccades are associated with slower VRT regardless of the level of sporting ability; (3) elite female cricketers had steadier gaze (fewer saccades and blinks) compared to female controls; (4) when we accounted for the presence of blinks and saccades, our group comparisons of VRT were virtually unchanged. The stability of gaze is not a factor that explains the difference between elite and control groups in VRT. Thus we conclude that better gaze stability cannot explain faster VRT in elite sports players.
Correlation between hemolytic activity, cytotoxicity and systemic in vivo toxicity of synthetic antimicrobial peptides
Authors: Greco Ines , Molchanova Natalia , Holmedal Elin , Jenssen Håvard , Hummel Bernard D. , Watts Jeffrey L. , Håkansson Joakim , Hansen Paul R. , Svenson Johan
Published: August 2020

The use of non-standard toxicity models is a hurdle in the early development of antimicrobial peptides towards clinical applications. Herein we report an extensive in vitro and in vivo toxicity study of a library of 24 peptide-based antimicrobials with narrow spectrum activity towards veterinary pathogens. The haemolytic activity of the compounds was evaluated against four different species and the relative sensitivity against the compounds was highest for canine erythrocytes, intermediate for rat and human cells and lowest for bovine cells. Selected peptides were additionally evaluated against HeLa, HaCaT and HepG2 cells which showed increased stability towards the peptides. Therapeutic indexes of 50–500 suggest significant cellular selectivity in comparison to bacterial cells. Three peptides were administered to rats in intravenous acute dose toxicity studies up to 2–8 × MIC. None of the injected compounds induced any systemic toxic effects in vivo at the concentrations employed illustrating that the correlation between the different assays is not obvious. This work sheds light on the in vitro and in vivo toxicity of this class of promising compounds and provides insights into the relationship between the different toxicity models often employed in different manners to evaluate the toxicity of novel bioactive compounds in general.
Automated and rapid self-report of nociception in transgenic mice
Authors: Black Christopher J. , Allawala Anusha B. , Bloye Kiernan , Vanent Kevin N. , Edhi Muhammad M. , Saab Carl Y. , Borton David A.
Published: August 2020

There are currently no rapid, operant pain behaviors in rodents that use a self-report to directly engage higher-order brain circuitry. We have developed a pain detection assay consisting of a lick behavior in response to optogenetic activation of predominantly nociceptive peripheral afferent nerve fibers in head-restrained transgenic mice expressing ChR2 in TRPV1 containing neurons. TRPV1-ChR2-EYFP mice (n = 5) were trained to provide lick reports to the detection of light-evoked nociceptive stimulation to the hind paw. Using simultaneous video recording, we demonstrate that the learned lick behavior may prove more pertinent in investigating brain driven pain processes than the reflex behavior. Within sessions, the response bias of transgenic mice changed with respect to lick behavior but not reflex behavior. Furthermore, response similarity between the lick and reflex behaviors diverged near perceptual threshold. Our nociceptive lick-report detection assay will enable a host of investigations into the millisecond, single cell, neural dynamics underlying pain processing in the central nervous system of awake behaving animals.
Asynchrony among insect pollinator groups and flowering plants with elevation
Authors: Adedoja Opeyemi , Kehinde Temitope , Samways Michael J.
Published: August 2020

Mountains influence species distribution through differing climate variables associated with increasing elevation. These factors determine species niche ranges and phenology. Although the distribution patterns of some specific insect groups relative to elevation have been determined, how differing environmental conditions across elevation zones differentially influence the phenology of various insect groups is largely unknown. This is important in this era of rapid climate change. We assess here how species composition and seasonal peaks in abundance among different insect pollinator groups and flowering plants differ across four floristically distinct elevation zones up a sentinel mountain subject to strong weather events. We sampled insect pollinators in four major groups (bees, wasps, beetles and flies) over two spring seasons. Pollinator species composition across all elevation zones tracks flowering plant species composition. In terms of abundance, beetles were the dominant group across the three lower zones, but declined greatly in the summit zone, where flies and bees were more abundant. Bee abundance peaked earlier than the other groups across all four elevation zones, where there were significant peaks in abundance. Bee abundance peaked earlier than flowering plants at the middle zone and slightly later than flowering plants at the base zone, suggesting a mismatch. We conclude that, while elevation shapes species distribution, it also differentially influences species phenology. This may be of great significance in long-term assessment of species distribution in sensitive mountain ecosystems.
RNA polymerase II subunit D is essential for zebrafish development
Authors: Maeta Masanari , Kataoka Miku , Nishiya Yusuke , Ogino Kazutoyo , Kashima Makoto , Hirata Hiromi
Published: August 2020

DNA-directed RNA polymerase II (pol II) is composed of ten core and two dissociable subunits. The dissociable subcomplex is a heterodimer of Rpb4/Polr2d and Rpb7/Polr2g, which are encoded by RPB4/polr2d and RPB7/polr2g genes, respectively. Functional studies of Rpb4/Polr2d in yeast have revealed that Rpb4 plays a role primarily in pol II-mediated RNA synthesis and partly in various mRNA regulations including pre-mRNA splicing, nuclear export of mRNAs and decay of mRNAs. Although Rpb4 is evolutionally highly conserved from yeast to human, it is dispensable for survival in budding yeast S. cerevisiae, whereas it was indispensable for survival in fission yeast S. pombe, slime molds and fruit fly. To elucidate whether Rpb4/Polr2d is necessary for development and survival of vertebrate animals, we generated polr2d-deficient zebrafish. The polr2d mutant embryos exhibited progressive delay of somitogenesis at the onset of 11 h postfertilization (hpf). Mutant embryos then showed increased cell death at 15 hpf, displayed hypoplasia such as small eye and cardiac edema by 48 hpf and prematurely died by 60 hpf. In accordance with these developmental defects, our RT-qPCR revealed that expression of housekeeping and zygotic genes was diminished in mutants. Collectively, we conclude that Rpb4/Polr2d is indispensable for vertebrate development.
Entry of Panton–Valentine leukocidin-positive methicillin-resistant Staphylococcus aureus into the hospital: prevalence and population structure in Heidelberg, Germany 2015–2018
Authors: Klein Sabrina , Hannesen Julius , Zanger Philipp , Heeg Klaus , Boutin Sébastien , Nurjadi Dennis
Published: August 2020

Staphylococcus aureus is one of the major pathogens causing community—and healthcare-acquired infections. The presence of the virulence factor Panton–Valentine leukocidin (PVL) is associated with recurrent infection and clinical severity and generally regarded as a feature of community associated-methicillin-resistant Staphylococcus aureus (MRSA). To date, the focus of PVL-positive MRSA in hospitalized patients has been on outbreaks. We aimed to investigate whether PVL-positive MRSA has penetrated the community-hospital barrier by determining the prevalence of PVL in MRSA of hospitalized patients. MRSA strains isolated from patients hospitalized > 48 h in Heidelberg University Hospital between 2015 and 2018 Isolates were analysed for the presence of PVL and subjected to spa-typing. PVL-positive MRSA were then characterized by whole genome sequencing. We analysed 740 MRSA isolates in the study period and identified 6.2% (n = 46) PVL-positivity. 32.6% of PVL-positive MRSA met the criteria for nosocomial acquisition. The most frequent clones among the PVL-positive strains were ST80-t044 (21.7%, n = 10/46) and ST8-t008 (19.5%, n = 9/46). WGS identified three possible transmission clusters involving seven patients. In conclusion, we found successful epidemic PVL-positive MRSA clones entering the hospital and causing nosocomial infections. Preventive measures and constant surveillance should be maintained to prevent transmissions and clonal outbreaks.
Epidemiology of human papillomavirus-related oropharyngeal cancer in a classically low-burden region of southern Europe
Authors: Mena M. , Frias-Gomez J. , Taberna M. , Quirós B. , Marquez S. , Clavero O. , Baena A. , Lloveras B. , Alejo M. , León X. , García J. , Mesía R. , Bermejo O. , Bonfill T. , Aguila A. , Guix M. , Hijano R. , Pavón M. A. , Torres M. , Tous S. , Clèries R. , Alemany L.
Published: August 2020

The incidence of human papillomavirus (HPV)-related oropharyngeal cancer is increasing in some regions. Nevertheless, the epidemiology of this disease has not been extensively investigated in southern Europe. We conducted a retrospective cohort study of patients diagnosed with primary oropharyngeal cancer from 1991 to 2016. Cancer tissues underwent histopathological evaluation, DNA quality control, HPV-DNA detection and p16INK4aimmunohistochemistry. Data were collected from medical records. Factors associated with HPV positivity and time trends were evaluated with multivariable Bayesian models. The adjusted prevalence of HPV-related cases in 864 patients with a valid HPV-DNA result was 9.7%, with HPV-DNA/p16INK4adouble positivity being considered. HPV-related oropharyngeal cancer was likely to occur in non-smokers and non-drinkers, to be located in the tonsil or diagnosed at advanced stages. Time-trend analysis showed an increasing risk of HPV-related oropharyngeal cancer in the most recent periods (5-year period increase of 30%). This increase was highest and with a clear increasing trend only in the most recent years (2012–2016). The prevalence of HPV-related oropharyngeal cancer started to sharply increase in the most recent years in our setting, as occurred two decades ago in areas where most oropharyngeal cancer cases are currently HPV-related. Our results provide a comprehensive assessment of the epidemiological landscape of HPV-related oropharyngeal cancer in a region of southern Europe.
Manuka honey microneedles for enhanced wound healing and the prevention and/or treatment of Methicillin-resistant Staphylococcus aureus (MRSA) surgical site infection
Authors: Frydman Galit H. , Olaleye David , Annamalai Damodaran , Layne Kim , Yang Illina , Kaafarani Haytham M. A. , Fox James G.
Published: August 2020

Manuka honey (MH) is currently used as a wound treatment and suggested to be effective in Methicillin-resistantStaphylococcus aureus(MRSA) elimination. We sought to optimize the synthesis of MH microneedles (MHMs) while maintaining the MH therapeutic effects. MHMs were synthesized using multiple methods and evaluated with in vitro assays. MHMs demonstrated excellent bactericidal activity against MRSA at concentrations ≥ 10% of honey, with vacuum-prepared honey appearing to be the most bactericidal, killing bacterial concentrations as high as 8 × 107 CFU/mL. The wound-healing assay demonstrated that, at concentrations of 0.1%, while the cooked honey had incomplete wound closure, the vacuum-treated honey trended towards faster wound closure. In this study, we demonstrate that the method of MHM synthesis is crucial to maintaining MH properties. We optimized the synthesis of MHMs and demonstrated their potential utility in the treatment of MRSA infections as well as in wound healing. This is the first report of using MH as a substrate for the formation of dissolvable microneedles. This data supports the need for further exploration of this new approach in a wound-healing model and opens the door for the future use of MH as a component of microneedle scaffolds.
Timing for antioxidant-priming against rice seed ageing: optimal only in non-resistant stage
Authors: Xu Ling-xiang , Xin Xia , Yin Guang-kun , Zhou Ji , Zhou Yuan-chang , Lu Xin-xiong
Published: August 2020

Seed deterioration due to ageing strongly affects both germplasm preservation and agricultural production. Decelerating seed deterioration and boosting seed viability become increasingly urgent. The loss of seed viability is inevitable even under cold storage. For species with short-lived seed or for regions with poor preservation infrastructure where cold storage is not readily available, seed enhancement is more reliable to increase seed viability and longevity. Antioxidant priming as a way of seed enhancement usually improves seed germination. As for post-priming survival, however, significant uncertainty exists. The controversy lies particularly on seeds of high germination percentage (GP > 95%) whose viability is hardly improvable and the benefits of priming depend on prolonging seed longevity. Therefore, this study timed antioxidant priming to prolong the longevity of high-viability seeds under artificially accelerated ageing (AAA). Rice (Nipponbare) seeds (GP > 97%) under room-temperature-storage (RTS) for 6 months. were resistant to AAA first with little viability loss for a certain period, the resistant stage. This resistance gradually vanished without GP change, during a prolonged RTS period which was named the vulnerable stage. According to the results, although antioxidant priming severely curtailed the resistant stage for seeds with a long plateau in the survival curve, it decelerated viability loss for seeds in the vulnerable stage. In complement to seed storage, priming potentially retains high seed GP which would decrease without seed enhancement. To maximize the benefits of priming for high-GP seeds, two time points are advised as the start of a time window for priming: (1) just at the end of the resistant stage without notable viability loss, which is hard to grasp by GP monitoring; (2) slight but identifiable GP decline.
A model of the PI cycle reveals the regulating roles of lipid-binding proteins and pitfalls of using mosaic biological data
Authors: Mazet Francoise , Tindall Marcus J. , Gibbins Jonathan M. , Fry Michael J.
Published: August 2020

The phosphatidylinositol (PI) cycle is central to eukaryotic cell signaling. Its complexity, due to the number of reactions and lipid and inositol phosphate intermediates involved makes it difficult to analyze experimentally. Computational modelling approaches are seen as a way forward to elucidate complex biological regulatory mechanisms when this cannot be achieved solely through experimental approaches. Whilst mathematical modelling is well established in informing biological systems, many models are often informed by data sourced from multiple unrelated cell types (mosaic data) or from purified enzyme data. In this work, we develop a model of the PI cycle informed by experimental and omics data taken from a single cell type, namely platelets. We were able to make a number of predictions regarding the regulation of PI cycle enzymes, the importance of the number of receptors required for successful GPCR signaling and the importance of lipid- and protein-binding proteins in regulating second messenger outputs. We then consider how pathway behavior differs, when fully informed by data for HeLa cells and show that model predictions remain consistent. However, when informed by mosaic experimental data model predictions greatly vary illustrating the risks of using mosaic datasets from unrelated cell types.