bluuebunny/crossref_metadata_2025 huggingface dataset:
Parental effects via glyphosate-based herbicides in a bird model?
Authors: Ruuskanen Suvi , Rainio Miia , Uusitalo Maiju , Saikkonen Kari , Helander Marjo
Published: December 2019

Controversial glyphosate-based herbicides (GBHs) are the most frequently used herbicides across the globe. In an increasing number of studies, researchers have identified GBH residues in soil, water, crops, and food products exposing non-target organisms to health risks; these organisms include wildlife, livestock, and humans. However, GBH-related parental effects are poorly understood. In the case of birds, GBHs may be transferred directly from mother to developing offspring (i.e. direct effects) via eggs, or they may indirectly influence offspring performance by altered maternal condition or resource allocation to eggs, for example. We experimentally exposed a parental generation of Japanese quails (Coturnix japonica) to GBHs or respective controls, recorded egg quality and glyphosate residues in eggs, and studied embryonic development and oxidative biomarkers. Glyphosate accumulated in eggs (ca 0.76 kg/mg). Embryonic development tended to be lower in eggs of GBH-exposed parents compared to control parents. Embryonic brain tissue from GBH-exposed parents tended to express more lipid damage. Given that we detected no differences in egg quality (egg, yolk, or shell mass, or egg hormone concentration) across the treatment groups, our results suggest these are likely direct effects of GBHs on offspring rather than indirect effects via altered maternal allocation of resources or hormonal signals.

Capsule

Experimental, long-term parental exposure to GBHs tends to hinder offspring embryonic development and increase embryonic oxidative damage to lipids in a bird model.
Towards a digital diatom: image processing and deep learning analysis ofBacillaria paradoxadynamic morphology
Authors: Alicea Bradly , Gordon Richard , Harbich Thomas , Singh Ujjwal , Singh Asmit , Varma Vinay
Published: December 2019

Recent years have witnessed a convergence of data and methods that allow us to approximate the shape, size, and functional attributes of biological organisms. This is not only limited to traditional model species: given the ability to culture and visualize a specific organism, we can capture both its structural and functional attributes. We present a quantitative model for the colonial diatomBacillaria paradoxa, an organism that presents a number of unique attributes in terms of form and function. To acquire a digital model ofB. paradoxa, we extract a series of quantitative parameters from microscopy videos from both primary and secondary sources. These data are then analyzed using a variety of techniques, including two rival deep learning approaches. We provide an overview of neural networks for non-specialists as well as present a series of analysis onBacillariaphenotype data. The application of deep learning networks allows for two analytical purposes. Application of the DeepLabv3 pre-trained model extracts phenotypic parameters describing the shape of cells constitutingBacillariacolonies. Application of a semantic model trained on nematode embryogenesis data (OpenDevoCell) provides a means to analyze masked images of potential intracellular features. We also advance the analysis ofBacillariacolony movement dynamics by using templating techniques and biomechanical analysis to better understand the movement of individual cells relative to an entire colony. The broader implications of these results are presented, with an eye towards future applications to both hypothesis-driven studies and theoretical advancements in understanding the dynamic morphology ofBacillaria.
Longitudinal linked read sequencing reveals ecological and evolutionary responses of a human gut microbiome during antibiotic treatment
Authors: Roodgar Morteza , Good Benjamin H. , Garud Nandita R. , Martis Stephen , Avula Mohan , Zhou Wenyu , Lancaster Samuel M. , Lee Hayan , Babveyh Afshin , Nesamoney Sophia , Pollard Katherine S. , Snyder Michael P.
Published: December 2019

Gut microbial communities can respond to antibiotic perturbations by rapidly altering their taxonomic and functional composition. However, little is known about the strain-level processes that drive this collective response. Here we characterize the gut microbiome of a single individual at high temporal and genetic resolution through a period of health, disease, antibiotic treatment, and recovery. We used deep, linked-read metagenomic sequencing to track the longitudinal trajectories of thousands of single nucleotide variants within 36 species, which allowed us to contrast these genetic dynamics with the ecological fluctuations at the species level. We found that antibiotics can drive rapid shifts in the genetic composition of individual species, often involving incomplete genome-wide sweeps of pre-existing variants. These genetic changes were frequently observed in species without obvious changes in species abundance, emphasizing the importance of monitoring diversity below the species level. We also found that many sweeping variants quickly reverted to their baseline levels once antibiotic treatment had concluded, demonstrating that the ecological resilience of the microbiota can sometimes extend all the way down to the genetic level. Our results provide new insights into the population genetic forces that shape individual microbiomes on therapeutically relevant timescales, with potential implications for personalized health and disease.
Chromosome-level quality scaffolding of brown algal genomes using InstaGRAAL, a proximity ligation-based scaffolder
Authors: Baudry Lyam , Marbouty Martial , Marie-Nelly Hervé , Cormier Alexandre , Guiglielmoni Nadège , Avia Komlan , Mie Yann Loe , Godfroy Olivier , Sterck Lieven , Cock J. Mark , Zimmer Christophe , Coelho Susana M. , Koszul Romain
Published: December 2019

Hi-C has become a popular technique in recent genome assembly projects. Hi-C exploits contact frequencies between pairs of loci to bridge and order contigs in draft genomes, resulting in chromosome-level assemblies. However, application of this approach is currently hampered by a lack of robust programs that are capable of effectively treating this type of data, particularly open source programs. We developed instaGRAAL, a complete overhaul of the GRAAL program, which has adapted the latter to allow efficient assembly of large genomes. Both GRAAL, and instaGRAAL use a Markov Chain Monte Carlo algorithm to perform Hi-C scaffolding, but instaGRAAL features a number of improvements including a modular polishing approach that optionally integrates independent data. To validate the program, we used it to generate chromosome-level assemblies for two brown algae, Desmarestia herbacea and the model Ectocarpus sp., and quantified improvements compared to the initial draft for the latter. Overall, instaGRAAL is a program able to generate, using default parameters with minimal human intervention, near-complete assemblies.
MRI tracking reveals selective accumulation of stem cell-derived magneto-extracellular vesicles in sites of injury
Authors: Han Zheng , Liu Senquan , Pei Yigang , Ding Zheng , Li Yuguo , Weiss Robert G. , van Zijl Peter C.M. , Bulte Jeff W.M. , Cheng Linzhao , Liu Guanshu
Published: December 2019

Human stem-cell-derived extracellular vesicles (EVs) are currently being investigated for cell-free therapy in regenerative medicine applications, but their biodistribution and tropic properties for homing to injured tissues are largely unknown. Here, we labeled EVs with magnetic nanoparticles to create magneto-EVs that can be tracked by magnetic resonance imaging (MRI). Superparamagnetic iron oxide (SPIO) nanoparticles were coated with polyhistidine tags, which enabled purification of labeled EVs by efficiently removing unencapsulated SPIO particles in the solution. The biodistribution of systemically injected human induced pluripotent stem cell (iPSC)-derived magneto-EV was assessed in three different animal models of kidney injury and myocardial ischemia. Magneto-EVs were found to selectively home to the injury sites and conferred substantial protection in a kidney injury model.In vivoMRI tracking of magnetically labeled EVs represents a new powerful method to assess and quantify their whole-body distribution, which may help optimize further development of EV-based cell-free therapy.
Inhibiting xCT/SLC7A11 induces ferroptosis of myofibroblastic hepatic stellate cells and protects against liver fibrosis
Authors: Du Kuo , Oh Seh Hoon , Sun Tianai , Yang Wen-Hsuan , Chi Jen-Tsan Ashley , Diehl Anna Mae
Published: December 2019

Background and Aims

Liver fibrosis develops in the context of excessive oxidative stress, cell death and accumulation of myofibroblasts (MFs) derived from hepatic stellate cells (HSCs). Ferroptosis is a type of regulated cell death that can be caused by inhibiting the cystine/glutamate antiporter xCT. However, while xCT is induced in various liver diseases, its role in HSC activation and liver fibrosis is unknown. We hypothesized that xCT is required for HSCs to antagonize ferroptosis and remain myofibroblastic.

Methods

xCT activity was disrupted by siRNA or pharmacological inhibitors in MF-HSC cell lines to determine its effect on redox homeostasis, growth, myofibroblastic activity and viability. xCT expression was then determined by RNA sequencing and RT-PCR during primary HSC activation, and its role in HSC trans-differentiation was assessed. For comparison, xCT expression and function were also determined in primary hepatocytes. Finally, the roles of xCT in HSC accumulation and liver fibrosis were assessed in mice treated acutely with CCl4.

Results

Inhibiting xCT in MF-HSCs decreased intracellular glutathione (GSH), suppressed growth and fibrogenesis, and induced cell death. These effects were rescued by antioxidants, an iron chelator, and a canonical ferroptosis inhibitor, but not by inhibitors of apoptosis or necrosis. xCT was dramatically up-regulated during primary HSC activation, and inhibiting xCT suppressed myofibroblastic trans-differentiation and induced ferroptosis. In contrast, healthy hepatocytes were relatively insensitive to ferroptosis induced by xCT inhibition. In vivo, inhibiting xCT systemically reduced MF-HSC accumulation and liver fibrosis after a single dose of CCl4 without exacerbating liver injury or reducing hepatocyte regeneration.

Conclusion

Compared to healthy hepatocytes, MF-HSCs are exquisitely sensitive to ferroptosis induced by inhibiting xCT. In acutely injured livers, systemic inhibitors of xCT can inhibit fibrosis without worsening liver injury. Further research is needed to determine if this therapeutic window remains sufficiently robust to safely target MF-HSCs and inhibit fibrogenesis in chronically injured liver.
Phylogenomics supports a Cenozoic rediversification of the “living fossil” Isoetes
Authors: Wood Daniel , Besnard Guillaume , Beerling David J. , Osborne Colin P. , Christin Pascal-Antoine
Published: December 2019

The fossil record provides an invaluable insight into the temporal origins of extant lineages of organisms. However, establishing the relationships between fossils and extant lineages can be difficult in groups with low rates of morphological change over time. Molecular dating can potentially circumvent this issue by allowing distant fossils to act as calibration points, but rate variation across large evolutionary scales can bias such analyses. In this study, we apply multiple dating methods to genome-wide datasets to infer the origin of extant species of Isoetes, a group of mostly aquatic and semi-aquatic isoetalean lycopsids, which closely resemble fossil forms dating back to the Triassic. Rate variation observed in chloroplast genomes hampers accurate dating, but genome-wide nuclear markers place the origin of extant diversity within this group in the mid-Paleogene, 45-60 million years ago. Our genomic analyses coupled with a careful evaluation of the fossil record indicate that despite resembling forms from the Triassic, extant Isoetes species do not represent the remnants of an ancient and widespread group, but instead have spread around the globe in the relatively recent past.
Leptin signaling and the intervertebral disc: Sex dependent effects of leptin receptor deficiency and Western diet on the spine in a type 2 diabetes mouse model
Authors: Natelson Devorah M. , Lai Alon , Krishnamoorthy Divya , Hoy Rob C. , Iatridis James C. , Illien-Jünger Svenja
Published: December 2019

Type 2 diabetes and obesity are associated with back pain in juveniles and adults and are implicated in intervertebral disc (IVD) degeneration. Hypercaloric Western diets are associated with both obesity and type 2 diabetes. The objective of this study was to determine if obesity and type 2 diabetes result in spinal pathology in a sex-specific manner usingin vivodiabetic and dietary mouse models. Leptin is an appetite-regulating hormone, and its deficiency leads to polyphagia, resulting in obesity and diabetes. Leptin is also associated with IVD degeneration, and increased expression of its receptor was identified in degenerated IVDs. We used young, leptin receptor deficient (Db/Db) mice to mimic the effect of diet and diabetes on adolescents. Db/Db and Control mice were fed either Western or Control diets, and were sacrificed at 3 months of age. Db/Db mice were obese, while only female mice developed diabetes. Female Db/Db mice displayed altered IVD morphology, with increased intradiscal notochordal band area, suggesting delayed IVD cell proliferation and differentiation, rather than IVD degeneration. Motion segments from Db/Db mice exhibited increased failure risk with decreased torsional failure strength. Db/Db mice also had inferior bone quality, which was most prominent in females. We conclude that obesity and diabetes due to impaired leptin signaling contribute to pathological changes in vertebrae, as well as an immature IVD phenotype, particularly of females, suggesting a sex-dependent role of leptin in the spine.
Environmental unpredictability shapes glucocorticoid regulation across populations of tree swallows
Authors: Zimmer Cedric , Taff Conor C. , Ardia Daniel R. , Rose Alexandra P. , Aborn David A. , Johnson L. Scott , Vitousek Maren N.
Published: December 2019

Responding appropriately to challenges is an important contributor to fitness. Variation in the regulation of glucocorticoid hormones, which mediate the phenotypic response to challenges, can therefore influence the ability to persist in a given environment. We compared stress responsiveness in four populations of tree swallows (Tachycineta bicolor) along an environmental gradient to evaluate support for different selective pressures in driving the evolution of glucocorticoid regulation. In accordance with the environmental unpredictability hypothesis, stronger stress responses were seen in more unpredictable environments. Contrary to the reproductive value hypothesis, the stress response was not lower in populations engaging in more valuable reproductive attempts. Populations with stronger stress responses also had stronger negative feedback, which supports a “mitigating” rather than a “magnifying” effect of negative feedback on stress responses. These results suggest that combining a robust stress response with strong negative feedback may be important for persisting in unpredictable or rapidly changing environments.
TandemMapper and TandemQUAST: mapping long reads and assessing/improving assembly quality in extra-long tandem repeats
Authors: Mikheenko Alla , Bzikadze Andrey V. , Gurevich Alexey , Miga Karen H. , Pevzner Pavel A.
Published: December 2019

Extra-long tandem repeats (ETRs) are widespread in eukaryotic genomes and play an important role in fundamental cellular processes, such as chromosome segregation. Although emerging long-read technologies have enabled ETR assemblies, the accuracy of such assemblies is difficult to evaluate since there is no standard tool for their quality assessment. Moreover, since the mapping of long error-prone reads to ETR remains an open problem, it is not clear how to polish draft ETR assemblies. To address these problems, we developed the tandemMapper tool for mapping reads to ETRs and the tandemQUAST tool for polishing ETR assemblies and their quality assessment. We demonstrate that tandemQUAST not only reveals errors in and evaluates ETR assemblies, but also improves them. To illustrate how tandemMapper and tandemQUAST work, we apply them to recently generated assemblies of human centromeres.
TrkB agonists prevent post-ischemic BDNF-TrkB mediated emergence of refractory neonatal seizures in CD-1 pups
Authors: Kipnis P.A. , Sullivan B.J. , Carter B.M. , Kadam S.D.
Published: December 2019

Refractory neonatal seizures do not respond to first-line anti-seizure medications (ASMs) like phenobarbital (PB), a positive allosteric modulator for GABAA receptors, the most widely used ASM to treat neonatal seizures. GABAA receptor-mediated inhibition is dependent upon neuronal chloride regulation. The electroneutral cation-chloride transporter KCC2 mediates neuronal chloride extrusion; an age-dependent increase of KCC2 expression enables the shift of GABAergic signaling from depolarizing to hyperpolarizing. BDNF-TrkB activation following excitotoxic injury recruits downstream targets like PLCγ1, leading to KCC2 hypofunction. This study investigated the efficacy of partial and full TrkB agonists; LM22A-4 (LM), HIOC and Deoxygedunin (DG) respectively, on PB-refractory seizures, post-ischemic TrkB-pathway activation, and KCC2 membrane stability in a P7 CD-1 mouse model of refractory neonatal seizures. Anti-seizure efficacy was determined by quantifying seizure burdens with continuous video-EEG. LM rescued PB-refractory seizures in a sexually dimorphic manner. LM anti-seizure efficacy was associated with a significant reduction in the post-ischemic phosphorylation of TrkB at Y816, a site known to mediate post-ischemic KCC2 hypofunction via PLCγ1 activation. LM additionally rescued ischemia-induced pKCC2-S940 dephosphorylation preserving its membrane stability. HIOC and DG, two novel full TrkB agonists, also rescued PB-refractoriness and post-ischemic TrkB-PLCγ1 pathway activation. Additionally, chemogenetic inactivation of TrkB significantly reduced post-ischemic neonatal seizure burdens at P7. Developmental expression profiles of TrkB and KCC2 in naïve pups identified developmental differences that may underlie the sex-dependent variance in anti-seizure efficacy. These results support a novel role for the TrkB receptor in the emergence of age-dependent refractory neonatal seizures.
Evolutionary rescue and drug resistance on multicopy plasmids
Authors: Santer Mario , Uecker Hildegard
Published: December 2019

Bacteria often carry “extra DNA” in form of plasmids in addition to their chromosome. Many plasmids have a copy number greater than one such that the genes encoded on these plasmids are present in multiple copies per cell. This has evolutionary consequences by increasing the mutational target size, by prompting the (transitory) co-occurrence of mutant and wild-type alleles within the same cell, and by allowing for gene dosage effects. We develop and analyze a mathematical model for bacterial adaptation to harsh environmental change if adaptation is driven by beneficial alleles on multicopy plasmids. Successful adaptation depends on the availability of advantageous alleles and on their establishment probability. The establishment process involves the segregation of mutant and wild-type plasmids to the two daughter cells, allowing for the emergence of mutant-homozygous cells over the course of several generations. To model this process, we use the theory of multi-type branching processes, where a type is defined by the genetic composition of the cell. Both factors – the number of adaptive alleles and their establishment probability – depend on the plasmid copy number, and they often do so antagonistically. We find that in the interplay of various effects, a lower or higher copy number may maximize the probability of evolutionary rescue. The decisive factor is the dominance relationship between mutant and wild-type plasmids and potential gene dosage effects. Results from a simple model of antibiotic degradation indicate that the optimal plasmid copy number may depend on the specific environment encountered by the population.
Medicago truncatula Yellow Stripe1-Like3gene is involved in symbiotic nitrogen fixation
Authors: Castro-Rodríguez Rosario , Abreu Isidro , Reguera María , Novoa-Aponte Lorena , Mijovilovich Ana , Jiménez-Pastor Francisco J. , Abadía Javier , Wen Jiangqi , Mysore Kirankumar S. , Álvarez-Fernández Ana , Küpper Hendrik , Imperial Juan , González-Guerrero Manuel
Published: December 2019

Symbiotic nitrogen fixation carried out in legume root nodules requires transition metals. These nutrients are delivered by the host plant to the endosymbiotic nitrogen-fixing bacteria living with the nodule cells, a process in which vascular transport is essential. As occurs in root-to-shoot transport, members of the Yellow Stripe-Like (YSL) family of metal transporters should also be required for root-to-nodule metal delivery. The genome of the model legumeMedicago truncatulaencodes for eight YSL proteins, four of them with a high degree of similarity toArabidopsis thalianaYSLs involved in long-distance metal trafficking. Among them, MtYSL3 is a plasma membrane protein expressed by vascular cells in roots and nodules, and by cortical nodule cells. Reducing expression levels of this gene had no major effect on plant physiology when assimilable nitrogen was provided in the nutrient solution. However, nodule functioning was severely impaired, with a significant reduction of nitrogen fixation capabilities. Further, iron and zinc accumulation and distribution changed. Iron was retained in the apical region of the nodule, while zinc became strongly accumulated in the nodule veins in theysl3mutant. These data suggest a role of MtYSL3 in vascular delivery of iron and zinc to symbiotic nitrogen fixation.

Highlight

Medicago truncatulaYSL3 transporter is required for optimal nitrogen fixation in root nodules, mediating iron and zinc distribution in these organs.
An RNA degradation complex required for silencing of Polycomb target genes
Authors: Zhou Haining , Shipkovenska Gergana , Kalocsay Marian , Zhang Jiuchun , Luo Zhenhua , Gygi Steven P. , Moazed Danesh
Published: December 2019

Polycomb Repressive Complex (PRC) 1 and 2 are histone-modifying and chromatin-binding complexes that are required for silencing of developmental regulatory genes and genes that control cellular proliferation. Their gene silencing functions are thought to involve chromatin compaction and condensate formation but whether other mechanisms contribute to silencing is unknown. Here we show that the rixosome, a conserved RNA degradation complex with roles in ribosomal RNA processing and heterochromatic RNA degradation in fission yeast, associates with human PRC complexes, is recruited to promoters of Polycomb target genes in differentiated cell lines and embryonic stem cells, and is required for efficient silencing of Polycomb target genes. These findings reveal an unanticipated role for RNA degradation in Polycomb-mediated silencing.
Small fixed‐loop transient electromagnetic in tunnel forward geological prediction
Authors: Su Maoxin , Xia Teng , Xue Yiguo , Mao Deqiang , Qiu Daohong , Zhu Jianye , Zhao Ying , Wang Peng
Published: December 2019

Tunnel forward geological prediction is indispensable to tunnel construction. The transient electromagnetic method is widely used in the field of tunnel forward geological prediction. A small fixed‐loop transient electromagnetic method adapted to the limited space of a tunnel face is proposed for tunnel forward geological prediction for the first time. This method makes use of a large number of non‐central points inside the loop. The obtained numerical simulation and field data show opposite trends owing to mutual inductance and self‐inductance. A correction method for the field value of non‐central points is proposed. The influences of different parameters are verified and the correction function is established by a test method. The validity of the correction function is verified through controlled field tests. The small fixed‐loop transient electromagnetic has been successfully applied to a tunnel under the Weiwu expressway. This method can effectively improve the detection depth and better detect unfavourable geological bodies, such as karsts in front of the tunnel face.
Do reading comprehension assessment tests result in the same reading profile? A study of Spanish primary school children
Authors: Calet Nuria , López‐Reyes Rocío , Jiménez‐Fernández Gracia
Published: December 2019

Background

Detecting reading comprehension difficulties is challenging because many factors are involved in comprehension ability. Various reading comprehension tests can be used to detect difficulties but often do not yield the same results.

Method

Our aim was to analyse the agreement between three commonly used standardised reading comprehension tests (ECOMPLEC, ACL and PROLEC‐R) in the detection of reading comprehension difficulties in Spanish. A total of 139 children (72 fifth graders and 67 sixth graders) at the same public‐sector school participated in this study. The three reading comprehension tests were administered, together with word and nonword reading, vocabulary and nonverbal intelligence measures.

Results

Modest intercorrelations among the tests were found. The consistency of classification for each reading profile across the three reading comprehension tests was low. The results show different reading comprehension profiles depending on the test used.

Conclusions

It is important to use more than one instrument to diagnose reading comprehension difficulties, due to the complexity involved. Furthermore, knowledge of the characteristics of each reading comprehension test is essential to the choice of test. The educational implications of children being wrongly diagnosed are discussed.
Lipoprotein‐associated phospholipase A2 predicts lower limb ischemia in hemodialysis subjects
Authors: De Mauri Andreana , Vidali Matteo , Chiarinotti Doriana , Dianzani Umberto , Rolla Roberta
Published: December 2019

Hemodialyzed patients (HD) have high prevalence of peripheral arterial disease. In the general population, lipoprotein‐associated phospholipase A2 (Lp‐PLA2) is associated with peripheral arterial disease but no data are available for renal subjects. The aim of this study was to evaluate the relationship between Lp‐PLA2 and lower limb ischemia among dialyzed patients. One hundred and two dialyzed subjects, with median (IQR) age of 71 (59‐78) years, enrolled in June 2013 and followed until June 2018, were investigated for Lp‐PLA2 activity and the occurrence of peripheral arterial disease and lower limb ischemia. The median (IQR) levels of Lp‐PLA2 were 184 nmol/min/mL (156.5‐214.5). The 43 HD patients with abnormal Lp‐PLA2 activity (>194 nmol/min/mL) had higher levels of total and LDL‐cholesterol, ApoB/A1 ratio, and higher occurrence of lower limb ischemia during the follow up (44% vs 17%, P = .003). In multivariate analysis, Lp‐PLA2 activity (P = .018) and diabetes (P < .001) were independently associated with time to lower limb ischemia, and when the presence of previous PAD was added to the multivariate model, only presence of previous PAD (P < .001) and Lp‐PLA2 (P = .003) remained associated. Lp‐PLA2 is an independent predictor of lower limb ischemia in dialyzed patients.
How Efficient is the French Less‐Favoured Area Programme?
Authors: Vollet Dominique , Kirsch Alessandra
Published: December 2019

Evaluation of the French Less Favoured Area (LFA) agricultural programme over the period 2007–2013 calls into question the cost‐efficiency of this multi‐objective programme. This article confirms the multiplicity of objectives assigned to this programme, namely to maintain a sustainable agriculture in mountainous areas through income support for farmers in these disadvantaged areas; and thus more indirectly, to enhance the attractiveness of these agricultural areas. The environmental assessment of farms in the FADN network showed that the French LFA programme did help to support the most environmentally friendly dairy and cattle farms in mountainous areas via support for the income levels of these livestock farms. However, the analysis also shows that the LFA criteria are not sufficiently specific to have the required impacts on grassland management practices that would lead to specific defined environmentally friendly practices and improvements. Overall, and in spite of its longstanding and multi‐objective nature, the French LFA programme has been effective both from an economic perspective in that it inspires confidence among economic agents; and also to some extent from a general environmental perspective by providing support for farms which hold most of the permanent grassland, and associated amenities.
Identification and characterization of the peptides with calcium‐binding capacity from tilapia (Oreochromis niloticus) skin gelatin enzymatic hydrolysates
Authors: Bingtong Liu , Yongliang Zhuang , Liping Sun
Published: December 2019

The aim of this study was to isolate and identify the peptides with calcium‐binding capacity from the different tilapia skin gelatin enzymatic hydrolysates. The complex protease was selected and its hydrolysates were further separated using gel filtration chromatography (Sephadex G‐25) and reverse phase high‐performance liquid chromatography. Two purified peptides with strong calcium‐binding capacity were identified as Tyr‐Gly‐Thr‐Gly‐Leu (YGTGL, 509.25 Da) and Leu‐Val‐Phe‐Leu (LVFL, 490.32 Da). The calcium‐binding capacities of YGTGL and LVFL reached 76.03 and 79.50 µg/mg, respectively. The structures of the complex of purified peptides and calcium (YGTGL‐Ca and LVFL‐Ca) were characterized by ultraviolet‐visible spectroscopy (UV‐VIS), scanning electron microscopy (SEM), X‐ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and mass spectrometry (LC‐MS/MS). The results of UV‐VIS, SEM, and XRD indicated that YGTGL‐Ca and LVFL‐Ca were formed as new compounds. The results of FTIR and LC‐MS/MS indicated the nitrogen atom of the amino group and the oxygen atom of the carboxyl group in terminates of the peptides provided primary binding sites. Moreover, the hydrophobic amino acids in purified peptides could provide more chelating spaces. This study was of great significance for the development of calcium supplement foods.

Practical Application

Compared with inorganic calcium and organic calcium, the bioactive gelatin peptide chelated calcium has the characteristics of high utilization rate, high solubility, and high absorption rate. The raw materials are extracted from the tilapia processed waste, which reduce the cost, make full use of resources, and improve the bioavailability. The tilapia skin gelatin peptide calcium chelate can be directly absorbed by the human body, and the absorption efficiency is high, further improving the resource utilization rate and having high economic benefits, which is a comprehensive supplement that can also be used as a functional food.
Chemical compositions and antioxidant activity of adlay seed (Coixlachryma‐jobi L.) oil extracted from four main producing areas in China
Authors: He Chaojun , Li Ziyong , Liu Hongxia , Zhang Haining , Wang Liye , Chen Hong
Published: December 2019

Adlay oil (AO) is an important component of adlay seeds that has many beneficial functions to human health. In this study, the variations in the chemical composition and antioxidant activity of AOs extracted from adlay samples obtained from four main producing areas of China were first investigated. Results revealed that the AO of the adlay samples varied from 7.398 ± 0.486% to 8.464 ± 0.725%. The highest contents of total fatty acid, triolein, total phenolic, and total flavonoid were observed in Xingren AO, whereas coixol content was found to be highest in Pucheng AO. The AO samples were grouped successfully in accordance with the origins by partial least squares–discriminant analysis and hierarchical cluster analysis based on the contents of the chemical components. Furthermore, AOs exhibited considerable levels of 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) radical scavenging activity (IC50, 0.924 ± 0.113 to 1.116 ± 0.109 mg/mL) radical scavenging activity, ferric‐reducing antioxidant power (FRAP) activity (EC50, 0.019 ± 0.002 to 0.028 ± 0.002 mg/mL) activity, and β‐carotene‐linoleic acid bleaching activity (IC50, 0.233 ± 0.008 to 0.414 ± 0.012 mg/mL) activity. Total phenolic and total flavonoid both demonstrated highest correlation with ABTS values (r = −0.952 and r = −0.960, respectively). The results derived from above studies suggest that geographic origin has a certain influence on the phytochemical profiles and antioxidant activity of the AOs.

Practical Application

The chemical composition and antioxidant activity of adlay oils extracted from the adlay samples obtained from four main producing areas of China were evaluated, including total fatty acid, triolein, total phenolic, and total flavonoid, and ABTS radical scavenging activity, FRAP activity, and β‐carotene‐linoleic acid bleaching activity.
The rose and the name: the unresolved debate on biotechnological terms
Authors: Domínguez Martí , Peretó Juli , Porcar Manuel
Published: December 2019

The largest survey on the perception of synthetic biology‐related disciplines (Porcar et al., 2019,EMBO Rep 20) recently revealed that the Spanish society does not have a very positive perception of the term synthetic biology. On the other hand, the terms biotechnology and even genetic engineering received relatively higher scores. The issue of nomenclature and perception is a classical one in science perception studies. Synthetic biologists have been debating their neologism (Synthetic Biology, from now on SB) for years. Even in a 2006 blog, Rob Carlson discussed the various labels for the new field, such as intentional biology, constructive biology, natural engineering, synthetic genomics and biological engineering. This diversity of names, along with the above mentioned negative public perception of the term synthetic biology, raises the question on whether the term itself is suitable or whether it could, in an extreme scenario, be replaced by another combining scientific consensus with public acceptance.
Bioengineered Escherichia coli Nissle 1917 for tumour‐targeting therapy
Authors: Yu Xiaoli , Lin Changsen , Yu Jing , Qi Qingsheng , Wang Qian
Published: December 2019

Bacterial vectors, as microscopic living ‘robotic factories’, can be reprogrammed into microscopic living ‘robotic factories’, using a top‐down bioengineering approach to produce and deliver anticancer agents. Most of the current research has focused on bacterial species such as Salmonella typhimurium or Clostridium novyi. However, Escherichia coli Nissle 1917 (EcN) is another promising candidate with probiotic properties. EcN offers increased applicability for cancer treatment with the development of new molecular biology and complete genome sequencing techniques. In this review, we discuss the genetics and physical properties of EcN. We also summarize and analyse recent studies regarding tumour therapy mediated by EcN. Many challenges remain in the development of more promising strategies for combatting cancer with EcN.
A functional deconstructive approach to mixotrophic phytoplankton responds better to local, regional and biogeographic predictors than species
Authors: Moresco Geovani Arnhold , Bortolini Jascieli Carla , Rodrigues Luzia Cleide , Jati Susicley , Machado Velho Luiz Felipe
Published: December 2019

The use of deconstructive approaches, such as functional classification models, can be an important tool for understanding aquatic systems. This study aimed to evaluate the distribution and community structure of mixotrophic flagellates in lakes of four large Brazilian floodplain systems, those of Amazon River, Araguaia River, Pantanal and upper Paraná River, in contrasting hydrological periods. A partial redundancy analysis (pRDA) was used to estimate the relative roles of environmental, spatial and biogeographic factors on both the entire community and a deconstructive approach using Reynolds' mixotrophic flagellate functional groups (RFGs). High environmental variability was found between the rainy and dry periods, mostly for the Amazon floodplain system. We identified 135 taxa and seven RFGs of mixotrophic flagellates: E, Lo, Q, W1, W2, Ws and Y. A permanova evidenced that biomass of mixotrophic flagellate RFGs reflected differences among floodplains and between hydrological periods. Our results showed that the use of RFGs better summarises the mixotrophic phytoplankton metacommunity structure when compared to the use of the entire community. The pRDA showed that explanatory matrices explained up to 37% of variation in the community. Environmental, spatial and biogeographic factors were important to explain the structure of the mixotrophic flagellates; however, the importance of the different components seemed to depend on the hydrological period and the traits of each RFG.
Periovulatory oviductal fluid decreases sperm protein kinase A activity, tyrosine phosphorylation, and in vitro fertilization in pig
Authors: Zapata‐Carmona Héctor , Soriano‐Úbeda Cristina , París‐Oller Evelyne , Matás Carmen
Published: December 2019

Background

Molecules from the female reproductive tract modulate capacitation and function of sperm cells in vivo. These molecules vary in a quantitative and qualitative manner throughout the estrous cycle.

Objectives

This work evaluates the effect of using various female reproductive fluids on capacitation and fertilization of pig spermatozoa in vitro.

Material and methods

The effects of culturing spermatozoa in different fluids on the levels of sperm protein kinase A (pPKA), tyrosine phosphorylation, acrosome reaction, and in vitro fertilization (IVF) were evaluated. The fluids tested were as follows: oviductal fluid (OF) from five phases of the estrous cycle, namely early and late follicular (OF‐EF, OF‐LF), early and late luteal (OF‐EL, OF‐LL) and periovulatory (pOF), follicular fluid from medium‐sized follicles, and secretions of cumulus‐oocyte complexes (conditioned medium).

Results

The pPKAs and tyrosine phosphorylation were decreased by OF‐EF, OF‐LF, OF‐EL, and pOF but not by follicular fluid and conditioned medium. OF‐EF, OF‐LF, and pOF also decreased the sperm acrosome reaction. Moreover, the effect of pOF on pPKAs and tyrosine phosphorylation was reversible. In in vitro fertilization, OF‐EF, OF‐LF, OF‐EL, and pOF reduced the percentage of penetrated oocytes, the mean number of spermatozoa per penetrated oocyte, and increased monospermy.

Conclusion

OF from follicular, early luteal, and periovulatory phases of the estrous cycle modulates the sperm protein phosphorylation as well as the acrosome reaction involved in capacitation and increases monospermic fertilization in in vitro fertilization. Our findings suggest that fluids from the female reproductive tract could be used as additives in porcine IVF systems to modulate sperm‐oocyte interaction.
Diagnostic value of implantable loop recorder in patients undergoing cryoballoon ablation of atrial fibrillation
Authors: Kusiak Aleksander , Jastrzębski Marek , Bednarski Adam , Kułakowski Piotr , Piotrowski Roman , Koźluk Edward , Baszko Artur , Czarnecka Danuta
Published: December 2019

Background

Due to limited data, implantable loop recorders (ILR) are not currently recommended by the guidelines to routinely monitor patients after atrial fibrillation (AF) ablation.

Aims

To validate the diagnostic value of ILR after AF ablation, modern generation ILRs (LINQ) were implanted in patients scheduled for cryoballoon ablation of AF (CBA).

Methods

We included 29 patients with frequent and symptomatic episodes of paroxysmal AF. ILR was implanted 3 months prior to CBA, and data were collected before and for 6 months after the procedure. The device was programmed to maximize sensitivity of AF/ atrial tachycardia (AT) detection. All EGM recordings were “manually” assessed and annotated as true AF, pseudo AF, unrecognized AF, and episodes with no EGM available. Duration and episode‐based standard performance metrics were evaluated.

Results

A total number of 5,842 episodes were recorded. A total of 4,403 episodes were true AF, 453 episodes were pseudo AF, and 986 episodes had no EGM available. The device did not recognize 144 episodes of AF. Duration‐based sensitivity was 95.2%, duration‐based specificity 99.9%, duration‐based PPV 99.2%, duration‐based NPV 99.9%, episode‐based sensitivity 98.0%, and episode‐based PPV 91.0%. Misdiagnosis happened in 1 in 10 episodes. Total data review time was 166 hr.

Conclusions

Implantable loop recorders is a valuable tool in evaluation of AF episodes in patients undergoing CBA. However, for high precision all recorded episodes need to be evaluated “manually.” The memory storage space is too low for frequent AF episodes, resulting in overwriting of stored EGMs and data loss.
Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct‐acting antiviral drugs
Authors: Naveed Mariam , Ali Amjad , Sheikh Nadeem , Rafique Shazia , Idrees Muhammad
Published: December 2019

Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG‐IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct‐acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG‐IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct‐acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon‐stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV‐infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti‐HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.
Gene expression profiles in bovine granulocytes reflect the aberration of liver functions
Authors: Kizaki Keiichiro , Kageyama Tomomi , Toji Noriyuki , Koshi Katsuo , Sasaki Kouya , Yamagishi Norio , Ishiguro‐Oonuma Toshina , Takahashi Toru , Hashizume Kazuyoshi
Published: December 2019

Liver performs several important functions; however, predicting its functions is difficult. Methods of analyzing gene expression profiles, for example, microarray, provide functional information of tissues. Liver and peripheral blood leukocytes (PBLs) were collected from Holstein cows subjected to two different physiological conditions (non‐pregnant and pregnant), and PBLs were fractionated by gradient cell separation. RNA from PBLs and liver were applied to oligo‐DNA microarray and reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). It revealed a group of stable bovine liver genes under constant physiological conditions. When they applied to physiological conditions including non‐pregnant and pregnant, the profiles of some genes in liver were consistent with those in PBLs. Microarray data subjected to a principal component analysis (PCA) showed that the hepatic gene expression profiles were more consistent with those of granulocytes than mononuclear cells. The relationship of gene profiles in liver with granulocytes was confirmed by RT‐qPCR and hierarchical cluster analysis. Gene profiles of granulocytes were more reliable than those of mononuclear cells, which reflected liver functions. These results suggest that the genes expressed in PBLs, particularly granulocytes, may be convenient bioindicators for the diagnosis of clinical disorder and/or detecting aberration of liver functions in cows subjected to different physiological conditions.
AML through the prism of molecular genetics
Authors: Charrot Sarah , Armes Hannah , Rio‐Machin Ana , Fitzgibbon Jude
Published: December 2019

Modern management of acute myeloid leukaemia (AML) relies on the integration of phenotypic and genetic data to assign classification, establish prognosis, enhance monitoring and guide treatment. The prism through which we can now disperse a patient's leukaemia, interpret and apply our understanding has fundamentally changed since the completion of the first whole‐genome sequencing (WGS) of an AML patient in 2008 and where possible, many clinicians would now prefer to delay treatment decisions until the karyotype and genetic status of a new patient is known. The success of global sequencing initiatives such as The Cancer Genome Atlas (TCGA) have brought us significantly closer to cataloguing the full spectrum of coding mutations involved in human malignancy. Indeed, genetic capability has raced ahead of our capacity to apply much of this knowledge into clinical practice and we are in the peculiar position of having routine access to genetic information on an individual patient's leukaemia that cannot be reliably interpreted or utilised. This is a measure of how rapid the progress has been, and this rate of change is likely to continue into the foreseeable future as research intensifies on the non‐coding genome and the epigenome, as we scrutinise disease at a single cell level, and as initiatives like Beat AML and the Harmony Alliance progress. In this review, we will examine how interrogation of the coding genome is revolutionising our understanding of AML and improving our ability to underscore differences between paediatric and adult onset, sporadic and inherited forms of disease. We will look at how this knowledge is informing improvements in outcome prediction and the development of novel treatments, bringing us a step closer to personalised therapy for myeloid malignancy.
Novel approaches leading towards peptide GPCR de‐orphanisation
Authors: Hauser Alexander S. , Gloriam David E. , Bräuner‐Osborne Hans , Foster Simon R.
Published: December 2019

The discovery of novel ligands for orphan GPCRs has profoundly affected our understanding of human biology, opening new opportunities for research, and ultimately for therapeutic development. Accordingly, much effort has been directed towards the remaining orphan receptors, yet the rate of GPCR de‐orphanisation has slowed in recent years. Here, we briefly review contemporary methodologies of de‐orphanisation and then highlight our recent integrated computational and experimental approach for discovery of novel peptide ligands for orphan GPCRs. We identified putative endogenous peptide ligands and found peptide receptor sequence and structural characteristics present in selected orphan receptors. With comprehensive pharmacological screening using three complementary assays, we discovered novel pairings of 17 peptides with five different orphan GPCRs and revealed potential additional ligands for nine peptide GPCRs. These promising findings lay the foundation for future studies on these peptides and receptors to characterise their roles in human physiology and disease.