scholarly journals Degradation rate uniformity determines success of oscillations in repressive feedback regulatory networks

2018 ◽  
Vol 15 (142) ◽  
pp. 20180157 ◽  
Author(s):  
Karen M. Page ◽  
Ruben Perez-Carrasco
Keyword(s):  
Regulatory Networks ◽  
Oscillatory Behaviour ◽  
Sustained Oscillations ◽  
Degradation Rates ◽  
Number Of Genes ◽  
Computational Exploration ◽  
The Stability ◽  
Regulatory Functions ◽  
Insight Into

Ring oscillators are biochemical circuits consisting of a ring of interactions capable of sustained oscillations. The nonlinear interactions between genes hinder the analytical insight into their function, usually requiring computational exploration. Here, we show that, despite the apparent complexity, the stability of the unique steady state in an incoherent feedback ring depends only on the degradation rates and a single parameter summarizing the feedback of the circuit. Concretely, we show that the range of regulatory parameters that yield oscillatory behaviour is maximized when the degradation rates are equal. Strikingly, this result holds independently of the regulatory functions used or number of genes. We also derive properties of the oscillations as a function of the degradation rates and number of nodes forming the ring. Finally, we explore the role of mRNA dynamics by applying the generic results to the specific case with two naturally different degradation timescales.

Role of sterics in phosphine-ligated gold clusters

2019 ◽  
Vol 21 (4) ◽  
pp. 1689-1699 ◽  
Author(s):  
Katherine A. Parrish ◽  
Mary King ◽  
Marshall R. Ligare ◽  
Grant E. Johnson ◽  
Heriberto Hernández
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Ionization ◽  
Ligand Exchange ◽  
Gold Clusters ◽  
Solution Phase ◽  
Ionization Mass ◽  
Exchange Reactions ◽  
The Stability ◽  
Insight Into

This study examined the solution-phase exchange reactions of triphenylphosphine (PPh3) ligands on Au8L72+ (L = PPh3) gold clusters with three different tolyl ligands using electrospray ionization mass spectrometry to provide insight into how steric differences in the phosphines influence the extent of ligand exchange and the stability of the resulting mixed-phosphine clusters.

scholarly journals Adding levels of complexity enhances robustness and evolvability in a multilevel genotype–phenotype map

2018 ◽  
Vol 15 (138) ◽  
pp. 20170516 ◽  
Author(s):  
Pablo Catalán ◽  
Andreas Wagner ◽  
Susanna Manrubia ◽  
José A. Cuesta
Keyword(s):  
Protein Folding ◽  
Regulatory Networks ◽  
Phenotypic Expression ◽  
Point Mutations ◽  
Skewed Distribution ◽  
Cellular Biology ◽  
Folding Model ◽  
Number Of Genes ◽  
Genotype Space ◽  
The Stability

Robustness and evolvability are the main properties that account for the stability and accessibility of phenotypes. They have been studied in a number of computational genotype–phenotype maps. In this paper, we study a metabolic genotype–phenotype map defined in toyLIFE , a multilevel computational model that represents a simplified cellular biology. toyLIFE includes several levels of phenotypic expression, from proteins to regulatory networks to metabolism. Our results show that toyLIFE shares many similarities with other seemingly unrelated computational genotype–phenotype maps. Thus, toyLIFE shows a high degeneracy in the mapping from genotypes to phenotypes, as well as a highly skewed distribution of phenotypic abundances. The neutral networks associated with abundant phenotypes are highly navigable, and common phenotypes are close to each other in genotype space. All of these properties are remarkable, as toyLIFE is built on a version of the HP protein-folding model that is neither robust nor evolvable: phenotypes cannot be mutually accessed through point mutations. In addition, both robustness and evolvability increase with the number of genes in a genotype. Therefore, our results suggest that adding levels of complexity to the mapping of genotypes to phenotypes and increasing genome size enhances both these properties.

Instability of Si3N4/, SiC/, and MoSi2/ethanol suspensions

2003 ◽  
Vol 18 (1) ◽  
pp. 45-52 ◽  
Author(s):  
Yoko Fukada ◽  
Patrick S. Nicholson
Keyword(s):  
Photoelectron Spectroscopy ◽  
Inductively Coupled Plasma ◽  
Ammonium Hydroxide ◽  
Inductively Coupled ◽  
Transmission Electron ◽  
Tetramethyl Ammonium Hydroxide ◽  
Powder Addition ◽  
The Stability ◽  
Insight Into

Time-dependent suspension behavior is reported for nonoxide ceramic powders (Si3N4, SiC, and MoSi2) in ethanol. The suspension pH (and therefore the stability) changed with time. X-ray photoelectron spectroscopy, inert gas fusion, inductively coupled plasma, and high-resolution transmission electron microscopy were used to track changes of surface chemistry. The adsorption of the base, tetramethyl ammonium hydroxide (TMAH), is examined. The pH drop on powder addition to pure EtOH was used to gain insight into the role of TMAH coverage of the powder surfaces.

scholarly journals Role of dystroglycan in limiting contraction-induced injury to the sarcomeric cytoskeleton of mature skeletal muscle

2016 ◽  
Vol 113 (39) ◽  
pp. 10992-10997 ◽  
Author(s):  
Erik P. Rader ◽  
Rolf Turk ◽  
Tobias Willer ◽  
Daniel Beltrán ◽  
Kei-ichiro Inamori ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscular Dystrophy ◽  
Pathological Feature ◽  
Passive Tension ◽  
Lengthening Contractions ◽  
Mechanistic Insight ◽  
The Stability ◽  
Muscle Biopsies ◽  
Insight Into

Dystroglycan (DG) is a highly expressed extracellular matrix receptor that is linked to the cytoskeleton in skeletal muscle. DG is critical for the function of skeletal muscle, and muscle with primary defects in the expression and/or function of DG throughout development has many pathological features and a severe muscular dystrophy phenotype. In addition, reduction in DG at the sarcolemma is a common feature in muscle biopsies from patients with various types of muscular dystrophy. However, the consequence of disrupting DG in mature muscle is not known. Here, we investigated muscles of transgenic mice several months after genetic knockdown of DG at maturity. In our study, an increase in susceptibility to contraction-induced injury was the first pathological feature observed after the levels of DG at the sarcolemma were reduced. The contraction-induced injury was not accompanied by increased necrosis, excitation–contraction uncoupling, or fragility of the sarcolemma. Rather, disruption of the sarcomeric cytoskeleton was evident as reduced passive tension and decreased titin immunostaining. These results reveal a role for DG in maintaining the stability of the sarcomeric cytoskeleton during contraction and provide mechanistic insight into the cause of the reduction in strength that occurs in muscular dystrophy after lengthening contractions.

scholarly journals A nanobody-based molecular toolkit provides new mechanistic insight into clathrin-coat initiation

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Linton M Traub
Keyword(s):  
Decisive Role ◽  
Subcellular Location ◽  
Combined Approach ◽  
Mechanistic Insight ◽  
Early Endosomes ◽  
The Stability ◽  
And Function ◽  
Insight Into ◽  
Complementarity Determining Region

Besides AP-2 and clathrin triskelia, clathrin coat inception depends on a group of early-arriving proteins including Fcho1/2 and Eps15/R. Using genome-edited cells, we described the role of the unstructured Fcho linker in stable AP-2 membrane deposition. Here, expanding this strategy in combination with a new set of llama nanobodies against EPS15 shows an FCHO1/2–EPS15/R partnership plays a decisive role in coat initiation. A nanobody containing an Asn-Pro-Phe peptide within the complementarity-determining region 3 loop is a function-blocking pseudoligand for tandem EPS15/R EH domains. Yet, in living cells, EH domains gathered at clathrin-coated structures are poorly accessible, indicating residence by endogenous NPF-bearing partners. Forcibly sequestering cytosolic EPS15 in genome-edited cells with nanobodies tethered to early endosomes or mitochondria changes the subcellular location and availability of EPS15. This combined approach has strong effects on clathrin coat structure and function by dictating the stability of AP-2 assemblies at the plasma membrane.

Cu0.8Mg1.2Si2O6 : a copper-bearing silicate with the low-clinopyroxene structure

2016 ◽  
Vol 80 (2) ◽  
pp. 325-335 ◽  
Author(s):  
Lei Ding ◽  
Céline Darie ◽  
Claire V. Colin ◽  
Pierre Bordet
Keyword(s):  
X Ray Diffraction ◽  
Soft Chemistry ◽  
X Ray ◽  
Cu Content ◽  
Distorted Structure ◽  
Mechanisms Of Formation ◽  
Jahn Teller ◽  
The Stability ◽  
Insight Into

AbstractThe Cu0.8Mg1.2Si2O6 pyroxene has been synthesized using a soft chemistry method. Its crystal structure was determined from powder X-ray diffraction data. Cu0.8Mg1.2Si2O6 crystallizes with the lowclinopyroxene monoclinic structure (space group P21/c). The role of the Jahn-Teller-distorted Cu2+ cation on the stability of this strongly distorted structure is investigated. Cu2+ shows a strong preference for the M2 site, attributed to a better adaptation of its JT-distorted coordination polyhedron to this already distorted and more flexible site. Comparison with previously reported compounds indicates that increasing the Cu content enhances the M2 site distortion, eventually leading to symmetry lowering from orthorhombic Pbca to monoclinic P21/c. These observations bring new insight into the mechanisms of formation and chemical composition of pyroxene minerals in the presence of JT cations.

scholarly journals The Role of Hydraulic Hysteresis on the Hydrological Response of Pyroclastic Silty Covers

Water ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 628 ◽  
Author(s):  
Guido Rianna ◽  
Luca Comegna ◽  
Luca Pagano ◽  
Luciano Picarelli ◽  
Alfredo Reder
Keyword(s):  
Slope Failure ◽  
Hysteretic Behavior ◽  
Recent Experience ◽  
Hydrological Response ◽  
Hydraulic Hysteresis ◽  
The Stability ◽  
Hydrological Effects ◽  
Insight Into

A significant part of the recent geotechnical literature concerning pyroclastic soils is focused on the characterization of the hydrological effects of precipitations and their implications for the stability conditions of unsaturated sloping covers. Recent experience shows that suction-induced strength reduction is influenced by various factors including hydraulic hysteresis. A deeper insight into the hysteretic water retention behavior of these materials and its effects upon their response to dry/wetting conditions is a major goal of this paper, which exploits the data provided by the monitoring of a volcanic ash. Based on the parameters retrieved from data calibration, the hydrological response of a virtual slope subject to one-dimensional rainfall infiltration is investigated by numerical analyses and compared with the results obtained through the usually adopted non-hysteretic approaches. The analysis demonstrates that considering the hysteretic behavior may be crucial for a proper evaluation of the conditions leading to slope failure.

scholarly journals Microtubule acetylation but not detyrosination promotes focal adhesion dynamics and cell migration

2018 ◽  
Author(s):  
Bertille Bance ◽  
Shailaja Seetharaman ◽  
Cécile Leduc ◽  
Batiste Boëda ◽  
Sandrine Etienne-Manneville
Keyword(s):  
Cell Migration ◽  
Focal Adhesion ◽  
Focal Adhesions ◽  
Cell Polarization ◽  
Post Translational Modifications ◽  
Tubulin Acetylation ◽  
Focal Adhesion Turnover ◽  
Regulatory Functions ◽  
Insight Into

AbstractMicrotubules play a crucial role in mesenchymal migration by controlling cell polarity and the turnover of cell adhesive structures on the extracellular matrix. The polarized functions of microtubules imply that microtubules are locally regulated. Here, we investigated the regulation and role of two major tubulin post-translational modifications, acetylation and detyrosination, which have been associated with stable microtubules. Using primary astrocytes in a wound healing assay, we show that these tubulin modifications are independently regulated during cell polarization and differently affect cell migration. In contrast to microtubule detyrosination, αTAT1-mediated microtubule acetylation increases in the vicinity of focal adhesions and promotes cell migration. We further demonstrate that αTAT1 increases focal adhesion turnover by promoting Rab6-positive vesicle fusion at focal adhesions. Our results highlight the specificity of microtubule post-translational modifications and bring new insight into the regulatory functions of tubulin acetylation.

scholarly journals Emerging Role of Extracellular Vesicles in Immune Regulation and Cancer Progression

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3563
Author(s):  
Sonam Mittal ◽  
Prachi Gupta ◽  
Pradeep Chaluvally-Raghavan ◽  
Sunila Pradeep
Keyword(s):  
Extracellular Vesicles ◽  
Cancer Progression ◽  
Immune Regulation ◽  
Therapeutic Intervention ◽  
Tumor Stroma ◽  
Membrane Bound ◽  
Regulatory Functions ◽  
Extracellular Environment ◽  
Insight Into

The development of effective therapies for cancer treatment requires a better understanding of the tumor extracellular environment and a dynamic interaction between tumor cells, the cells of the immune system, and the tumor stroma. Increasing evidence suggests that extracellular vesicles play an important role in this interaction. Extracellular vesicles are nanometer-sized membrane-bound vesicles secreted by various types of cells that facilitate intracellular communication by transferring proteins, various lipids, and nucleic acids, especially miRNAs, between cells. Extracellular vesicles play discrete roles in the immune regulatory functions, such as antigen presentation, and activation or suppression of immune cells. Achieving therapeutic intervention through targeting of extracellular vesicles is a crucial area of research now. Thus, a deeper knowledge of exosome biology and the molecular mechanism of immune regulation is likely to provide significant insight into therapeutic intervention utilizing extracellular vesicles to combat this dreadful disease. This review describes the recent updates on immune regulation by extracellular vesicles in cancer progression and possible use in cancer therapy.

Disintegration of the marine based parts of the last Eurasian Ice Sheet

2020 ◽  
Author(s):  
Hans Petter Sejrup ◽  
Berit Oline Hjelstuen ◽  
Mariana Ramos Esteves ◽  
Henry Patton ◽  
Monica Winsborrow ◽  
...  
Keyword(s):  
Ice Sheets ◽  
Ice Sheet ◽  
Controlling Factors ◽  
Continental Margins ◽  
Ice Streams ◽  
Marine Areas ◽  
The Stability ◽  
Glacial Landforms ◽  
Insight Into

<p> The timing, rates and patterns of retreat of western sectors of the last Eurasian Ice Sheet (EurIS) are poorly constrained, hampered by limited observations from the marine domain. A better knowledge of the deglaciation of the NW European marine areas/continental margins is essential for efforts to understand the role of different controlling factors (such as ice streams, atmospheric and oceanic conditions, relative sea level, morphology and substrate) on the stability of the EurIS, and also for ice-sheet stability in general. Based on new and existing mapping of glacial landforms, together with a compilation of existing and recalibrated dates from the NW European shelf, a new reconstruction of the retreating EurIS between 20 and 14 ka BP will be presented. Our reconstruction suggests an initial modest withdrawal from maximum extent to c. 19 ka BP along the entire western marine-terminating margin. From 19ka the two major marine-terminating ice streams, in the Norwegian Channel and Bear Island Trough, begin to retreat/collapse. This destabilisation leads to rapid interior downdraw and the eventual unzipping of the British-Irish and Fennoscandian ice sheets at c. 18.5 ka BP, and the Barents-Kara and Fennoscandian ice sheets between 16 and 15 ka BP. Based on our new reconstruction and modelling results, the importance of factors controlling the nonsynchronous and rapid deglaciation of marine-based sectors and the implications for the stability of the ice sheet, will be discussed. The chronology and patterns of past marine deglaciations provide contextual insight into ice sheet instabilities and the mechanisms behind, underpinning the ongoing retreat of the Greenland and Antarctic ice sheets today.</p><p> </p>

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