scholarly journals A unifying model for the propagation of prion proteins in yeast brings insight into the [PSI+] prion

2020 ◽  
Author(s):  
Lemarre Paul ◽  
Sindi S. Suzanne ◽  
Pujo-Menjouet Laurent
Keyword(s):  
Mathematical Modeling ◽  
Guanidine Hydrochloride ◽  
Impulsive Differential Equations ◽  
Valuable Insight ◽  
Mathematical Framework ◽  
Yeast Prion ◽  
Modeling Framework ◽  
Yeast Prions ◽  
Multi Scale ◽  
Insight Into

AbstractThe use of yeast systems to study the propagation of prions and amyloids has emerged as a crucial aspect of the global endeavor to understand those mechanisms. Yeast prion systems are intrinsically multi-scale: the molecular chemical processes are indeed coupled to the cellular processes of cell growth and division to influence phenotypical traits, observable at the scale of colonies. We introduce a novel modeling framework to tackle this difficulty using impulsive differential equations. We apply this approach to the [PSI+] yeast prion, which associated with the misconformation and aggregation of Sup35. We build a model that reproduces and unifies previously conflicting experimental observations on [PSI+] and thus sheds light onto characteristics of the intracellular molecular processes driving aggregate replication. In particular our model uncovers a kinetic barrier for aggregate replication at low densities, meaning the change between prion or prion-free phenotype is a bi-stable transition. This result is based on the study of prion curing experiments, as well as the phenomenon of colony sectoring, a phenotype which is often ignored in experimental assays and has never been modeled. Furthermore, our results provide further insight into the effect of guanidine hydrochloride (GdnHCl) on Sup35 aggregates. To qualitatively reproduce the GdnHCl curing experiment, aggregate replication must not be completely inhibited, which suggests the existence of a mechanism different than Hsp104-mediated fragmentation. Those results are promising for further development of the [PSI+] model, but also for extending the use of this novel framework to other yeast prion or amyloid systems.Author summaryIn the study of yeast prions, mathematical modeling is a powerful tool, in particular when it comes to facing the difficulties of multi-scale systems. In this study, we introduce a mathematical framework for investigating this problem in a unifying way. We focus on the yeast prion [PSI+] and present a simple molecular scheme for prion replication and a model of yeast budding. In order to qualitatively reproduce experiments, we need to introduce a non-linear mechanism in the molecular rates. This transforms the intracellular system into a bi-stable switch and allows for curing to occur, which is a crucial phenomenon for the study of yeast prions. To the best of our knowledge, no model in the literature includes such a mechanism, at least not explicitly. We also describe the GdnHCl curing experiment, and the propagon counting procedure. Reproducing this result requires challenging hypotheses that are commonly accepted, and our interpretation gives a new perspective on the concept of propagon. This study may be considered as a good example of how mathematical modeling can bring valuable insight into biological concepts and observations.

A MATHEMATICAL FRAMEWORK EXHIBITING THE EMERGENCE OF DYNAMIC EXPANSION OF TASK REPERTOIRE IN PHEIDOLE DENTATA

2016 ◽  
Vol 24 (02n03) ◽  
pp. 217-235 ◽  
Author(s):  
JASON M. GRAHAM ◽  
IVAN L. SIMPSON-KENT ◽  
MARC A. SEID
Keyword(s):  
Mathematical Modeling ◽  
Age Groups ◽  
Theoretical Work ◽  
Clear Understanding ◽  
Mathematical Framework ◽  
Modeling Framework ◽  
Age Related ◽  
Pheidole Dentata ◽  
Underlying Mechanisms ◽  
Theoretical Results

The division of labor (DOL) and task allocation (TA) among groups of ants living in a colony is thought to be highly efficient, and key to the robust survival of a colony. A great deal of experimental and theoretical work has been done toward gaining a clear understanding of the evolution of, and underlying mechanisms of these phenomena. Much of this research has utilized mathematical modeling. Here we continue this tradition by developing a mathematical model for a particular aspect of TA, known as age-related repertoire expansion, that has been observed in the minor workers of the ant species Pheidole dentata. In fact, we present a relatively broad mathematical modeling framework based on the dynamics of the frequency with which members of specific age groups carry out distinct tasks. We apply our modeling approach to a specific TA scenario, and compare our theoretical results with experimental data. It is observed that the model predicts perceived behavior, and provides a possible explanation for the aforementioned experimental results.

Study of the resistor material of an automotive spark plug by use of the charge-up effect along with elemental mapping in an electron microprobe

1991 ◽  
Vol 49 ◽  
pp. 742-743
Author(s):  
D. R. Liu ◽  
S. S. Shinozaki ◽  
J. S. Park ◽  
B. N. Juterbock
Keyword(s):  
Electron Microprobe ◽  
Present Report ◽  
Coated Sample ◽  
Valuable Insight ◽  
Elemental Mapping ◽  
Spark Plug ◽  
Carbon Coated ◽  
Electron Image ◽  
Electron Imaging ◽  
Insight Into

The electric and thermal properties of the resistor material in an automotive spark plug should be stable during its service lifetime. Containing many elements and many phases, this material has a very complex microstructure. Elemental mapping with an electron microprobe can reveal the distribution of all relevant elements throughout the sample. In this work, it is demonstrated that the charge-up effect, which would distort an electron image and, therefore, is normally to be avoided in an electron imaging work, could be used to advantage to reveal conductive and resistive zones in a sample. Its combination with elemental mapping can provide valuable insight into the underlying conductivity mechanism of the resistor.This work was performed in a CAMECA SX-50 microprobe. The spark plug used in the present report was a commercial product taken from the shelf. It was sectioned to expose the cross section of the resistor. The resistor was known not to contain the precious metal Au as checked on the carbon coated sample. The sample was then stripped of carbon coating and re-coated with Au.

Quantum Mechanical Interpretation of the Ultra-Low Energy Methyl-Rotation Dynamics in Porous Metal-Organic Frameworks Probed by Low-Frequency Vibrational Spectroscopy and ab initio Simulations

2018 ◽  
Author(s):  
Qi Li ◽  
Adam J. Zaczek ◽  
Timothy M. Korter ◽  
J. Axel Zeitler ◽  
Michael T. Ruggiero
Keyword(s):  
Ab Initio ◽  
Metal Organic Frameworks ◽  
Low Frequency ◽  
Rotor Dynamics ◽  
Quantum Mechanical ◽  
Valuable Insight ◽  
Void Space ◽  
Ab Initio Simulations ◽  
Metal Organic ◽  
Insight Into

<div>Understanding the nature of the interatomic interactions present within the pores of metal-organic frameworks</div><div>is critical in order to design and utilize advanced materials</div><div>with desirable applications. In ZIF-8 and its cobalt analogue</div><div>ZIF-67, the imidazolate methyl-groups, which point directly</div><div>into the void space, have been shown to freely rotate - even</div><div>down to cryogenic temperatures. Using a combination of ex-</div><div>perimental terahertz time-domain spectroscopy, low-frequency</div><div>Raman spectroscopy, and state-of-the-art ab initio simulations,</div><div>the methyl-rotor dynamics in ZIF-8 and ZIF-67 are fully charac-</div><div>terized within the context of a quantum-mechanical hindered-</div><div>rotor model. The results lend insight into the fundamental</div><div>origins of the experimentally observed methyl-rotor dynamics,</div><div>and provide valuable insight into the nature of the weak inter-</div><div>actions present within this important class of materials.</div>

A Review of Phytochemical and Pharmacological Studies of Inula Species

2020 ◽  
Vol 16 (5) ◽  
pp. 557-567
Author(s):  
Aparoop Das ◽  
Anshul Shakya ◽  
Surajit Kumar Ghosh ◽  
Udaya P. Singh ◽  
Hans R. Bhat
Keyword(s):  
Bacterial Infections ◽  
Chemical Constituents ◽  
Valuable Insight ◽  
Important Ingredient ◽  
Pharmacological Activities ◽  
Medicinal Uses ◽  
The Family ◽  
Pharmacological Studies ◽  
Perennial Herbs ◽  
Insight Into

Background: Plants of the genus Inula are perennial herbs of the family Asteraceae. This genus includes more than 100 species, widely distributed throughout Europe, Africa and Asia including India. Many of them are indicated in traditional medicine, e.g., in Ayurveda. This review explores chemical constituents, medicinal uses and pharmacological actions of Inula species. Methods: Major databases and research and review articles retrieved through Scopus, Web of Science, and Medline were consulted to obtain information on the pharmacological activities of the genus Inula published from 1994 to 2017. Results: Inula species are used either alone or as an important ingredient of various formulations to cure dysfunctions of the cardiovascular system, respiratory system, urinary system, central nervous system and digestive system, and for the treatment of asthma, diabetes, cancers, skin disorders, hepatic disease, fungal and bacterial infections. A range of phytochemicals including alkaloids, essential and volatile oils, flavonoids, terpenes, and lactones has been isolated from herbs of the genus Inula, which might possibly explain traditional uses of these plants. Conclusion: The present review is focused on chemical constituents, medicinal uses and pharmacological actions of Inula species and provides valuable insight into its medicinal potential.

scholarly journals Compound heterozygous variants in LAMC3 in association with posterior periventricular nodular heterotopia

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Carla De Angelis ◽  
Alicia B. Byrne ◽  
Rebecca Morrow ◽  
Jinghua Feng ◽  
Thuong Ha ◽  
...  
Keyword(s):  
Cortical Development ◽  
Occipital Cortex ◽  
Compound Heterozygous ◽  
Valuable Insight ◽  
Periventricular Nodular Heterotopia ◽  
Case Presentation ◽  
Malformation Of Cortical Development ◽  
Nodular Heterotopia ◽  
Compound Heterozygous Variants ◽  
Insight Into

Abstract Background Periventricular nodular heterotopia (PNH) is a malformation of cortical development characterized by nodules of abnormally migrated neurons. The cause of posteriorly placed PNH is not well characterised and we present a case that provides insights into the cause of posterior PNH. Case presentation We report a fetus with extensive posterior PNH in association with biallelic variants in LAMC3. LAMC3 mutations have previously been shown to cause polymicrogyria and pachygyria in the occipital cortex, but not PNH. The occipital location of PNH in our case and the proposed function of LAMC3 in cortical development suggest that the identified LAMC3 variants may be causal of PNH in this fetus. Conclusion We hypothesise that this finding extends the cortical phenotype associated with LAMC3 and provides valuable insight into genetic cause of posterior PNH.

scholarly journals Detecting Convergence Trends among EU Universities

Economies ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 42
Author(s):  
Maria Adamakou ◽  
Dimitris Kallioras ◽  
George Petrakos
Keyword(s):  
Methodological Approach ◽  
Basic Research ◽  
Valuable Insight ◽  
Traditional Role ◽  
University Ranking ◽  
Convergence Clubs ◽  
Development Processes ◽  
The Impact ◽  
The Empirical Analysis ◽  
Insight Into

Universities are emerging growth determinants. This is so as, in addition to the fulfillment of their traditional role in teaching and (basic) research, universities, as aptly described within the helix framework, are expected to engage in regional development processes. The paper aims to detect trends of convergence among EU universities in terms of performance. To the best of our knowledge, this topic has not hitherto been examined. The empirical analysis of the paper covers the period 2014–2021, utilizes data obtained from URAP (University Ranking by Academic Performance), and employs the methodological approach of convergence clubs. The findings of the paper provide valuable insight into both theory and policy-making. We conclude that despite the unification of EU educational space, trends of divergence among EU universities are still present, and notable divisions still remain. Consequently, this indicates that the impact of EU universities on the formation of spatial disparities across EU space is not neutral.

scholarly journals Exploration of Alternative Splicing Events in Mesenchymal Stem Cells from Human Induced Pluripotent Stem Cells

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 737
Author(s):  
Ji-Eun Jeong ◽  
Binna Seol ◽  
Han-Seop Kim ◽  
Jae-Yun Kim ◽  
Yee-Sook Cho
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Alternative Splicing ◽  
Functional Enrichment ◽  
Actin Binding ◽  
Pcr Analysis ◽  
Valuable Insight ◽  
Sequencing Analysis ◽  
Induced Pluripotent ◽  
Insight Into

Although comparative genome-wide transcriptomic analysis has provided insight into the biology of human induced pluripotent stem cell-derived mesenchymal stem cells (iMSCs), the distinct alternative splicing (AS) signatures of iMSCs remain elusive. Here, we performed Illumina RNA sequencing analysis to characterize AS events in iMSCs compared with tissue-derived MSCs. A total of 4586 differentially expressed genes (|FC| > 2) were identified between iMSCs and umbilical cord blood-derived MSCs (UCB-MSCs), including 2169 upregulated and 2417 downregulated genes. Of these, 164 differentially spliced events (BF > 20) in 112 genes were identified between iMSCs and UCB-MSCs. The predominant type of AS found in iMSCs was skipped exons (43.3%), followed by retained introns (19.5%), alternative 3′ (15.2%) and 5′ (12.8%) splice sites, and mutually exclusive exons (9.1%). Functional enrichment analysis showed that the differentially spliced genes (|FC| > 2 and BF > 20) were mainly enriched in functions associated with focal adhesion, extracellular exosomes, extracellular matrix organization, cell adhesion, and actin binding. Splice isoforms of selected genes including TRPT1, CNN2, and AP1G2, identified in sashimi plots, were further validated by RT-PCR analysis. This study provides valuable insight into the biology of iMSCs and the translation of mechanistic understanding of iMSCs into therapeutic applications.

scholarly journals Complex community responses underpin biodiversity change following invasion

2021 ◽  
Author(s):  
Alessandra R. Kortz ◽  
Anne E. Magurran
Keyword(s):  
Invasive Species ◽  
Species Richness ◽  
Spatial Scales ◽  
Species Abundance ◽  
Ecological Systems ◽  
Multi Scale ◽  
Mechanistic Approach ◽  
Α Diversity ◽  
Biodiversity Change ◽  
Insight Into

AbstractHow do invasive species change native biodiversity? One reason why this long-standing question remains challenging to answer could be because the main focus of the invasion literature has been on shifts in species richness (a measure of α-diversity). As the underlying components of community structure—intraspecific aggregation, interspecific density and the species abundance distribution (SAD)—are potentially impacted in different ways during invasion, trends in species richness provide only limited insight into the mechanisms leading to biodiversity change. In addition, these impacts can be manifested in distinct ways at different spatial scales. Here we take advantage of the new Measurement of Biodiversity (MoB) framework to reanalyse data collected in an invasion front in the Brazilian Cerrado biodiversity hotspot. We show that, by using the MoB multi-scale approach, we are able to link reductions in species richness in invaded sites to restructuring in the SAD. This restructuring takes the form of lower evenness in sites invaded by pines relative to sites without pines. Shifts in aggregation also occur. There is a clear signature of spatial scale in biodiversity change linked to the presence of an invasive species. These results demonstrate how the MoB approach can play an important role in helping invasion ecologists, field biologists and conservation managers move towards a more mechanistic approach to detecting and interpreting changes in ecological systems following invasion.

A novel synergistic multi-scale modeling framework to predict micro- and meso-scale damage behaviors of 2D triaxially braided composite

2021 ◽  
pp. 105678952110339
Author(s):  
Hongyong Jiang ◽  
Yiru Ren ◽  
Qiduo Jin
Keyword(s):  
Compressive Load ◽  
Scale Model ◽  
Modeling Framework ◽  
Braided Composite ◽  
Multi Scale ◽  
Scale Modeling ◽  
Bridge Model ◽  
Multi Scale Modeling ◽  
Transverse Damage ◽  
Meso Scale

A novel synergistic multi-scale modeling framework with a coupling of micro- and meso-scale is proposed to predict damage behaviors of 2D-triaxially braided composite (2DTBC). Based on the Bridge model, the internal stress and micro damage of constituent materials are respectively coupled with the stress and damage of tow. The initial effective elastic properties of tow (IEEP) used as the predefined data are estimated by micro-mechanics models. Due to in-situ effects, stress concentration factor (SCF) is considered in the micro matrix, exhibiting progressive damage accumulation. Comparisons of IEEP and strengths between the Bridge and Chamis’ theory are conducted to validate the values of IEEP and SCF. Based on the representative volume element (RVE), the macro properties and damage modes of 2DTBC are predicted to be consistent with available experiments and meso-scale simulation. Both axial and transverse damage mechanisms of 2DTBC under tensile or compressive load are revealed. Micro fiber and matrix damage accumulations have significant effects on the meso-scale axial and transverse damage of tows due to multi-scale coupling effects. Different from existing meso-/multi-scale models, the proposed multi-scale model can capture a crucial phenomenon that the transverse damage of tow is vulnerable to micro fiber fracture. The proposed multi-scale framework provides a robust tool for future systematic studies on constituent materials level to larger-scale aeronautical materials.

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