bluuebunny/crossref_metadata_2025 huggingface dataset:
Indoor spectroradiometric characterization of plastic litters commonly polluting the Mediterranean Sea: toward the application of multispectral imagery
Authors: Corbari L. , Maltese A. , Capodici F. , Mangano M. C. , Sarà G. , Ciraolo G.
Published: November 2020

Around 350 million tonnes of plastics are annually produced worldwide. A remarkable percentage of these products is dispersed in the environment, finally reaching and dispersed in the marine environment. Recent field surveys detected microplastics’ concentrations in the Mediterranean Sea. The most commonly polymers found were polyethylene, polypropylene and viscose, ethylene vinyl acetate and polystyrene. In general, the in-situ monitoring of microplastic pollution is difficult and time consuming. The main goals of this work were to spectrally characterize the most commonly polymers and to quantify their spectral separability that may allow to determine optimal band combinations for imaging techniques monitoring. The spectral signatures of microplastics have been analysed in laboratory, both in dry condition and on water surface, using a full spectrum spectroradiometer. The theoretical use of operational satellite images for remote sensing monitoring was investigated by quantifying the spectral separability achievable by their sensors. The WorldView-3 sensor appears the most suitable for the monitoring but better average spectral separability are expected using the recently released PRISMA images. This research was preparatory to further outdoor experiments needed to better simulate the real acquisition condition.
Oncologic and obstetric outcomes after conization for adenocarcinoma in situ or stage IA1 cervical cancer
Authors: Wang Xiaoyu , Bi Yalan , Wu Huanwen , Wu Ming , Li Lei
Published: November 2020

This study aims to reveal the risk factors associated with recurrence or new-onset high-grade squamous intraepithelial lesions (HSILs) or more severe lesions (HSILs +) and analyze obstetrical outcomes in patients with adenocarcinoma in situ (AIS) or stage IA1 cervical cancer patients after conization. A retrospective cohort study was developed from January 1, 2002, and July 1, 2018, in a single center, where all patients with AIS or stage IA1 cervical cancer who accepted conization for primary surgery were reviewed and followed up until July 1, 2019, for the pathological findings of HSILs + and obstetric outcomes. Two hundred and seventeen patients were identified, including 114 cases of AIS, 76 cases of stage IA1 squamous cell carcinoma (SCC) and 27 cases of stage IA1 adenocarcinoma (ADC). A total of 88 (40.6%) patients had an intact uterus without radiotherapy. Five patients experienced HSIL+ recurrence. The cumulative 3-, 5- and 10-year incidence rates of HSILs + were 1.0%, 1.5% and 2.0%, respectively. No significant risk factors, including primary disease, margin status and hysterectomy, were associated with recurrence. Twenty (66.7%) of 30 patients who attempted pregnancy had 23 successful pregnancies, which result in 7 miscarriages, 16 live births and 5 preterm births. Age at conization was the only independent risk factor associated with pregnancy, live births and preterm births. In conclusion, conization is safe for young women with AIS, stage IA1 SCC and ADC who desire future fertility, and the associated HSIL recurrence rate is low. Increased age significantly lowered the conception or live birth rate.
Geometry influences inflammatory host cell response and remodeling in tissue-engineered heart valves in-vivo
Authors: Motta Sarah E. , Fioretta Emanuela S. , Lintas Valentina , Dijkman Petra E. , Hilbe Monika , Frese Laura , Cesarovic Nikola , Loerakker Sandra , Baaijens Frank P. T. , Falk Volkmar , Hoerstrup Simon P. , Emmert Maximilian Y.
Published: November 2020

Regenerative tissue-engineered matrix-based heart valves (TEM-based TEHVs) may become an alternative to currently-used bioprostheses for transcatheter valve replacement. We recently identified TEM-based TEHVs-geometry as one key-factor guiding their remodeling towards successful long-term performance or failure. While our first-generation TEHVs, with a simple, non-physiological valve-geometry, failed over time due to leaflet-wall fusion phenomena, our second-generation TEHVs, with a computational modeling-inspired design, showed native-like remodeling resulting in long-term performance. However, a thorough understanding on how TEHV-geometry impacts the underlying host cell response, which in return determines tissue remodeling, is not yet fully understood. To assess that, we here present a comparative samples evaluation derived from our first- and second-generation TEHVs. We performed an in-depth qualitative and quantitative (immuno-)histological analysis focusing on key-players of the inflammatory and remodeling cascades (M1/M2 macrophages, α-SMA+- and endothelial cells). First-generation TEHVs were prone to chronic inflammation, showing a high presence of macrophages and α-SMA+-cells, hinge-area thickening, and delayed endothelialization. Second-generation TEHVs presented with negligible amounts of macrophages and α-SMA+-cells, absence of hinge-area thickening, and early endothelialization. Our results suggest that TEHV-geometry can significantly influence the host cell response by determining the infiltration and presence of macrophages and α-SMA+-cells, which play a crucial role in orchestrating TEHV remodeling.
Intact in vivo visualization of telencephalic microvasculature in medaka using optical coherence tomography
Authors: Suzuki Takashi , Ueno Tomohiro , Oishi Naoya , Fukuyama Hidenao
Published: November 2020

To date, various human disease models in small fish—such as medaka (Oryzias lapties)—have been developed for medical and pharmacological studies. Although genetic and environmental homogeneities exist, disease progressions can show large individual differences in animal models. In this study, we established an intact in vivo angiographic approach and explored vascular networks in the telencephalon of wild-type adult medaka using the spectral-domain optical coherence tomography. Our approach, which required neither surgical operations nor labeling agents, allowed to visualize blood vessels in medaka telencephala as small as about 8 µm, that is, almost the size of the blood cells of medaka. Besides, we could show the three-dimensional microvascular distribution in the medaka telencephalon. Therefore, the intact in vivo imaging via optical coherence tomography can be used to perform follow-up studies on cerebrovascular alterations in metabolic syndrome and their associations with neurodegenerative disease models in medaka.
Fungus-originated genes in the genomes of cereal and pasture grasses acquired through ancient lateral transfer
Authors: Shinozuka Hiroshi , Shinozuka Maiko , de Vries Ellen M. , Sawbridge Timothy I. , Spangenberg German C. , Cocks Benjamin G.
Published: November 2020

Evidence for ancestral gene transfer between Epichloë fungal endophyte ancestors and their host grass species is described. From genomes of cool-season grasses (the Poeae tribe), two Epichloë-originated genes were identified through DNA sequence similarity analysis. The two genes showed 96% and 85% DNA sequence identities between the corresponding Epichloë genes. One of the genes was specific to the Loliinae sub-tribe. The other gene was more widely conserved in the Poeae and Triticeae tribes, including wheat (Triticum aestivum L.) and barley (Hordeum vulgare L.). The genes were independently transferred during the last 39 million years. The transferred genes were expressed in plant tissues, presumably retaining molecular functions. Multiple gene transfer events between the specific plant and fungal lineages are unique. A range of cereal crops is included in the Poeae and Triticeae tribes, and the Loliinae sub-tribe is consisted of economically important pasture and forage crops. Identification and characterisation of the 'natural' adaptation transgenes in the genomes of cereals, and pasture and forage grasses, that worldwide underpin the production of major foods, such as bread, meat, and milk, may change the ‘unnatural’ perception status of transgenic and gene-edited plants.
Towards image-based cancer cell lines authentication using deep neural networks
Authors: Mzurikwao Deogratias , Khan Muhammad Usman , Samuel Oluwarotimi Williams , Cinatl Jindrich , Wass Mark , Michaelis Martin , Marcelli Gianluca , Ang Chee Siang
Published: November 2020

Although short tandem repeat (STR) analysis is available as a reliable method for the determination of the genetic origin of cell lines, the occurrence of misauthenticated cell lines remains an important issue. Reasons include the cost, effort and time associated with STR analysis. Moreover, there are currently no methods for the discrimination between isogenic cell lines (cell lines of the same genetic origin, e.g. different cell lines derived from the same organism, clonal sublines, sublines adapted to grow under certain conditions). Hence, additional complementary, ideally low-cost and low-effort methods are required that enable (1) the monitoring of cell line identity as part of the daily laboratory routine and 2) the authentication of isogenic cell lines. In this research, we automate the process of cell line identification by image-based analysis using deep convolutional neural networks. Two different convolutional neural networks models (MobileNet and InceptionResNet V2) were trained to automatically identify four parental cancer cell line (COLO 704, EFO-21, EFO-27 and UKF-NB-3) and their sublines adapted to the anti-cancer drugs cisplatin (COLO-704rCDDP1000, EFO-21rCDDP2000, EFO-27rCDDP2000) or oxaliplatin (UKF-NB-3rOXALI2000), hence resulting in an eight-class problem. Our best performing model, InceptionResNet V2, achieved an average of 0.91 F1-score on tenfold cross validation with an average area under the curve (AUC) of 0.95, for the 8-class problem. Our best model also achieved an average F1-score of 0.94 and 0.96 on the authentication through a classification process of the four parental cell lines and the respective drug-adapted cells, respectively, on a four-class problem separately. These findings provide the basis for further development of the application of deep learning for the automation of cell line authentication into a readily available easy-to-use methodology that enables routine monitoring of the identity of cell lines including isogenic cell lines. It should be noted that, this is just a proof of principal that, images can also be used as a method for authentication of cancer cell lines and not a replacement for the STR method.
Rotation-time symmetry in bosonic systems and the existence of exceptional points in the absence of $${\mathscr{PT}}$$ symmetry
Authors: Lange Ewelina , Chimczak Grzegorz , Kowalewska-Kudłaszyk Anna , Bartkiewicz Karol
Published: November 2020

We study symmetries of open bosonic systems in the presence of laser pumping. Non-Hermitian Hamiltonians describing these systems can be parity-time ($${{\mathscr{PT}}}$$PT) symmetric in special cases only. Systems exhibiting this symmetry are characterised by real-valued energy spectra and can display exceptional points, where a symmetry-breaking transition occurs. We demonstrate that there is a more general type of symmetry, i.e., rotation-time ($${\mathscr{RT}}$$RT) symmetry. We observe that$${\mathscr{RT}}$$RT-symmetric non-Hermitian Hamiltonians exhibit real-valued energy spectra which can be made singular by symmetry breaking. To calculate the spectra of the studied bosonic non-diagonalisable Hamiltonians we apply diagonalisation methods based on bosonic algebra. Finally, we list a versatile set rules allowing to immediately identifying or constructing$${\mathscr{RT}}$$RT-symmetric Hamiltonians. We believe that our results on the$${\mathscr{RT}}$$RT-symmetric class of bosonic systems and their spectral singularities can lead to new applications inspired by those of the$${{\mathscr{PT}}}$$PT-symmetric systems.
New criteria for efficient Raman and Brillouin amplification of laser beams in plasma
Authors: Trines R. M. G. M. , Alves E. P. , Webb E. , Vieira J. , Fiúza F. , Fonseca R. A. , Silva L. O. , Cairns R. A. , Bingham R.
Published: November 2020

Raman or Brillouin amplification of a laser beam in plasma has long been seen as a way to reach multi-PW powers in compact laser systems. However, no significant plasma-based Raman amplification of a laser pulse beyond 0.1 TW has been achieved in nearly 20 years, and only one report of Brillouin amplification beyond 1 TW. In this paper, we reveal novel non-linear criteria for the initial seed pulse that will finally open the door to efficient Raman and Brillouin amplification to petawatt powers and Joule-level energies. We show that the triple product of the coupling constant $$\Gamma $$
Γ
, seed pulse duration $$\tau $$
τ
and seed pulse amplitude a for the Raman seed pulse (or $$a^{2/3}$$

a

2
/
3

for Brillouin) must exceed a specific minimum threshold for efficient amplification. We also analyze the plasma-based Raman and Brillouin amplification experiments to date, and show that the seed pulses used in nearly all experiments are well below our new threshold, which explains the poor efficiency obtained in them. Finally, we analyze a recent Brillouin amplification experiment that used increased seed pulse power to obtain Joule-level amplification, and find excellent agreement with our theory.
Dynamic regulation of coral energy metabolism throughout the diel cycle
Authors: Linsmayer Lauren Buckley , Deheyn Dimitri Dominique , Tomanek Lars , Tresguerres Martin
Published: November 2020

Coral reefs are naturally exposed to daily and seasonal variations in environmental oxygen levels, which can be exacerbated in intensity and duration by anthropogenic activities. However, coral’s diel oxygen dynamics and fermentative pathways remain poorly understood. Here, continuous oxygen microelectrode recordings in the coral diffusive boundary layer revealed hyperoxia during daytime and hypoxia at nighttime resulting from net photosynthesis and net respiration, respectively. The activities of the metabolic enzymes citrate synthase (CS), malate dehydrogenase, and strombine dehydrogenase remained constant throughout the day/night cycle, suggesting that energy metabolism was regulated through adjustments in metabolite fluxes and not through changes in enzyme abundance. Liquid chromatography-mass spectrometry analyses identified strombine as coral’s main fermentative end product. Strombine levels peaked as oxygen became depleted at dusk, indicating increased fermentation rates at the onset of nightly hypoxia, and again at dawn as photosynthesis restored oxygen and photosynthate supply. When these peaks were excluded from the analyses, average strombine levels during the day were nearly double those at night, indicating sifnificant fermentation rates even during aerobic conditions. These results highlight the dynamic changes in oxygen levels in the coral diffusive boundary layer, and the importance of fermentative metabolism for coral biology.
Association between maternal blood lipids levels during pregnancy and risk of small-for-gestational-age infants
Authors: Chen Qinqing , Chen Huiqi , Xi Fangfang , Sagnelli Matthew , Zhao Baihui , Chen Yuan , Yang Mengmeng , Xu Dong , Jiang Ying , Chen Guangdi , Luo Qiong
Published: November 2020

Dyslipidemia in pregnancy are associated with risk of adverse outcomes. As an adverse pregnancy outcome, small-for-gestational-age has been extensively studied in Western countries. However, similar studies have rarely been conducted in Asian countries. Data were derived from 5695 pairs of non-diabetic mothers and neonates between 1 Jan 2014 and 31 Dec 2014. 5.6% neonates in our study were SGA. Serum samples were collected during second and third trimesters for evaluation on fasting lipids levels. The present study intended to explore the associations between maternal lipid profile and small-for-gestational-age neonates. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated and adjusted via logistic regression analysis. After adjustments for confounders, third-trimester total cholesterol levels were associated with a decreased risk for small-for-gestational-age (aOR = 0.622, 95% CI 0.458–0.848, P = 0.002), and third-trimester high-density lipoprotein cholesterol and low-density lipoprotein cholesterol levels were associated with an increased risk for small-for-gestational-age (aOR = 1.955, 95% CI 1.465–2.578, P < 0.001; aOR = 1.403, 95% CI 1.014–1.944, P = 0.041).In the highest gestational weight gain strata, especially the third-trimester, the effect of high-density lipoprotein cholesterol levels on the risk for small-for-gestational-age is larger. High high-density lipoprotein cholesterol level during third trimester could be considered as indicators of a high-risk of small-for-gestational-age, regardless of gestational weight gain.
APOE4 genetic polymorphism results in impaired recovery in a repeated mild traumatic brain injury model and treatment with Bryostatin-1 improves outcomes
Authors: Giarratana Anna O. , Zheng Cynthia , Reddi Sahithi , Teng Shavonne L. , Berger David , Adler Derek , Sullivan Patrick , Thakker-Varia Smita , Alder Janet
Published: November 2020

After traumatic brain injury (TBI), some people have worse recovery than others. Single nucleotide polymorphisms (SNPs) in Apolipoprotein E (APOE) are known to increase risk for developing Alzheimer’s disease, however there is controversy from human and rodent studies as to whether ApoE4 is a risk factor for worse outcomes after brain trauma. To resolve these conflicting studies we have explored the effect of the human APOE4 gene in a reproducible mouse model that mimics common human injuries. We have investigated cellular and behavioral outcomes in genetically engineered human APOE targeted replacement (TR) mice following repeated mild TBI (rmTBI) using a lateral fluid percussion injury model. Relative to injured APOE3 TR mice, injured APOE4 TR mice had more inflammation, neurodegeneration, apoptosis, p-tau, and activated microglia and less total brain-derived neurotrophic factor (BDNF) in the cortex and/or hippocampus at 1 and/or 21 days post-injury. We utilized a novel personalized approach to treating APOE4 susceptible mice by administering Bryostatin-1, which improved cellular as well as motor and cognitive behavior outcomes at 1 DPI in the APOE4 injured mice. This study demonstrates that APOE4 is a risk factor for poor outcomes after rmTBI and highlights how personalized therapeutics can be a powerful treatment option.
Exposure to a biopesticide interferes with sucrose responsiveness and learning in honey bees
Authors: Carlesso Daniele , Smargiassi Stefania , Sassoli Lara , Cappa Federico , Cervo Rita , Baracchi David
Published: November 2020

The entomopathogenic fungus Beauveriabassiana is a widely used biopesticide that is considered as an effective alternative to classical agrochemicals. B. bassiana is thought to be safe for pollinators although little is known about its side-effects on pollinators’ behaviour and cognition. Here, we focused on honey bees and used the proboscis extension response (PER) protocol to assess whether B. bassiana affects individual sucrose responsiveness, non-associative and associative olfactory learning and memory. Fungus-treated bees displayed an enhanced sucrose responsiveness, which could not be explained by metabolic alterations. Strikingly, exposed bees were twice as inconsistent as controls in response to sucrose, showing PER to lower but not to higher sucrose concentrations. Exposed bees habituated less to sucrose and had a better acquisition performance in the conditioning phase than controls. Further, neither mid- nor long-term memory were affected by the fungus. As sucrose responsiveness is the main determinant of division of foraging labour, these changes might unsettle the numerical ratio between the sub-castes of foragers leading to suboptimal foraging. Although the use of biocontrol strategies should be preferred over chemical pesticides, careful assessment of their side-effects is crucial before claiming that they are safe for pollinators.
Tree canopy arthropods have idiosyncratic responses to plant ecophysiological traits in a warm temperate forest complex
Authors: Swart Rudi C. , Samways Michael J. , Roets Francois
Published: November 2020

Biodiversity studies on forest canopies often have narrow arthropod taxonomic focus, or refer to a single species of tree. In response, and to better understand the wide range of drivers of arthropod diversity in tree canopies, we conducted a large-scale, multi-taxon study which (a) included effect of immediate surroundings of an individual tree on plant physiological features, and (b), how these features affect compositional and functional arthropod diversity, in a warm, southern Afro-temperate forest. We found that tree species differed significantly in plant physiological features and arthropod diversity patterns. Surprisingly, we found negative correlation between surrounding canopy cover, and both foliar carbon and arthropod diversity in host trees, regardless of tree species. Subtle, tree intraspecific variation in physiological features correlated significantly with arthropod diversity measures, but direction and strength of correlations differed among tree species. These findings illustrate great complexity in how canopy arthropods respond to specific tree species, to immediate surroundings of host trees, and to tree physiological features. We conclude that in natural forests, loss of even one tree species, as well as homogenization of the crown layer and/or human-induced environmental change, could lead to profound and unpredictable canopy arthropod biodiversity responses, threatening forest integrity.
The importance of using whole genome sequencing and extended spectrum beta-lactamase selective media when monitoring antimicrobial resistance
Authors: Duggett Nicholas , AbuOun Manal , Randall Luke , Horton Robert , Lemma Fabrizio , Rogers Jon , Crook Derrick , Teale Christopher , Anjum Muna F.
Published: November 2020

To tackle the problem of antimicrobial resistance (AMR) surveillance programmes are in place within Europe applying phenotypic methods, but there are plans for implementing whole genome sequencing (WGS). We tested the benefits of WGS using Escherichia coli collected from pig surveillance performed between 2013 to 2017. WGS was performed on 498 E. coli producing ESBL and AmpC enzymes, recovered from pig caeca on MacConkey + cefotaxime (McC + CTX) agar, as recommended by the European Commission, or ESBL agar, used additionally by United Kingdom. Our results indicated WGS was extremely useful for monitoring trends for specific ESBL genes, as well as a plethora of AMR genotypes, helping to establish their prevalence and co-linkage to certain plasmids. Recovery of isolates with multi-drug resistance (MDR) genotypes was lower from McC + CTX than ESBL agar. The most widespread ESBL genes belonged to the blaCTX-M family. blaCTX-M-1 dominated all years, and was common in two highly stable IncI1 MDR plasmids harbouring (blaCTX-M-1,sul2, tetA) or (blaCTX-M-1, aadA5, sul2, dfrA17), in isolates which were phylogenetically dissimilar, suggesting plasmid transmission. Therefore, WGS provided a wealth of data on prevalence of AMR genotypes and plasmid persistence absent from phenotypic data and, also, demonstrated the importance of culture media for detecting ESBL E. coli.
Development and validation of a 4-color multiplexing spinal muscular atrophy (SMA) genotyping assay on a novel integrated digital PCR instrument
Authors: Jiang Lingxia , Lin Robert , Gallagher Steve , Zayac Andrew , Butchbach Matthew E. R. , Hung Paul
Published: November 2020

Digital PCR (dPCR) technology has been proven to be highly sensitive and accurate in detecting copy number variations (CNV). However, a higher-order multiplexing dPCR assay for measuring SMN1 and SMN2 copy numbers in spinal muscular atrophy (SMA) samples has not been reported. Described here is a rapid multiplex SMA dPCR genotyping assay run on a fully integrated dPCR instrument with five optical channels. The hydrolysis probe-based multiplex dPCR assay quantifies SMN1, SMN2, and the total SMN (SMN1 + SMN2) while using RPPH1 gene as an internal reference control. The quadruplex assay was evaluated with characterized control DNA samples and validated with 15 blinded clinical samples from a previously published study. SMN1 and SMN2 copy numbers were completely concordant with previous results for both the control and blinded samples. The dPCR-based SMA copy number determination was accomplished in 90 min with a walk-away workflow identical to real-time quantitative PCR (qPCR). In summary, presented here is a simple higher-order multiplexing solution on a novel digital PCR platform to meet the growing demand for SMA genotyping and prognostics.
Implications of landscape genetics and connectivity of snow leopard in the Nepalese Himalayas for its conservation
Authors: Shrestha Bikram , Kindlmann Pavel
Published: November 2020

The snow leopard is one of the most endangered large mammals. Its population, already low, is declining, most likely due to the consequences of human activity, including a reduction in the size and number of suitable habitats. With climate change, habitat loss may escalate, because of an upward shift in the tree line and concomitant loss of the alpine zone, where the snow leopard lives. Migration between suitable areas, therefore, is important because a decline in abundance in these areas may result in inbreeding, fragmentation of populations, reduction in genetic variation due to habitat fragmentation, loss of connectivity, bottlenecks or genetic drift. Here we use our data collected in Nepal to determine the areas suitable for snow leopards, by using habitat suitability maps, and describe the genetic structure of the snow leopard within and between these areas. We also determine the influence of landscape features on the genetic structure of its populations and reveal corridors connecting suitable areas. We conclude that it is necessary to protect these natural corridors to maintain the possibility of snow leopards’ migration between suitable areas, which will enable gene flow between the diminishing populations and thus maintain a viable metapopulation of snow leopards.
Neuronal architecture of the second-order CO2 pathway in the brain of a noctuid moth
Authors: Chu X. , KC P. , Ian E. , Kvello P. , Liu Y. , Wang G. R. , Berg B. G.
Published: November 2020

Many insects possess the ability to detect fine fluctuations in the environmental CO2 concentration. In herbivorous species, plant-emitted CO2, in combination with other sensory cues, affect many behaviors including foraging and oviposition. In contrast to the comprehensive knowledge obtained on the insect olfactory pathway in recent years, we still know little about the central CO2 system. By utilizing intracellular labeling and mass staining, we report the neuroanatomy of projection neurons connected with the CO2 sensitive antennal-lobe glomerulus, the labial pit organ glomerulus (LPOG), in the noctuid moth, Helicoverpa armigera. We identified 15 individual LPOG projection neurons passing along different tracts. Most of these uniglomerular neurons terminated in the lateral horn, a previously well-described target area of plant-odor projection neurons originating from the numerous ordinary antennal-lobe glomeruli. The other higher-order processing area for odor information, the calyces, on the other hand, was weakly innervated by the LPOG neurons. The overlapping LPOG terminals in the lateral horn, which is considered important for innate behavior in insects, suggests the biological importance of integrating the CO2 input with plant odor information while the weak innervation of the calyces indicates the insignificance of this ubiquitous cue for learning mechanisms.
Climatic factors determine the yield and quality of Honghe flue-cured tobacco
Authors: Tang Zuoxin , Chen Lulu , Chen Zebin , Fu Yali , Sun Xiaolu , Wang Binbin , Xia Tiyuan
Published: November 2020

Flue-cured tobacco (Nicotiana tabacum L.) is a major cash crop in Yunnan, China, and the yield, chemical components, and their proportions decide the quality of tobacco leaves. To understand the effects of environmental factors (soil and climatic factors) on the yield and quality of flue-cured tobacco and determine the main regulating factors, we selected three flue-cured tobacco cultivars [K326, Yunyan87 (Yun87), and Honghuadajinyuan (Hongda)] grown in the Honghe Tobacco Zone. Indices related to yield and economic traits, chemical component properties, soil physical and chemical properties, and climatic factors at different planting sites, were evaluated. We used variance analysis, correlation analysis, and redundancy analysis (RDA) in this study. The results showed that the yield and chemical component properties of flue-cured tobacco, except for the number of left leaves and plant total sugar (PTS) content, were significantly correlated with climatic factors. Particularly, the yield increased in drier and sunnier weather. In terms of the carbon supply capacity, PTS, petroleum ether (PPE), and starch contents (PS) were higher under high-altitude and high-latitude climatic conditions, whereas for the nitrogen supply capacity, plant nitrogen (PTN) and nicotine (PN) contents improved under low-altitude and low-latitude climatic conditions. PTS, reducing sugar (PRS), potassium (PTK), chlorine (PCL), and PPE contents were negatively related to soil clay content, soil pH, and soil organic matter, whereas PRS and PTK contents were positively correlated with alkali-hydrolyzed nitrogen (AN). According to RDA, the soil clay, AN, available phosphorus (AP), and soil chlorine content (SCL) strongly affected the quality of flue-cured tobacco. The quality of the K326 and Yun87 cultivars was mostly influenced by moisture, whereas the quality of the Hongda cultivar was mostly affected by temperature. In conclusion, compared with soil properties, climatic factors more significantly affect the yield and quality of Honghe flue-cured tobacco leaves.
External error attribution dampens efferent-based predictions but not proprioceptive changes in hand localization
Authors: Gastrock Raphael Q. , Modchalingam Shanaathanan , ’t Hart Bernard Marius , Henriques Denise Y. P.
Published: November 2020

In learning and adapting movements in changing conditions, people attribute the errors they experience to a combined weighting of internal or external sources. As such, error attribution that places more weight on external sources should lead to decreased updates in our internal models for movement of the limb or estimating the position of the effector, i.e. there should be reduced implicit learning. However, measures of implicit learning are the same whether or not we induce explicit adaptation with instructions about the nature of the perturbation. Here we evoke clearly external errors by either demonstrating the rotation on every trial, or showing the hand itself throughout training. Implicit reach aftereffects persist, but are reduced in both groups. Only for the group viewing the hand, changes in hand position estimates suggest that predicted sensory consequences are not updated, but only rely on recalibrated proprioception. Our results show that estimating the position of the hand incorporates source attribution during motor learning, but recalibrated proprioception is an implicit process unaffected by external error attribution.
Extremely hard and tough high entropy nitride ceramics
Authors: Moskovskikh Dmitry , Vorotilo Stepan , Buinevich Veronika , Sedegov Alexey , Kuskov Kirill , Khort Alexander , Shuck Christopher , Zhukovskyi Maksim , Mukasyan Alexander
Published: November 2020

Simultaneously hard and tough nitride ceramics open new venues for a variety of advanced applications. To produce such materials, attention is focused on the development of high-entropy ceramics, containing four or more metallic components distributed homogeneously in the metallic sublattice. While the fabrication of bulk high-entropy carbides and borides is well established, high-entropy nitrides have only been produced as thin films. Herein, we report on a newel three-step process to fabricate bulk high-entropy nitrides. The high-entropy nitride phase was obtained by exothermic combustion of mechanically-activated nanostructured metallic precursors in nitrogen and consolidated by spark plasma sintering. The fabricated bulk high-entropy nitride (Hf0.2Nb0.2Ta0.2Ti0.2Zr0.2)N demonstrates outstanding hardness (up to 33 GPa) and fracture toughness (up to 5.2 MPa∙m1/2), significantly surpassing expected values from mixture rules, as well as all other reported binary and high-entropy ceramics and can be used for super-hard coatings, structural materials, optics, and others. The obtained results illustrate the scalable method to produce bulk high-entropy nitrides with the new benchmark properties.
Tetrahydrobiopterin prevents chronic ischemia-related lower urinary tract dysfunction through the maintenance of nitric oxide bioavailability
Authors: Akaihata Hidenori , Hata Junya , Tanji Ryo , Honda-Takinami Ruriko , Matsuoka Kanako , Sato Yuichi , Kataoka Masao , Ogawa Soichiro , Kojima Yoshiyuki
Published: November 2020

This study aimed to investigate the influence of chronic ischemia on nitric oxide biosynthesis in the bladder and the effect of administering tetrahydrobiopterin (BH4), a cofactor for endothelial nitric oxide synthase (eNOS), on chronic ischemia-related lower urinary tract dysfunction (LUTD). This study divided male Sprague–Dawley rats into Control, chronic bladder ischemia (CBI) and CBI with oral BH4 supplementation (CBI/BH4) groups. In the CBI group, bladder capacity and bladder muscle strip contractility were significantly lower, and arterial wall was significantly thicker than in Controls. Significant improvements were seen in bladder capacity, muscle strip contractility and arterial wall thickening in the CBI/BH4 group as compared with the CBI group. Western blot analysis of bladder showed expressions of eNOS (p = 0.043), HIF-1α (p < 0.01) and dihydrofolate reductase (DHFR) (p < 0.01), which could regenerate BH4, were significantly higher in the CBI group than in Controls. In the CBI/BH4 group, HIF-1α (p = 0.012) and DHFR expressions (p = 0.018) were significantly decreased compared with the CBI group. Our results suggest that chronic ischemia increases eNOS and DHFR in the bladder to prevent atherosclerosis progression. However, DHFR could not synthesize sufficient BH4 relative to the increased eNOS, resulting in LUTD. BH4 supplementation protects lower urinary tract function by promoting eNOS activity.
Metabolic interaction between amino acid deprivation and cisplatin synergistically reduces phosphoribosyl-pyrophosphate and augments cisplatin cytotoxicity
Authors: Wahwah Nisreen , Dhar Debanjan , Chen Hui , Zhuang Shunhui , Chan Adriano , Casteel Darren E. , Kalyanaraman Hema , Pilz Renate B. , Boss Gerry R.
Published: November 2020

Cisplatin is a mainstay of cancer chemotherapy. It forms DNA adducts, thereby activating poly(ADP-ribose) polymerases (PARPs) to initiate DNA repair. The PARP substrate NAD+ is synthesized from 5-phosphoribose-1-pyrophosphate (PRPP), and we found that treating cells for 6 h with cisplatin reduced intracellular PRPP availability. The decrease in PRPP was likely from (1) increased PRPP consumption, because cisplatin increased protein PARylation and PARP1 shRNA knock-down returned PRPP towards normal, and (2) decreased intracellular phosphate, which down-regulated PRPP synthetase activity. Depriving cells of a single essential amino acid decreased PRPP synthetase activity with a half-life of ~ 8 h, and combining cisplatin and amino acid deprivation synergistically reduced intracellular PRPP. PRPP is a rate-limiting substrate for purine nucleotide synthesis, and cisplatin inhibited de novo purine synthesis and DNA synthesis, with amino acid deprivation augmenting cisplatin’s effects. Amino acid deprivation enhanced cisplatin’s cytotoxicity, increasing cellular apoptosis and DNA strand breaks in vitro, and intermittent deprivation of lysine combined with a sub-therapeutic dose of cisplatin inhibited growth of ectopic hepatomas in mice. Augmentation of cisplatin’s biochemical and cytotoxic effects by amino acid deprivation suggest that intermittent deprivation of an essential amino acid could allow dose reduction of cisplatin; this could reduce the drug’s side effects, and allow its use in cisplatin-resistant tumors.
The architecture of corneal stromal striae on optical coherence tomography and histology in an animal model and in humans
Authors: Napoli Pietro Emanuele , Nioi Matteo , d’Aloja Ernesto , Loy Francesco , Fossarello Maurizio
Published: November 2020

The purpose of this study was to use a portable optical coherence tomography (OCT) for characterization of corneal stromal striae (CSS) in an ovine animal model and human corneas with histological correlation, in order to evaluate their architectural pattern by image analysis. Forty-six eyes from female adult sheep (older than 2 years), and 12 human corneas, were included in our study. The eyes were examined in situ by a portable OCT, without enucleation. All OCT scans were performed immediately after death, and then the eyes were delivered to a qualified histology laboratory. In the ovine animal model, CSS were detected with OCT in 89.1% (41/46) of individual scans and in 93.4% (43/46) of histological slices. In human corneas, CSS were found in 58.3% (7/12) of cases. In both corneal types, CSS appeared as “V”- or “X”-shaped structures, with very similar angle values of 70.8° ± 4° on OCT images and 71° ± 4° on histological slices (p ≤ 0.01). Data analysis demonstrated an excellent degree of reproducibility and inter-rater reliability of measurements (p < 0.001). The present study demonstrated that by using a portable OCT device, CSS can be visualized in ovine and human corneas. This finding suggests their generalized presence in various mammals. The frequent observation, close to 60%, of such collagen texture in the corneal stroma, similar to a ‘truss bridge’ design, permits to presume that it plays an important structural role, aimed to distribute tensile and compressive forces in various directions, conferring resilience properties to the cornea.
The power struggle: assessing interacting global change stressors via experimental studies on sharks
Authors: Bouyoucos Ian A. , Watson Sue-Ann , Planes Serge , Simpfendorfer Colin A. , Schwieterman Gail D. , Whitney Nicholas M. , Rummer Jodie L.
Published: November 2020

Ocean warming and acidification act concurrently on marine ectotherms with the potential for detrimental, synergistic effects; yet, effects of these stressors remain understudied in large predatory fishes, including sharks. We tested for behavioural and physiological responses of blacktip reef shark (Carcharhinus melanopterus) neonates to climate change relevant changes in temperature (28 and 31 °C) and carbon dioxide partial pressures (pCO2; 650 and 1050 µatm) using a fully factorial design. Behavioural assays (lateralisation, activity level) were conducted upon 7–13 days of acclimation, and physiological assays (hypoxia tolerance, oxygen uptake rates, acid–base and haematological status) were conducted upon 14–17 days of acclimation. Haematocrit was higher in sharks acclimated to 31 °C than to 28 °C. Significant treatment effects were also detected for blood lactate and minimum oxygen uptake rate; although, these observations were not supported by adequate statistical power. Inter-individual variability was considerable for all measured traits, except for haematocrit. Moving forward, studies on similarly ‘hard-to-study’ species may account for large inter-individual variability by increasing replication, testing larger, yet ecologically relevant, differences in temperature and pCO2, and reducing measurement error. Robust experimental studies on elasmobranchs are critical to meaningfully assess the threat of global change stressors in these data-deficient species.
Investigation of COSMO-SAC model for solubility and cocrystal formation of pharmaceutical compounds
Authors: Mahmoudabadi Samane Zarei , Pazuki Gholamreza
Published: November 2020

In this study, a predictive model named COSMO-SAC was investigated in solid/liquid equilibria for pharmaceutical compounds. The examined properties were the solubility of drug in the pure and mixed solvents, octanol/water partition coefficient, and cocrystal formation. The results of the original COSMO-SAC model (COSMO-SAC (2002)) was compared with a semi-predictive model named Flory–Huggins model and a revised version of the COSMO-SAC (COSMO-SAC (2010)). The results indicated the acceptable accuracy of the COSMO-SAC (2002) in the considered scope. The results emphasized on the suitability of the COSMO-SAC model for simple molecules containing C, H, and O by covalent and hydrogen bonding interactions. Applicability of the COSMO-SAC for more complicated molecules made of various functional groups such as COO and COOH doubly requires more modification in the COSMO-SAC.
Synthesis and initial screening of lactate dehydrogenase inhibitor activity of 1,3-benzodioxole derivatives
Authors: Annas Dicky , Cheon Se-Yun , Yusuf Mohammad , Bae Sung-Jin , Ha Ki-Tae , Park Kang Hyun
Published: November 2020

Cancer is one of the main causes of mortality in the world. Many cancer cells produce ATP through high-level lactic acid fermentation catalyzed by lactate dehydrogenase (LDH), which converts pyruvic acid to lactic acid. LDH plays a dominant role in the Warburg effect, wherein aerobic glycolysis is favored over oxidative phosphorylation. Due to the high lactic acid production level in cancer cells, LDH-targeting could be a potential cancer treatment strategy. A few approaches, such as drug treatment, reportedly inhibited LDH activity. In this study, we describe new 1,3-benzodioxole derivatives that might be potential small molecule candidates for LDHA inhibition. The synthesis was carried out by trans-esterification between aryl ester and alcohol groups from piperonyl alcohol. Compounds 2 and 10 exhibited a selective LDHA IC50 value of 13.63 µM and 47.2 µM, respectively. Whereas only compound 10 showed significant cytotoxicity in several lines of cancer cells, especially in human pancreatic cancer PANC-1 cells. These synthesized compounds possess 2 aromatic rings and –CF3 moiety, which expectedly contributes to LDHA inhibition. The presented products have the potential to become a promising LDHA inhibitor drug candidate.
Foveal crack sign as a predictive biomarker for development of macular hole in fellow eyes of patients with full-thickness macular holes
Authors: Furashova Olga , Matthé Egbert
Published: November 2020

To investigate the prevalence and predictive value of the foveal crack sign (FCS) in fellow eyes of patients with full-thickness macular holes (FTMH) regarding future macular hole (MH) formation. In a retrospective observational case series, 113 fellow eyes of 113 patients with FTMH have been observed during a mean follow-up time of 21 months. According to baseline SD-OCT images, patients were divided into 4 separate groups: patients with FCS and vitreous adhesion, patients with FCS and vitreous detachment, patients without FCS with vitreous adhesion, patients without FCS with vitreous detachment. Progression rate to MH formation, predictive value of FCS and of vitreous interface status were calculated and compared across the four groups. FCS was observed in 19 of 113 fellow eyes (17%) of patients with FTMH, 10 of them with progression to MH during the mean follow up time of 21 months. 2 other eyes with progression to MH showed no FCS at baseline. Progression rate was shown to be 77% (10 of 13 eyes) in patients with FCS and vitreous adhesion, 0% (none of 6 eyes) in patients with FCS and vitreous detachment, 4% (2 of 48 eyes) in patients without FCS with vitreous adhesion, 0% (none of 46 eyes) in patients without FCS with vitreous detachment. FCS had sensitivity of 83.3% (95% CI 50.9–97.1%) and specificity of 91.1% (95% CI 83.3–95.6%) in predicting MH formation, positive predictive value of FCS was 52.6% (95% CI 29.5–74.8%) and negative predictive value 97.9% (95% CI 91.8–99.6%). Having simultaneously FCS and vitreous adhesion showed 83.3% (95% CI 50.9–97.1%) sensitivity and 97.1% (95% CI 91.1–99.2%) specificity in predicting macular hole formation; positive predictive value was 76.9% (95% CI 46.0–93.8%) and negative predictive value was 98.0% (95% CI 92.4–99.7%). Fellow eyes of patients with FTMH with foveal crack sign are at a very high risk (77%) of FTMH development, as long as posterior vitreous adhesion is present.
New insights into quetiapine metabolism using molecular networking
Authors: Le Daré Brendan , Ferron Pierre-Jean , Allard Pierre-Marie , Clément Bruno , Morel Isabelle , Gicquel Thomas
Published: November 2020

Metabolism is involved in both pharmacology and toxicology of most xenobiotics including drugs. Yet, visualization tools facilitating metabolism exploration are still underused, despite the availibility of pertinent bioinformatics solutions. Since molecular networking appears as a suitable tool to explore structurally related molecules, we aimed to investigate its interest in in vitro metabolism exploration. Quetiapine, a widely prescribed antipsychotic drug, undergoes well-described extensive metabolism, and is therefore an ideal candidate for such a proof of concept. Quetiapine was incubated in metabolically competent human liver cell models (HepaRG) for different times (0 h, 3 h, 8 h, 24 h) with or without cytochrom P450 (CYP) inhibitor (ketoconazole as CYP3A4/5 inhibitor and quinidine as CYP2D6 inhibitor), in order to study its metabolism kinetic and pathways. HepaRG culture supernatants were analyzed on an ultra-high performance liquid chromatography coupled with tandem mass spectrometry (LC-HRMS/MS). Molecular networking approach on LC-HRMS/MS data allowed to quickly visualize the quetiapine metabolism kinetics and determine the major metabolic pathways (CYP3A4/5 and/or CYP2D6) involved in metabolite formation. In addition, two unknown putative metabolites have been detected. In vitro metabolite findings were confirmed in blood sample from a patient treated with quetiapine. This is the first report using LC-HRMS/MS untargeted screening and molecular networking to explore in vitro drug metabolism. Our data provide new evidences of the interest of molecular networking in drug metabolism exploration and allow our in vitro model consistency assessment.
Fabrication of a “turn-on”-type enantioselective fluorescence sensor via a modified achiral MOF: applications for synchronous detection of phenylalaninol enantiomers
Authors: Xiao Jiannan , Wang Xueling , Xu Xuebin , Tian Fuli , Liu Zhiliang
Published: November 2020

One pair of homochiral UiO-66 analogues, S-1 and R-1, can detect enantiomeric PA with different ef values and a distinct enantioselectivity factor α.
FTIR combined with chemometric tools (fingerprinting spectroscopy) in comparison to HPLC: which strategy offers more opportunities as a green analytical chemistry technique for pharmaceutical analysis
Authors: Kelani Khadiga M. , Rezk Mamdouh R. , Monir Hany H. , ElSherbiny Menna S. , Eid Sherif M.
Published: November 2020

Herein, ATR-FTIR coupled to chemometrics was used to quantitatively determine active pharmaceutical ingredient combinations, and compared to the chromatographic techniques as HPLC on the light of the twelve principles of green analytical chemistry.
Oxidative addition of Bi–C bonds to Pt(0): reaction of Pt(PEt3)3 with cyclic organobismuth compounds
Authors: Shimada Shigeru , Wang Xiang-Bo , Tanaka Masato
Published: November 2020

Oxidative addition of a Bi–C bond to a transition metal complex was demonstrated for the first time.
Syntheses, formation mechanisms and structures of a series of linear diborazanes
Authors: Li Huizhen , Wang Ruirui , Kang Jiaxin , Li Shujun , Zhou Ai-Ju , Han Dong-xue , Guan Hong-Yu , Austin Douglas J. , Yue Yanfeng
Published: November 2020

Both anti and gauche conformations are observed in the linear diborazanes, which are stabilized by inter- and intramolecular DHBs, respectively.