bluuebunny/crossref_metadata_2025 huggingface dataset:
Acquired resistance to PRMT5 inhibition induces concomitant collateral sensitivity to paclitaxel
Authors: Mueller Helen S. , Fowler Colin E. , Dalin Simona , Moiso Enrico , Udomlumleart Tee , Garg Salil , Hemann Michael T. , Lees Jacqueline A.
Published: August 2021

Significance

Resistance to therapeutics is a challenge when treating cancer patients. Cancer can become resistant to therapies in distinct, unpredictable ways. Therefore, it is important to understand how resistance occurs to enable development of second-line or combination treatment strategies. This study develops cells that are resistant to inhibitors of protein arginine methyltransferase 5 (PRMT5), which is up-regulated in many cancers and being targeted in current clinical trials. We show that resistant lung adenocarcinoma cells are now sensitive to the widely used chemotherapy, paclitaxel, and identify a single gene,
Stmn2
, that is responsible for both the resistance to inhibitors of PRMT5 and the collateral sensitivity to paclitaxel. Our data suggest that combined treatment with PRMT5 inhibitors and taxanes could be a success.
Electricity consumption of Singaporean households reveals proactive community response to COVID-19 progression
Authors: Raman Gururaghav , Peng Jimmy Chih-Hsien
Published: August 2021

Significance

It is vital for policymakers to understand how people react during a pandemic. Here, we propose to use domestic electricity-consumption data, which arguably capture peoples’ daily behaviors accurately and dynamically. Considering the city-state of Singapore as a case study, we study over 10,200 individual households’ electricity-consumption patterns to uncover previously unknown behavioral trends during the COVID-19 pandemic. While providing implications for the design of public health interventions during this and other pandemics, our results imply a proactive response from the community, which is surprisingly consistent across all demographics. This cohesive response may have helped the city-state in effectively curtailing the disease, a learning that has direct implications on the pandemic response of other nations as well.
Insights into the bilayer-mediated toppling mechanism of a folate-specific ECF transporter by cryo-EM
Authors: Thangaratnarajah Chancievan , Rheinberger Jan , Paulino Cristina , Slotboom Dirk J.
Published: August 2021

Significance

Gram-positive bacteria that lack biosynthesis pathways for micronutrients such as vitamins use a class of membrane proteins to acquire them from the environment. These membrane proteins are called energy-coupling factor (ECF) transporters and function in an unusual way. A membrane-embedded substrate-binding protein rotates within the membrane to bring a molecule from the outside to the inside of the cell. It was, however, not clear how this motion can occur within a bilayer environment. We use cryogenic electron microscopy at 200 kV to visualize an ECF transporter within a lipid bilayer. The transporter causes deformations to the surrounding lipid environment. These insights offer an explanation for how changes of the lipid environment enable such motion in the transport process.
Elastically driven Kelvin–Helmholtz-like instability in straight channel flow
Authors: Jha Narsing K. , Steinberg Victor
Published: August 2021

Significance

Kelvin–Helmholtz instability (KHI) describes the growth of perturbations of the interface separating counterpropagating streams of Newtonian fluids with different velocities and densities with heavier fluid at the bottom. It is one of the most studied shear flow instabilities widespread in nature and industrial processes. The KHI mechanism is based on competition between destabilizing velocity difference and stabilizing stratification. We study KHI in channel shear flow of viscoelastic fluid, considered stable due to elastic stress generated by polymers stretched by shear strain. Contrary to generally accepted opinion, we discover the elastically driven KH-like instability with temporal dynamics similar to Newtonian KHI but driven by strikingly different elastically driven destabilizing mechanism of elastic wave interacting with wall-normal vorticity amplifying interface perturbations.
A Proposal for Relative In-flight Flux Self-calibrations for Spectro-photometric Surveys
Authors: Davini S , Risso I , Scodeggio M , Paganin L , Caprioli S , Bonici M , Caminata A , Di Domizio S , Testera G , Tosi S , Valerio B , Fumana M , Franzetti P
Published: August 2021

We present a method for the in-flight relative flux self-calibration of a spectro-photometer instrument, general enough to be applied to any upcoming galaxy survey on satellite. The instrument response function, that accounts for a smooth continuous variation due to telescope optics, on top of a discontinuous effect due to the segmentation of the detector, is inferred with a χ
2 statistics. The method provides unbiased inference of the sources count rates and of the reconstructed relative response function, in the limit of high count rates. We simulate a simplified sequence of observations following a spatial random pattern and realistic distributions of sources and count rates, with the purpose of quantifying the relative importance of the number of sources and exposures for correctly reconstructing the instrument response. We present a validation of the method, with the definition of figures of merit to quantify the expected performance, in plausible scenarios.
Estimating the contribution of traffic flow to pollutant concentrations
Authors: Khataan Ahmed , Idris Ahmed O , Abo Elazm Mohamed M , Kamel Wael
Published: August 2021

The rapid increase in vehicular use due to human activities in urban areas has been leading to a worsening in air quality, thus negatively affect the exposure of inhabitants to polluted air and also harms the environment. This work studies the contribution of traffic flow on CO and NO2 concentration. The field measurement of both pollutants was considered in a roughly isolated street canyon. In addition, the meteorological parameters of the studied location were collected parallel with traffic flow data. There have been days in which the study location was affected by traffic flow and some others were not affected. In particular, statistical tests and data analysis were applied to the collected dataset after splitting it into two groups. One with zero traffic flow and the other with a significant variation in traffic flow. Also, the effect of meteorological parameters such as wind speed, wind direction, ambient temperature, and relative humidity on pollutant concentrations was considered. Moreover, the multivariate linear regression models were developed for both pollutants to address the contribution of each factor. As a result, the positive effect of traffic flow and the negative effect of the wind directions highly improves the prediction of the near-road traffic-related pollutant concentration.
Effects of spraying Indonesian foliar fertilizer on growth and quality of tea in red soil region of southern China
Authors: Huang Dongfeng , Wang Limin , Li Yu , Pan Zhucai , Lin Zuoqi
Published: August 2021

In order to explore the application effect of BioSilAc solid foliar fertilizer and OBFs liquid foliar fertilizer produced by Indonesia Institute of Biotechnology and Bio-industry on tea plantations in red soil region, a field plot experiment was conducted to study the effects of spraying BioSilAc and OBFs on the morphological indexes of tea garden, fresh tea outputs and contents of biochemical components of tea in red soil region of southern China. Results showed that spraying BioSilAc and OBFs could increase bud density by 14.4%-24%, 100 buds’ weight of tea by 17.0%-33.9%, internode length by 9.5%-23.8% and leaf area by 6.9%-23.1%, respectively; The yield of autumn tea and spring tea increased by 2.4%-6.7% and 13.1%-24.7% respectively, and the total yield of fresh tea was increased by 7.1%-14.5%; The contents of tea polyphenols, amino acids, caffeine and water extract were increased by 8.3%-24.0%, 19.0%-47.6%, 3.5%-19.7% and 13.2%-31.3%, respectively. Among them, treatment of CF+OBFs had the best effect on improving the morphological indexes of tea gardens, promoting the yield and increasing the content of biochemical components of tea.
Effects of clint on the distribution and leaf phenotypic variation of a dominant plant Lindera communis in Maolan Karst National Natural Reserve, SW China
Authors: Yu Xiaoya , Li Yuhui , Zeng Xiao-hong
Published: August 2021

The heterogeneous habitat plays an important role in the conservation and restoration for rare and endangered plant species. In the karst area, the clints usually cause the soil differentiation of physical and chemical properties, which affect the distribution and adaptation strategy of dominant plant populations. To study the distribution and adaptation strategy of the dominant plants in heterogeneous habitats induced by clints, we investigated the leaf phenotypic variation along the transect from Lindera communis plant to clint (0 cm, 0.1cm-10cm and ≥ 10 cm) within the Maolan Karst National Nature Reserve, Libo County, Guizhou Province, China. The results showed: (1) 483 individuals of L. communis had been recorded, and the trees (DBH≥1cm) were 374 individuals (77.43% of the total). The DBH of biggest L. communis was 10.5cm, which was 6 cm away from the clint. In the 0cm distance group, the tree (mean DBH 2.97±1.71 cm) were 200, and the seedlings and saplings were 29. In the 0.1cm-10cm distance group, the tree (mean DBH 2.75±1.62 cm) were 50, and the seedlings and saplings were 44. In the ≥ 10cm distance group, the tree (mean DBH 2.52±1.29 cm) were 124, and seedlings and saplings were 36. The mean DBH of L. communis individuals was decreased with the increase of the distance between plant and clint. The coefficients of variation of L. communis individuals DBH in each distance group, which indicated that the DBH distribution of this species was uncertain at different groups. (2) The leaf length, width, width/length and thickness of L. communis was 79.71±12.95 mm, 30.17±6.68 mm, 0.38±0.07, 0.24±0.05 mm, respectively. The petiole length and diameter of L. communis was 6.65±1.87 mm and 1.19±0.63 mm, respectively. The coefficient of variation of petiole length increased first and then decreased with the distance from clint increasing. Meanwhile, the variation coefficients of leaf length, leaf width, leaf width/length, leaf thickness and petiole diameter decreased first and then increased with the increase of distance from clint. The distance between the clint and L. communis had significant effect on the leaf length (P < 0.05), and thickness (P < 0.01) and width/length (P < 0.01), and had minor effect on the other leaf traits. The present study highlighted that the clint had a profound influence effect on the distribution and leaf characteristics traits of L. communis. Therefore, we can use the clint as a key node to protect and restore the plant population size.
Exploring the quantitative assessment of urban economic vitality in the Yangtze River Delta of China based on PCA
Authors: Liu Shaojun , Liu Hao , Long Yao
Published: August 2021

With the accelerating urbanization in developing countries, sustainable urban development has become a strategic goal for governments. To promote sustainable development of individual cities, it is necessary to break away from the limitations of administrative divisions and use the synergistic effect of urban clusters to solve the many difficulties facing sustainable development. The assessment of economic vitality is a critical way to evaluate the development potential of cities. This paper proposes a quantitative assessment method for urban economic vitality. Using 26 cities in the Yangtze River Delta region as the research object and local statistical yearbooks as the data source, we construct 18 urban economic vitality assessment indicators. First, we use the Principal Component Analysis (PCA) method to obtain the five major factors of city vitality assessment: manufacturing and people’s life factor, service industry and government management factor, industrial economic growth rate factor, urban development potential factor and primary and secondary industry efficiency factor. Then, we use spatial hotspot analysis to classify the urban economic vitality of the Yangtze River Delta region into three categories: low, medium and high. The research results have important implications for the coordinated and sustainable development of the regional economy and the formulation of economic development strategies for low-vitality regions.
Ecological sustainable significance of rain garden design in Lingnan primary and secondary schools from foreign cases
Authors: Zang Guyuxin , Guan Shaoping
Published: August 2021

Based on the research of the rain garden in Mount Tabor middle school, Nueva primary school, and Delta North Delta school district, this work summarized the design strategy and ecological sustainable significance of rain garden in the case from three aspects: design method, educational benefit, and ecological benefit. Finally, the design approach of rain garden in Lingnan primary and secondary schools and its significance to the sustainable development of ecological education and ecological protection were proposed.
Analysis of sedimentary facies characteristics and source reservoir allocation of fault depressed Lake Basin—Taking Xu-Xi area of Songliao Basin as an example
Authors: Tian Ya
Published: August 2021

At present, Xu-Xi area is in the primary stage of exploration, and its sedimentary characteristics and distribution law are not clear. In this study, based on the analysis of regional structural background, through core observation and description, grain size analysis, well logging and seismic and other technical means, the sedimentary facies types and spatial distribution characteristics of Shahezi Formation in Xu-Xi area are studied. It is believed that there are three types of sedimentary systems in Shahezi Formation in the study area: Fan Delta, braided river delta and lake. The fan delta is mainly developed in the steep slope belt in the west of Xu-Xi area, while the braided river delta is mainly developed in the gentle slope belt in the East and the axial belt in the north, and the lake facies is developed in the depression belt between them. On the whole, the sedimentary pattern shows the obvious characteristics of “North-South block, east-west belt”. From the West steep slope to the East gentle slope, the sedimentary facies type transits from fan delta to deep lake semi deep lake and then to Braided River Delta. Combined with the study of reservoir forming conditions, it is found that the sand bodies of fan delta front and braided river delta front have good reservoir physical properties and are often adjacent to large-scale high-quality source rocks in the upper and lower or lateral directions. The reservoir forming conditions are superior and are favorable for oil and gas accumulation facies belt.
Corrigendum: Development of ecosystem for effective supply chains in 3D printing industry – an ISM approach (2021 IOP Conf. Ser.: Mater Sci Eng. 1136 012049)
Authors: Singh S , Agrawal V
Published: August 2021

Please see Article PDF for corrigendum text.
An innovative alcohol-solution combustion-calcination process for the fabrication of NiFe2O4 nanorods and their adsorption characteristics of methyl blue in aqueous solution
Authors: Xu Qi , Xu Yueyang , Xue Jianming , Zhu Fahua , Zhong Zhaoping , Liu Ruijiang
Published: August 2021

Magnetic nickel ferrite (NiFe2O4) nanorods were prepared via an innovative alcohol-solution combustion-calcination technique and evaluated for removing methyl blue (MB), which may greatly benefit for dye-polluted water treatment. The magnetic nanorods were characterized by TEM, EDS, XRD, VSM, SAED, FTIR, XPS and BET, the results showed that the NiFe2O4 sample has high magnetic saturation (Ms) and soft superparamagnetic behavior, and these properties accounted for their facile separation from the aqueous solution when an external magnetic field was applied. To understand the adsorption mechanism, adsorption experiments were performed using adsorption kinetics and adsorption isotherms. The Temkin model and the pseudo-second-order kinetic model best described the adsorption characteristics of MB onto NiFe2O4 nanorods. The effect of pH on the adsorption process was investigated, when pH was 3–7, the maximum adsorption capacity was reached, which was about 62 mg·g−1. The recycling efficiency was also estimated, after 10 runs of regeneration, it remained 70.1% initial adsorption capacity, indicating the adsorbent could be efficiently reused for the adsorption of MB.
Optimal Hölder regularity for the ∂̄ problem on product domains in ℂ²
Authors: Zhang Yuan
Published: August 2021

The note concerns the

∂
¯

\bar \partial

problem on product domains in

C

2

\mathbb C^2

. We show that there exists a bounded solution operator from

C

k
,
α

C^{k, \alpha }

into itself,

k
∈

Z

+

∪
{
0
}
,
0
>
α
>
1

k\in \mathbb Z^+\cup \{0\}, 0>\alpha > 1

. The regularity result is optimal in view of an example of Stein-Kerzman.
Adherence to self-administered biologic disease-modifying antirheumatic drugs across health-system specialty pharmacies
Authors: Zuckerman Autumn D , DeClercq Josh , Choi Leena , Cowgill Nicole , McCarthy Kate , Lounsbery Brian , Shah Rushabh , Kehasse Amanuel , Thomas Karen C , Sokos Louis , Stutsky Martha , Young Jennifer , Carter Jennifer , Lach Monika , Wise Kelly , Thomas Toby T , Ortega Melissa , Lee Jinkyu , Lewis Kate , Dura Jillian , Gazda Nicholas P , Gerzenshtein Lana , Canfield Scott
Published: August 2021

Purpose

Adherence to self-administered biologic disease-modifying antirheumatic drugs (bDMARDs) is necessary for therapeutic benefit. Health-system specialty pharmacies (HSSPs) have reported high adherence rates across several disease states; however, adherence outcomes in rheumatoid arthritis (RA) populations have not yet been established.

Methods

We performed a multisite retrospective cohort study including patients with RA and 3 or more documented dispenses of bDMARDs from January through December 2018. Pharmacy claims were used to calculate proportion of days covered (PDC). Electronic health records of patients with a PDC of <0.8 were reviewed to identify reasons for gaps in pharmacy claims (true nonadherence or appropriate treatment holds). Outcomes included median PDC across sites, reasons for treatment gaps in patients with a PDC of <0.8, and the impact of adjusting PDC when accounting for appropriate therapy gaps.

Results

There were 29,994 prescriptions for 3,530 patients across 20 sites. The patient cohort was mostly female (75%), with a median age of 55 years (interquartile range [IQR], 42-63 years). The median PDC prior to chart review was 0.94 (IQR, 0.83-0.99). Upon review, 327 patients had no appropriate treatment gaps identified, 6 patients were excluded due to multiple unquantifiable appropriate gaps, and 420 patients had an adjustment in the PDC denominator due to appropriate treatment gaps (43 instances of days’ supply adjusted based on discordant days’ supply information between prescriptions and physician administration instructions, 11 instances of missing fills added, and 421 instances of clinically appropriate treatment gaps). The final median PDC after accounting for appropriate gaps in therapy was 0.95 (IQR, 0.87-0.99).

Conclusion

This large, multisite retrospective cohort study was the first to demonstrate adherence rates across several HSSPs and provided novel insights into rates and reasons for appropriate gaps in therapy.
Differential modulation of the lipoxygenase cascade during typical and latentPectobacterium atrosepticuminfections
Authors: Gorshkov Vladimir Y , Toporkova Yana Y , Tsers Ivan D , Smirnova Elena O , Ogorodnikova Anna V , Gogoleva Natalia E , Parfirova Olga I , Petrova Olga E , Gogolev Yuri V
Published: August 2021

Background and Aims

Plant diseases caused by Pectobacterium atrosepticum are often accompanied by extensive rot symptoms. In addition, these bacteria are able to interact with host plants without causing disease for long periods, even throughout several host plant generations. There is, to date, no information on the comparative physiology/biochemistry of symptomatic and asymptomatic plant–P. atrosepticum interactions. Typical (symptomatic) P. atrosepticum infections are associated with the induction of plant responses mediated by jasmonates, which are one of the products of the lipoxygenase cascade that gives origin to many other oxylipins with physiological activities. In this study, we compared the functioning of the lipoxygenase cascade following typical and latent (asymptomatic) infections to gain better insight into the physiological basis of the asymptomatic and antagonistic coexistence of plants and pectobacteria.

Methods

Tobacco plants were mock-inoculated (control) or infected with the wild type P. atrosepticum (typical infection) or its coronafacic acid-deficient mutant (latent infection). The expression levels of the target lipoxygenase cascade-related genes were assessed by Illumina RNA sequencing. Oxylipin profiles were analysed by GC-MS. With the aim of revising the incorrect annotation of one of the target genes, its open reading frame was cloned to obtain the recombinant protein, which was further purified and characterized using biochemical approaches.

Key Results

The obtained data demonstrate that when compared to the typical infection, latent asymptomatic P. atrosepticum infection is associated with (and possibly maintained due to) decreased levels of 9-lipoxygenase branch products and jasmonic acid and increased level of cis-12-oxo-10,15-phytodienoic acid. The formation of 9-oxononanoic acid and epoxyalcohols in tobacco plants was based on the identification of the first tobacco hydroperoxide lyase (HPL) with additional epoxyalcohol synthase (EAS) activity.

Conclusions

Our results contribute to the hypothesis of the oxylipin signature, indicating that different types of plant interactions with a particular pathogen are characterized by the different oxylipin profiles of the host plant. In addition, the tobacco LOC107825278 gene was demonstrated to encode an NtHPL (CYP74C43) enzyme yielding volatile aldehydes and aldoacids (HPL products) as well as oxiranyl carbinols (EAS products).
Is seasonal flowering time of Paphiopedilum species caused by differences in initial time of floral bud differentiation?
Authors: Feng Jing-Qiu , Xia Qian , Zhang Feng-Ping , Wang Ji-Hua , Zhang Shi-Bao
Published: August 2021

Members of the genus Paphiopedilum are world-famous for their large, colourful flowers, unique floral morphology and long floral lifespan. Most Paphiopedilum species bloom in spring or autumn. The control of flowering time is of great significance to the commercial production of floral crops, because it affects the sales and prices of flowers. However, the mechanism that regulates when Paphiopedilum species bloom is unclear. In the present study, floral bud initiation and development of P. micranthum (spring-flowering species with one flower per stalk), P. dianthum (autumn-flowering species with multiple flowers per stalk) and P. henryanum (autumn-flowering species with one flower per stalk) were investigated by morphological and anatomical methods. We divided Paphiopedilum floral bud differentiation into six phases: the initiation of differentiation, inflorescence primordium differentiation, flower primordium differentiation, sepal primordium differentiation, petal primordium differentiation and column primordium differentiation. We found that the timing of floral bud differentiation for the three species was synchronized when experiencing the same environment, while the period from initiation to flowering largely differed. In addition, initiation of floral bud differentiation in P. dianthum was earlier at a warmer environment. The difference in flowering time of three species was mainly caused by the duration of floral bud development, rather than the initiation time. The findings were of great significance for the cultivation and flowering regulation of Paphiopedilum species.
A compositional mediation model for a binary outcome: Application to microbiome studies
Authors: Sohn Michael B , Lu Jiarui , Li Hongzhe
Published: August 2021

Motivation

The delicate balance of the microbiome is implicated in our health and is shaped by external factors, such as diet and xenobiotics. Therefore, understanding the role of the microbiome in linking external factors and our health conditions is crucial to translate microbiome research into therapeutic and preventative applications.

Results

We introduced a sparse compositional mediation model for binary outcomes to estimate and test the mediation effects of the microbiome utilizing the compositional algebra defined in the simplex space and a linear zero-sum constraint on probit regression coefficients. For this model with the standard causal assumptions, we showed that both the causal direct and indirect effects are identifiable. We further developed a method for sensitivity analysis for the assumption of the no unmeasured confounding effects between the mediator and the outcome. We conducted extensive simulation studies to assess the performance of the proposed method and applied it to real microbiome data to study mediation effects of the microbiome on linking fat intake to overweight/obesity.

Availability and implementation

An R package can be downloaded from https://github.com/mbsohn/cmmb.

Supplementary information

Supplementary files are available at Bioinformatics online.
Dimethyl fumarate treatment restrains the antioxidative capacity of T cells to control autoimmunity
Authors: Liebmann Marie , Korn Lisanne , Janoschka Claudia , Albrecht Stefanie , Lauks Sarah , Herrmann Alexander M , Schulte-Mecklenbeck Andreas , Schwab Nicholas , Schneider-Hohendorf Tilman , Eveslage Maria , Wildemann Brigitte , Luessi Felix , Schmidt Stephan , Diebold Martin , Bittner Stefan , Gross Catharina C , Kovac Stjepana , Zipp Frauke , Derfuss Tobias , Kuhlmann Tanja , König Simone , Meuth Sven G , Wiendl Heinz , Klotz Luisa
Published: August 2021

Dimethyl fumarate, an approved treatment for relapsing-remitting multiple sclerosis, exerts pleiotropic effects on immune cells as well as CNS resident cells.

Here, we show that dimethyl fumarate exerts a profound alteration of the metabolic profile of human CD4+ as well as CD8+ T cells and restricts their antioxidative capacities by decreasing intracellular levels of the reactive oxygen species scavenger glutathione. This causes an increase in mitochondrial reactive oxygen species levels accompanied by an enhanced mitochondrial stress response, ultimately leading to impaired mitochondrial function. Enhanced mitochondrial reactive oxygen species levels not only result in enhanced T-cell apoptosis in vitro as well as in dimethyl fumarate-treated patients, but are key for the well-known immunomodulatory effects of dimethyl fumarate both in vitro and in an animal model of multiple sclerosis, i.e. experimental autoimmune encephalomyelitis. Indeed, dimethyl fumarate immune-modulatory effects on T cells were completely abrogated by pharmacological interference of mitochondrial reactive oxygen species production.

These data shed new light on dimethyl fumarate as bona fide immune-metabolic drug that targets the intracellular stress response in activated T cells, thereby restricting mitochondrial function and energetic capacity, providing novel insight into the role of oxidative stress in modulating cellular immune responses and T cell-mediated autoimmunity.
Physiological response and survival of Atlantic mackerel exposed to simulated purse seine crowding and release
Authors: Anders Neil , Roth Bjørn , Breen Mike
Published: August 2021

Understanding how animals physiologically respond to capture and release from wild capture fishing is fundamental for developing practices that enhance their welfare and survival. As part of purse seine fishing for small pelagic fish in northern European waters, excess and/or unwanted catches are routinely released from the net in a process called slipping. Due to excessive crowding in the net prior to release, post-slipping mortality rates can be unacceptably high. Atlantic mackerel (Scomber scombrus) support large and economically important purse seine fisheries but are known to be particularly vulnerable to such crowding-induced mortality. Developing management advice to promote post-slipping survival for this species is currently challenging, due to a lack of understanding of how crowding influences their physiology. Here we examine the physiological response, recovery and survival of wild caught mackerel exposed to various degrees and durations of simulated crowding stress in a series of sea cage trials. The magnitude of the physiological response and its time to recovery was positively correlated with crowding density and duration and was characterized by cortisol elevation, energy mobilization and anaerobic metabolite accumulation. There were also indications of osmoregulatory disturbance. Skin injury and mortality rates showed a similar positive relationship to crowding density. The physiological disturbance was recoverable for most fish. Instead, the rate at which mortalities developed and the physiological profile of moribund fish indicated that skin injury, likely arising from abrasive contact with netting and other fish during crowding, was the probable cause of mortality. Injured fish also exhibited a loss of allometric condition relative to non-injured survivors. Crowding treatments were potentially confounded by differences in ambient oxygen reduction, water temperature and pre-treatment fish condition between trials, and densities were replicated only once. These results contribute to the development of welfare conscious fishing practices that aim to reduce post-slipping mortality.
Down-regulation of AMPK/PPARδ signalling promotes endoplasmic reticulum stress-induced endothelial dysfunction in adult rat offspring exposed to maternal diabetes
Authors: Luo Hao , Lan Cong , Fan Chao , Gong Xue , Chen Caiyu , Yu Cheng , Wang Jialiang , Luo Xiaoli , Hu Cuimei , Jose Pedro A , Xu Zaicheng , Zeng Chunyu
Published: August 2021

Aims

Exposure to maternal diabetes is associated with increased prevalence of hypertension in the offspring. The mechanisms underlying the prenatal programming of hypertension remain unclear. Because endoplasmic reticulum (ER) stress plays a key role in vascular endothelial dysfunction in hypertension, we investigated whether aberrant ER stress causes endothelial dysfunction and high blood pressure in the offspring of dams with diabetes.

Methods and results

Pregnant Sprague-Dawley rats were intraperitoneally injected with streptozotocin (35 mg/kg) or citrate buffer at Day 0 of gestation. Compared with control mother offspring (CMO), the diabetic mother offspring (DMO) had higher blood pressure and impaired endothelium-dependent relaxation in mesenteric arteries, accompanied by decreased AMPK phosphorylation and PPARδ expression, increased ER stress markers, and reactive oxygen species (ROS) levels. The inhibition of ER stress reversed these aberrant changes in DMO. Ex vivo treatment of mesenteric arteries with an AMPK agonist (A769662) or a PPARδ agonist (GW1516) improved the impaired EDR in DMO and reversed the tunicamycin-induced ER stress, ROS production, and EDR impairment in mesenteric arteries from CMO. The effects of A769662 were abolished by co-treatment with GSK0660 (PPARδ antagonist), whereas the effects of GW1516 were unaffected by Compound C (AMPK inhibitor).

Conclusion

These results suggest an abnormal foetal programming of vascular endothelial function in offspring of rats with maternal diabetes that is associated with increased ER stress, which can be ascribed to down-regulation of AMPK/PPARδ signalling cascade.
A patient with pulmonary embolism takes a surprising HIT: a case report
Authors: Wasserstrum Yishay , Lubetzky Aaron , Goitein Orly , Matetzky Shlomo
Published: August 2021

Background

Venous thromboembolism (VTE) is a common condition that may manifest as intermediate or high-risk pulmonary embolism (PE), requiring either primary or subsequent fibrinolytic therapy. In these cases, catheter-directed thrombolysis (CDT) has been shown to be beneficial.

Case summary

We present the case of a borderline obese but otherwise healthy 43-year-old male individual, who was admitted with acute intermediate- to high-risk PE requiring treatment with intravenous unfractionated heparin. After initial therapy failure, the patient received CDT, with subsequent clinical worsening, and a mixed result of imaging studies suggesting partial central worsening and partial peripheral improvement of the thrombotic burden and right ventricular (RV) function. After a multidisciplinary PE response team (PERT) consultation, the diagnosis of heparin-induced thrombocytopenia (HIT) with normal platelet levels was made. Therapy was changed to intravenous bivalirudin, with an excellent clinical response and complete recovery of RV function. The patient was discharged with oral rivaroxaban therapy, and on follow-up was otherwise well.

Discussion

Apparent failure of thrombolytic therapy for VTE warrants a clinical investigation into possible causes of a pro-thrombotic state. In this case, the diagnosis of HIT was surprising, especially due to only a mild decline in platelet levels that were well within normal range. We also acknowledge the significance of our PERT in the key diagnosis made in this case.
Patient-reported outcomes, clinical, and demographic variables as predictors of withdrawal from the workforce after hospitalization with heart failure: findings from the national DenHeart survey
Authors: Tjustrup Nina Cecilie , Engel Schmidt Signe , Christensen Anne Vingaard , Rasmussen Trine Bernholdt , Borregaard Britt , Thrysoee Lars , Mols Rikke Elmose , Thorup Charlotte Brun , Juel Knud , Ankerstjerne Anne , Berg Selina Kikkenborg
Published: August 2021

Aims

Increased prevalence and survival among patients with heart failure draws attention to their everyday life, including their ability to work. Many patients with heart failure withdraw from the workforce, which can affect their quality of life. The aim was to investigate patient-reported outcomes (PROs) and clinical and demographic variables as predictors of withdrawal from the workforce after admission with a diagnose of heart failure.

Methods and results

Patients with heart failure, who were part of the workforce at admission were included from the national cross-sectional survey, DenHeart. Data were collected from five national heart centres in Denmark, from April 2013 to April 2014. Patient-reported outcomes measured at discharge included SF-12, HeartQoL, HADS, and ESAS. Clinical and demographic variables were obtained from registers, medical records, and index hospitalization. Patient-reported outcomes, clinical, and demographic variables were combined with labour market affiliation 3, 6, 9, and 12 months after admission. The response rate was 49.1% (n = 1517) and of those 364 patients were part of the workforce at index admission. Patients with lower QoL odds ratio (OR) 2.58 [95% confidence interval (CI) 1.24–5.37], symptoms of depression OR 2.57 (95% CI 1.47–4.50) and ejection fraction (EF) ≤35% OR 2.48 (95% CI 1.35–4.56) were more likely to withdraw from the workforce in the first year after admission. Patients with lower symptom burden OR 0.36 (95% CI 0.19–0.68) and a hospital stay of 0–2 days OR 0.18(95% CI 0.08–0.37) were less likely to withdraw.

Conclusion

Low QoL, high symptom burden, symptoms of depression, a longer length of hospital stay, and low EF can predict withdrawal from the workforce in the first year after admission with heart failure.
Genomic and molecular evidence reveals novel pathways associated with cell surface polysaccharides in bacteria
Authors: Simunović Vesna
Published: August 2021

Amino acid (acyl carrier protein) ligases (AALs) are a relatively new family of bacterial amino acid adenylating enzymes with unknown function(s). Here, genomic enzymology tools that employ sequence similarity networks and genome context analyses were used to hypothesize the metabolic function(s) of AALs. In over 50% of species, aal and its cognate acyl carrier protein (acp) genes, along with three more genes, formed a highly conserved AAL cassette. AAL cassettes were strongly associated with surface polysaccharide gene clusters in Proteobacteria and Actinobacteria, yet were prevalent among soil and rhizosphere-associated α- and β-Proteobacteria, including symbiotic α- and β-rhizobia and some Mycolata. Based on these associations, AAL cassettes were proposed to encode a noncanonical Acp-dependent polysaccharide modification route. Genomic-inferred predictions were substantiated by published experimental evidence, revealing a role for AAL cassettes in biosynthesis of biofilm-forming exopolysaccharide in pathogenic Burkholderia and expression of aal and acp genes in nitrogen-fixing Rhizobium bacteroids. Aal and acp genes were associated with dltBD-like homologs that modify cell wall teichoic acids with d-alanine, including in Paenibacillus and certain other bacteria. Characterization of pathways that involve AAL and Acp may lead to developing new plant and human disease-controlling agents as well as strains with improved nitrogen fixation capacity.
Global analysis of Saccharomyces cerevisiae growth in mucin
Authors: Mercurio Kevin , Singh Dylan , Walden Elizabeth , Baetz Kristin
Published: August 2021

Metagenomic profiling of the human gut microbiome has discovered DNA from dietary yeasts like Saccharomyces cerevisiae. However, it is unknown if the S. cerevisiae detected by common metagenomic methods are from dead dietary sources, or from live S. cerevisiae colonizing the gut similar to their close relative Candida albicans. While S. cerevisiae can adapt to minimal oxygen and acidic environments, it has not been explored whether this yeast can metabolize mucin, the large, gel-forming, highly glycosylated proteins representing a major source of carbon in the gut mucosa. We reveal that S. cerevisiae can utilize mucin as their main carbon source, as well as perform both a transcriptome analysis and a chemogenomic screen to identify biological pathways required for this yeast to grow optimally in mucin. In total, 739 genes demonstrate significant differential expression in mucin culture, and deletion of 21 genes impact growth in mucin. Both screens suggest that mitochondrial function is required for proper growth in mucin, and through secondary assays we determine that mucin exposure induces mitogenesis and cellular respiration. We further show that deletion of an uncharacterized ORF, YCR095W-A, led to dysfunction in mitochondrial morphology and oxygen consumption in mucin. Finally, we demonstrate that Yps7, an aspartyl protease and homolog to mucin-degrading proteins in C. albicans, is important for growth on mucin. Collectively, our work serves as the initial step toward establishing how this common dietary fungus can survive in the mucus environment of the human gut.
Crafting for a better MAGIC: systematic design and test for Multiparental Advanced Generation Inter-Cross population
Authors: Yang Chin Jian , Edmondson Rodney N , Piepho Hans-Peter , Powell Wayne , Mackay Ian
Published: August 2021

Multiparental Advanced Generation Inter-Cross (MAGIC) populations are valuable crop resources with a wide array of research uses including genetic mapping of complex traits, management of genetic resources and breeding of new varieties. Multiple founders are crossed to create a rich mosaic of highly recombined founder genomes in the MAGIC recombinant inbred lines (RILs). Many variations of MAGIC population designs exist; however, a large proportion of the currently available populations have been created empirically and based on similar designs. In our evaluations of five MAGIC populations, we found that the choice of designs has a large impact on the recombination landscape in the RILs. The most popular design used in many MAGIC populations has been shown to have a bias in recombinant haplotypes and low level of unique recombinant haplotypes, and therefore is not recommended. To address this problem and provide a remedy for the future, we have developed the “magicdesign” R package for creating and testing any MAGIC population design via simulation. A Shiny app version of the package is available as well. Our “magicdesign” package provides a unifying tool and a framework for creativity and innovation in MAGIC population designs. For example, using this package, we demonstrate that MAGIC population designs can be found which are very effective in creating haplotype diversity without the requirement for very large crossing programs. Furthermore, we show that interspersing cycles of crossing with cycles of selfing is effective in increasing haplotype diversity. These approaches are applicable in species that are hard to cross or in which resources are limited.
RNAProt: an efficient and feature-rich RNA binding protein binding site predictor
Authors: Uhl Michael , Tran Van Dinh , Heyl Florian , Backofen Rolf
Published: August 2021

Background

Cross-linking and immunoprecipitation followed by next-generation sequencing (CLIP-seq) is the state-of-the-art technique used to experimentally determine transcriptome-wide binding sites of RNA-binding proteins (RBPs). However, it relies on gene expression, which can be highly variable between conditions and thus cannot provide a complete picture of the RBP binding landscape. This creates a demand for computational methods to predict missing binding sites. Although there exist various methods using traditional machine learning and lately also deep learning, we encountered several problems: many of these are not well documented or maintained, making them difficult to install and use, or are not even available. In addition, there can be efficiency issues, as well as little flexibility regarding options or supported features.

Results

Here, we present RNAProt, an efficient and feature-rich computational RBP binding site prediction framework based on recurrent neural networks. We compare RNAProt with 1 traditional machine learning approach and 2 deep-learning methods, demonstrating its state-of-the-art predictive performance and better run time efficiency. We further show that its implemented visualizations capture known binding preferences and thus can help to understand what is learned. Since RNAProt supports various additional features (including user-defined features, which no other tool offers), we also present their influence on benchmark set performance. Finally, we show the benefits of incorporating additional features, specifically structure information, when learning the binding sites of an hairpin loop binding RBP.

Conclusions

RNAProt provides a complete framework for RBP binding site predictions, from data set generation over model training to the evaluation of binding preferences and prediction. It offers state-of-the-art predictive performance, as well as superior run time efficiency, while at the same time supporting more features and input types than any other tool available so far. RNAProt is easy to install and use, comes with comprehensive documentation, and is accompanied by informative statistics and visualizations. All this makes RNAProt a valuable tool to apply in future RBP binding site research.
Exploring the potential of citizen science for public health through an alcohol advertising case study
Authors: Thomas Jessica A , Trigg Joshua , Morris Julia , Miller Emma , Ward Paul R
Published: August 2021

Citizen science connects academic researchers with the public through combined efforts in scientific inquiry. The importance of involving impacted populations in health research is well established. However, how to achieve meaningful participation and the methodological impact of citizen science needs further examination. We examined the feasibility of using citizen science to understand the impact of alcohol advertising on Australian women through a breast cancer prevention project. Two hundred and eighty-two (‘participants’) citizen scientists completed demographic and behavioural questions via an online survey. The research participants moved into the role of citizen scientists by completing the data collection tasks of capturing and classifying images of alcohol advertising they saw online. Interrater reliability tests found high levels of agreement between citizen scientists and academic researchers with the classification of alcohol advertising brand (Kappa = 0.964, p < 0.001) and image type (Kappa = 0.936, p < 0.000). The citizen scientists were women aged 18 and over, with 62% between 35 and 55 years old. The majority were from major cities (78%), had attained a bachelor’s degree or higher-level education (62%) and were recruited via email or Facebook (86%). The use of citizen science provided methodological gains through the creation of a unique dataset with higher levels of validity than the existing literature, which employed traditional investigator-driven research methodologies. Citizen science enriched the dataset and provided a powerful methodological vehicle to understand an environmental determinant of health. The study illuminates how public participation benefitted the research process, the challenges and the potential for citizen science to improve public health.
TIDE Analysis of Cryptosporidium Infections by gp60 Typing Reveals Obscured Mixed Infections
Authors: Dettwiler Ines , Troell Karin , Robinson Guy , Chalmers Rachel M , Basso Walter , Rentería-Solís Zaida Melina , Daugschies Arwid , Mühlethaler Konrad , Dale Mariko I , Basapathi Raghavendra Jyothi , Ruf Marie-Thérèse , Poppert Sven , Meylan Mireille , Olias Philipp
Published: August 2021

Background

Cryptosporidiosis is a parasitic disease associated with potentially fatal diarrhea. The most used method in Cryptosporidium subtyping is based on the glycoprotein gene gp60. Each infection can represent a parasite population, and it is important to investigate the influence on transmission and virulence, as well as any impact on public health investigations. However, an easy-to-use method for detection is lacking.

Methods

Here we report on the use of the bioinformatic program TIDE for deconvolution of gp60 chromatograms. A combination of single oocyst analysis and cloning successfully confirmed the within-sample parasite population diversity. Retrospective sample analysis was conducted on archived chromatograms.

Results

For Cryptosporidium parvum, 8.6% multistrain infections (13 of 152) obscured by currently used consensus base calling were detected. Importantly, we show that single oocysts can harbor a mixed population of sporozoites. We also identified a striking dominance of unappreciated polymerase stutter artefacts in all 218 chromatograms analyzed, challenging the uncritical use of gp60 typing.

Conclusions

We demonstrate the value of a new, easy-to-use analytical procedure for critical characterization of C. parvum and Cryptosporidium hominis in epidemiological investigations, also applicable retrospectively. Our findings illuminate the hidden parasite diversity with important implications for tracing zoonotic and person-to-person transmissions.