scholarly journals Double-digest RAD-sequencing: do wet and dry protocol parameters impact biological results?

2018 ◽  
Author(s):  
Tristan Cumer ◽  
Charles Pouchon ◽  
Frédéric Boyer ◽  
Glenn Yannic ◽  
Delphine Rioux ◽  
...  
Keyword(s):  
Population Genomics ◽  
Butterfly Species ◽  
List Type ◽  
Rad Sequencing ◽  
New Era ◽  
Snp Calling ◽  
Sequencing Technologies ◽  
Common Beech ◽  
Dna Sampling ◽  
The Impact

ABSTRACTNext-generation sequencing technologies have opened a new era of research in genomics. Among these, restriction enzyme-based techniques such as restriction-site associated DNA sequencing (RADseq) or double-digest RAD-sequencing (ddRADseq) are now widely used in many population genomics fields. From DNA sampling to SNP calling, both wet and dry protocols have been discussed in the literature to identify key parameters for an optimal loci reconstruction.The impact of these parameters on downstream analyses and biological results drawn from RADseq or ddRADseq data has however not been fully explored yet. In this study, we tackled this issue by investigating the effects of ddRADseq laboratory (i.e. wet protocol) and bioinformatics (i.e. dry protocol) settings on loci reconstruction and inferred biological signal at two evolutionary scale using two systems: a complex of butterfly species (Coenonympha sp.) and populations of Common beech (Fagus sylvatica).Results suggest an impact of wet protocol parameters (DNA quantity, number of PCR cycles during library preparation) on the number of recovered reads and SNPs, the number of unique alleles and individual heterozygosity. We also found that bioinformatic settings (i.e. clustering and minimum coverage thresholds) impact loci reconstruction (e.g. number of loci, mean coverage) and SNP calling (e.g. number of SNPs, heterozygosity). We however do not detect an impact of parameter settings on three types of analysis performed with ddRADseq data: measure of genetic differentiation, estimation of individual admixture, and demographic inferences. In addition, our work demonstrates the high reproducibility and low rate of genotyping inconsistencies of the ddRADseq protocol.Thus, our study highlights the impact of wet parameters on ddRADseq protocol with strong consequences on experimental success and biological conclusions. Dry parameters affects loci reconstruction and descriptive statistics but not biological conclusion for the two studied systems. Overall, this study illustrates, with others, the relevance of ddRADseq for population and evolutionary genomics at the inter- or intraspecific scales.

Drug Induced Changes in Cell Organelles

1968 ◽  
Vol 26 ◽  
pp. 110-111
Author(s):  
Sarah A. Luse
Keyword(s):  
Clinical Medicine ◽  
Cell Organelles ◽  
Riboflavin Deficiency ◽  
Drug Induced ◽  
New Era ◽  
Health And Disease ◽  
In The Beginning ◽  
Cellular Pathology ◽  
Induced Changes ◽  
The Impact

In the mid-nineteenth century Virchow revolutionized pathology by introduction of the concept of “cellular pathology”. Today, a century later, this term has increasing significance in health and disease. We now are in the beginning of a new era in pathology, one which might well be termed “organelle pathology” or “subcellular pathology”. The impact of lysosomal diseases on clinical medicine exemplifies this role of pathology of organelles in elucidation of disease today.Another aspect of cell organelles of prime importance is their pathologic alteration by drugs, toxins, hormones and malnutrition. The sensitivity of cell organelles to minute alterations in their environment offers an accurate evaluation of the site of action of drugs in the study of both function and toxicity. Examples of mitochondrial lesions include the effect of DDD on the adrenal cortex, riboflavin deficiency on liver cells, elevated blood ammonia on the neuron and some 8-aminoquinolines on myocardium.

Effect of Nanobionics in crop production- A Review

2020 ◽  
Vol 10 ◽  
Author(s):  
Vinayak Fasake ◽  
Nita Patil ◽  
Zoya Javed ◽  
Mansi Mishra ◽  
Gyan Tripathi ◽  
...  
Keyword(s):  
Crop Production ◽  
Seed Quality ◽  
Negative Impact ◽  
Potential Solution ◽  
New Era ◽  
Mineral Toxicity ◽  
The Impact ◽  
Favourable Situation ◽  
Unique Chemical ◽  
Macro Nutrients

: Nanobionics involves the improvement of plant or plant productivity using nanomaterials. Growth of a plant from a seed encompasses various factors which are directly or indirectly dependent upon the imbibition of micro and macro nutrients and vital elements from the soil. Since most of the nutrition is physiologically unavailable to the plants, it leads to mineral deficiencies in plant and mineral toxicity in soil. Either ways, it is not a favourable situation for the microcosom. The new era of nanotechnology offers a potential solution to the availability of the nutrients to the plants due to its unique chemical and physical properties of nanoparticles. Positive and negative impact of these nanoparticles on seed quality and plant growth varies according to the specific properties of nanoparticles. The present review is an attempt to summarize the impact of nanobionics in agriculture.

scholarly journals Editorial: Education in Europe and the COVID-19 Pandemic

2021 ◽  
Vol 20 (4) ◽  
pp. 393-402
Author(s):  
Sotiria Grek ◽  
Paolo Landri
Keyword(s):  
Global Health ◽  
Liberal Education ◽  
Education For All ◽  
Policy Debate ◽  
Special Issue ◽  
Current Crisis ◽  
New Era ◽  
European Education ◽  
The Impact ◽  
Research And Policy

Although the global Covid-19 pandemic is still affecting our lives enormously, we know that a new era of deep reflection about ‘normality’, our planet and our existence on it has also begun. The ‘Education in Europe and the Covid-19 Pandemic’ double Special Issue intends to be part of this reflexive discussion about the post-pandemic European education policy and research space. This is a space shaped continuously by crises and opportunities, by utopias of a shared progressive and liberal education for all, but also the dystopias of nationalism, populism, climate destruction and now a global health emergency. This editorial offers an overview of the current crisis context and of the articles; further, it positions the journal within the post-pandemic research and policy debate about how to understand the impact of the pandemic on the changing forms of education and its enduring inequalities.

scholarly journals Using Satellite Data for CBRN (Chemical, Biological, Radiological, and Nuclear) Threat Detection, Monitoring, and Modelling

2021 ◽  
Author(s):  
Gary Sutlieff ◽  
Lucy Berthoud ◽  
Mark Stinchcombe
Keyword(s):  
Satellite Data ◽  
Meteorological Data ◽  
Atmospheric Composition ◽  
Chemical Detection ◽  
List Type ◽  
Data Types ◽  
Wide Range ◽  
Future Technologies ◽  
The Impact ◽  
Near Future

Abstract CBRN (Chemical, Biological, Radiological, and Nuclear) threats are becoming more prevalent, as more entities gain access to modern weapons and industrial technologies and chemicals. This has produced a need for improvements to modelling, detection, and monitoring of these events. While there are currently no dedicated satellites for CBRN purposes, there are a wide range of possibilities for satellite data to contribute to this field, from atmospheric composition and chemical detection to cloud cover, land mapping, and surface property measurements. This study looks at currently available satellite data, including meteorological data such as wind and cloud profiles, surface properties like temperature and humidity, chemical detection, and sounding. Results of this survey revealed several gaps in the available data, particularly concerning biological and radiological detection. The results also suggest that publicly available satellite data largely does not meet the requirements of spatial resolution, coverage, and latency that CBRN detection requires, outside of providing terrain use and building height data for constructing models. Lastly, the study evaluates upcoming instruments, platforms, and satellite technologies to gauge the impact these developments will have in the near future. Improvements in spatial and temporal resolution as well as latency are already becoming possible, and new instruments will fill in the gaps in detection by imaging a wider range of chemicals and other agents and by collecting new data types. This study shows that with developments coming within the next decade, satellites should begin to provide valuable augmentations to CBRN event detection and monitoring. Article Highlights There is a wide range of existing satellite data in fields that are of interest to CBRN detection and monitoring. The data is mostly of insufficient quality (resolution or latency) for the demanding requirements of CBRN modelling for incident control. Future technologies and platforms will improve resolution and latency, making satellite data more viable in the CBRN management field

scholarly journals Does agricultural intensification cause tipping points in ecosystem services?

2021 ◽  
Author(s):  
Stephen C. L. Watson ◽  
Adrian C. Newton ◽  
Lucy E. Ridding ◽  
Paul M. Evans ◽  
Steven Brand ◽  
...  
Keyword(s):  
Ecosystem Services ◽  
Agricultural Intensification ◽  
Spatial Dynamics ◽  
Policy Option ◽  
List Type ◽  
Tipping Points ◽  
Software Models ◽  
Non Linear ◽  
Study Interval ◽  
The Impact

Abstract Context Agricultural intensification is being widely pursued as a policy option to improve food security and human development. Yet, there is a need to understand the impact of agricultural intensification on the provision of multiple ecosystem services, and to evaluate the possible occurrence of tipping points. Objectives To quantify and assess the long-term spatial dynamics of ecosystem service (ES) provision in a landscape undergoing agricultural intensification at four time points 1930, 1950, 1980 and 2015. Determine if thresholds or tipping points in ES provision may have occurred and if there are any detectable impacts on economic development and employment. Methods We used the InVEST suite of software models together with a time series of historical land cover maps and an Input–Output model to evaluate these dynamics over an 85-year period in the county of Dorset, southern England. Results Results indicated that trends in ES were often non-linear, highlighting the potential for abrupt changes in ES provision to occur in response to slight changes in underlying drivers. Despite the fluctuations in provision of different ES, overall economic activity increased almost linearly during the study interval, in line with the increase in agricultural productivity. Conclusions Such non-linear thresholds in ES will need to be avoided in the future by approaches aiming to deliver sustainable agricultural intensification. A number of positive feedback mechanisms are identified that suggest these thresholds could be considered as tipping points. However, further research into these feedbacks is required to fully determine the occurrence of tipping points in agricultural systems.

128 Development of an M1-polarized, non-viral chimeric antigen receptor macrophage (CAR-M) platform for cancer immunotherapy

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A141-A141
Author(s):  
Yumi Ohtani ◽  
Kayleigh Ross ◽  
Aditya Dandekar ◽  
Rashid Gabbasov ◽  
Michael Klichinsky
Keyword(s):  
Cancer Immunotherapy ◽  
Chimeric Antigen Receptor ◽  
Scale Up ◽  
Antigen Receptor ◽  
Innate Immune ◽  
List Type ◽  
M1 Phenotype ◽  
The Impact ◽  
Anti Tumor Activity ◽  
Immunosuppressive Factors

BackgroundWe have previously developed CAR-M as a novel cell therapy approach for the treatment of solid tumors.1 CAR-M have the potential to overcome key challenges that cell therapies face in the solid tumor setting – tumor infiltration, immunosuppression, lymphocyte exclusion – and can induce epitope spreading to overcome target antigen heterogeneity. While macrophages transduced with the adenoviral vector Ad5f35 (Ad CAR-M) traffic to tumors, provide robust anti-tumor activity, and recruit and activate T cells, we sought to identify a robust non-viral method of macrophage engineering in order to reduce the cost of goods, manufacturing complexity, and potential immunogenicity associated with viral vectors.MethodsAs innate immune cells, macrophages detect exogenous nucleic acids and respond with inflammatory and apoptotic programs. Thus, we sought to identify a means of mRNA delivery that avoids recognition by innate immune sensors. We screened a broad panel of mRNA encoding an anti-HER2 CAR comprising multiplexed 5’Cap and base modifications using an optimized and scalable electroporation approach and evaluated the impact of interferon-β priming on CAR-M phenotype and function.ResultsWe identified the optimal multiplexed mRNA modifications that led to maximal macrophage viability, transfection efficiency, intensity of CAR expression, and duration of expression. Non-viral HER2 CAR-M phagocytosed and killed human HER2+ tumor cells. Unlike Ad CAR-M, mRNA CAR-M were not skewed toward an M1 state by mRNA electroporation. Priming non-viral CAR-M with IFN-β induced a durable M1 phenotype, as shown by stable upregulation of numerous M1 markers and pathways. IFN-β priming significantly enhanced the anti-tumor activity of CAR but not control macrophages. IFN-β primed mRNA CAR-M were resistant to M2 conversion, maintaining an M1 phenotype despite challenge with various immunosuppressive factors, and converted bystander M2 macrophages toward M1. Interestingly, priming mRNA CAR-M with IFN-β significantly enhanced the persistence of CAR expression, overcoming the known issue of rapid mRNA turnover. RNA-seq analysis revealed that IFN-β priming affected pathways involved in increasing translation and decreasing RNA degradation in human macrophages.ConclusionsWe have established a novel, optimized non-viral CAR-M platform based on chemically modified mRNA and IFN-β priming. IFN-β priming induced a durable M1 phenotype, improved CAR expression, improved CAR persistence, led to enhanced anti-tumor function, and rendered resistance to immunosuppressive factors. This novel platform is amenable to scale-up, GMP manufacturing, and represents an advance in the development of CAR-M.ReferenceKlichinsky M, Ruella M, Shestova O, et al. Human chimeric antigen receptor macrophages for cancer immunotherapy. Nat Biotechnol 2020;38(8):947–953.

scholarly journals Research on the impact of ship traffic flow on the restricted channel segment of the middle Yangtze River based on traffic wave theory

2021 ◽  
Vol 3 (8) ◽  
Author(s):  
Ting Liu ◽  
Gabriel Lodewijks
Keyword(s):  
Traffic Flow ◽  
Flow Rate ◽  
Flow Simulation ◽  
Wave Theory ◽  
Flow Density ◽  
List Type ◽  
Ship Traffic ◽  
Traffic Wave ◽  
The Impact ◽  
Channel Segment

Abstract Abstract On the basis of the influence of dry season on ship traffic flow, the gathering and dissipating process of ship traffic flow was researched with Greenshields linear flow—density relationship model, the intrinsic relationship between the ship traffic congestion state and traffic wave in the unclosed restricted channel segment was emphatically explored when the ship traffic flow in a tributary channel inflows, and the influence law of multiple traffic waves on the ship traffic flow characteristics in unclosed restricted segment is revealed. On this basis, the expressions of traffic wave speed and direction, dissipation time of queued ships and the number of ships affected were provided, and combined with Monte Carlo method, the ship traffic flow simulation model in the restricted channel segment was built. The simulation results show that in closed restricted channel segment the dissipation time of ships queued is mainly related to the ship traffic flow rate of segments A and C, and the total number of ships affected to the ship traffic flow rate of segment A. And in unclosed restricted channel segment, the dissipation time and the total number of ships affected are also determined by the meeting time of the traffic waves in addition to the ship traffic flow rate of segments. The research results can provide the theoretical support for further studying the ship traffic flow in unclosed restricted channel segment with multiple tributaries Article Highlights The inflow of tributaries' ship traffic flows has an obvious impact on the traffic conditions in the unenclosed restricted channel segment. The interaction and influence between multiple ship traffic waves and the mechanism of generating new traffic waves are explained. The expression of both dissipation time of queued ships and the total number of ships affected in the closed and unclosed restricted channel segment are given.

scholarly journals Antibiotics at birth and later antibiotic courses: effects on gut microbiota

2021 ◽  
Author(s):  
Sofia Ainonen ◽  
Mysore V Tejesvi ◽  
Md. Rayhan Mahmud ◽  
Niko Paalanne ◽  
Tytti Pokka ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Control Group ◽  
List Type ◽  
Antibiotic Exposure ◽  
Microbiota Composition ◽  
Long Term Effects ◽  
The Impact ◽  
Antibiotic Courses ◽  
Gut Microbiota Composition

Abstract Background Intrapartum antibiotic prophylaxis (IAP) is widely used, but the evidence of the long-term effects on the gut microbiota and subsequent health of children is limited. Here, we compared the impacts of perinatal antibiotic exposure and later courses of antibiotic courses on gut microbiota. Methods This was a prospective, controlled cohort study among 100 vaginally delivered infants with different perinatal antibiotic exposures: control (27), IAP (27), postnatal antibiotics (24), and IAP and postnatal antibiotics (22). At 1 year of age, we performed next-generation sequencing of the bacterial 16S ribosomal RNA gene of fecal samples. Results Exposure to the perinatal antibiotics had a clear impact on the gut microbiota. The abundance of the Bacteroidetes phylum was significantly higher in the control group, whereas the relative abundance of Escherichia coli was significantly lower in the control group. The impact of the perinatal antibiotics on the gut microbiota composition was greater than exposure to later courses of antibiotics (28% of participants). Conclusions Perinatal antibiotic exposure had a marked impact on the gut microbiota at the age of 1 year. The timing of the antibiotic exposure appears to be the critical factor for the changes observed in the gut microbiota. Impact Infants are commonly exposed to IAP and postnatal antibiotics, and later to courses of antibiotics during the first year of life. Perinatal antibiotics have been associated with an altered gut microbiota during the first months of life, whereas the evidence regarding the long-term impact is more limited. Perinatal antibiotic exposure had a marked impact on the infant’s gut microbiota at 1 year of age. Impact of the perinatal antibiotics on the gut microbiota composition was greater than that of the later courses of antibiotics at the age of 1 year.

scholarly journals DNA Methylation and Intra-Clonal Heterogeneity: The Chronic Myeloid Leukemia Model

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3587
Author(s):  
Benjamin Lebecque ◽  
Céline Bourgne ◽  
Véronique Vidal ◽  
Marc G. Berger
Keyword(s):  
Dna Methylation ◽  
Chronic Myeloid Leukemia ◽  
Fusion Protein ◽  
Myeloid Leukemia ◽  
Kinase Inhibitors ◽  
Single Gene ◽  
Clonal Heterogeneity ◽  
Sequencing Technologies ◽  
Genome Wide ◽  
The Impact

Chronic Myeloid Leukemia (CML) is a model to investigate the impact of tumor intra-clonal heterogeneity in personalized medicine. Indeed, tyrosine kinase inhibitors (TKIs) target the BCR-ABL fusion protein, which is considered the major CML driver. TKI use has highlighted the existence of intra-clonal heterogeneity, as indicated by the persistence of a minority subclone for several years despite the presence of the target fusion protein in all cells. Epigenetic modifications could partly explain this heterogeneity. This review summarizes the results of DNA methylation studies in CML. Next-generation sequencing technologies allowed for moving from single-gene to genome-wide analyses showing that methylation abnormalities are much more widespread in CML cells. These data showed that global hypomethylation is associated with hypermethylation of specific sites already at diagnosis in the early phase of CML. The BCR-ABL-independence of some methylation profile alterations and the recent demonstration of the initial intra-clonal DNA methylation heterogeneity suggests that some DNA methylation alterations may be biomarkers of TKI sensitivity/resistance and of disease progression risk. These results also open perspectives for understanding the epigenetic/genetic background of CML predisposition and for developing new therapeutic strategies.

scholarly journals Anomalous Laterally Stressed Kinetically Trapped DNA Surface Conformations

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Valery V. Prokhorov ◽  
Nikolay A. Barinov ◽  
Kirill A. Prusakov ◽  
Evgeniy V. Dubrovin ◽  
Maxim D. Frank-Kamenetskii ◽  
...  
Keyword(s):  
Electrostatic Interaction ◽  
Mechanical Response ◽  
Persistence Length ◽  
Strong Impact ◽  
List Type ◽  
Surface Charges ◽  
Monomolecular Films ◽  
Chain Approximation ◽  
The Impact ◽  
Positively Charged

Highlights DNA kinking is inevitable for the highly anisotropic 1D–1D electrostatic interaction with the one-dimensionally periodically charged surface. The double helical structure of the DNA kinetically trapped on positively charged monomolecular films comprising the lamellar templates is strongly laterally stressed and extremely perturbed at the nanometer scale. The DNA kinetic trapping is not a smooth 3D—> 2D conformational flattening but is a complex nonlinear in-plane mechanical response (bending, tensile and unzipping) driven by the physics beyond the scope of the applicability of the linear worm-like chain approximation. Abstract Up to now, the DNA molecule adsorbed on a surface was believed to always preserve its native structure. This belief implies a negligible contribution of lateral surface forces during and after DNA adsorption although their impact has never been elucidated. High-resolution atomic force microscopy was used to observe that stiff DNA molecules kinetically trapped on monomolecular films comprising one-dimensional periodically charged lamellar templates as a single layer or as a sublayer are oversaturated by sharp discontinuous kinks and can also be locally melted and supercoiled. We argue that kink/anti-kink pairs are induced by an overcritical lateral bending stress (> 30 pNnm) inevitable for the highly anisotropic 1D-1D electrostatic interaction of DNA and underlying rows of positive surface charges. In addition, the unexpected kink-inducing mechanical instability in the shape of the template-directed DNA confined between the positively charged lamellar sides is observed indicating the strong impact of helicity. The previously reported anomalously low values of the persistence length of the surface-adsorbed DNA are explained by the impact of the surface-induced low-scale bending. The sites of the local melting and supercoiling are convincingly introduced as other lateral stress-induced structural DNA anomalies by establishing a link with DNA high-force mechanics. The results open up the study in the completely unexplored area of the principally anomalous kinetically trapped DNA surface conformations in which the DNA local mechanical response to the surface-induced spatially modulated lateral electrostatic stress is essentially nonlinear. The underlying rich and complex in-plane nonlinear physics acts at the nanoscale beyond the scope of applicability of the worm-like chain approximation.

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