scholarly journals Transcript-specific determinants of pre-mRNA splicing revealed through in vivo kinetic analyses of the 1st and 2nd chemical steps

2020 ◽  
Author(s):  
Michael A. Gildea ◽  
Zachary W. Dwyer ◽  
Jeffrey A. Pleiss
Keyword(s):  
Genetic Variant ◽  
Important Determinant ◽  
Mrna Splicing ◽  
Splicing Regulation ◽  
Order Kinetic ◽  
Ribosomal Protein Genes ◽  
First Order ◽  
Rna Labeling ◽  
Evolutionarily Conserved

SummaryUnderstanding how the spliceosome processes its composite of substrates through the two chemical steps required for mRNA production will be essential to deciphering splicing regulation and mis-regulation. Here we measure the in vivo rates of these steps across the genome by coupling metabolic RNA labeling, targeted sequencing, and first order kinetic modeling. We reveal a wide variety of rates by which introns are removed, that splice site sequences are primary determinants of 1st step rates, and that the 2nd step is generally faster than the 1st step. We show that ribosomal protein genes (RPGs) are spliced faster than non-RPGs at each step, and that RPGs share evolutionarily conserved cis-features which facilitate their splicing. A genetic variant defective at the 1st step shows the expected defect in the 1st step, but an unexpected change in the 2nd step which suggests how co-transcriptional splicing functions as an important determinant of splicing rates.

scholarly journals PLRG1 Is an Essential Regulator of Cell Proliferation and Apoptosis during Vertebrate Development and Tissue Homeostasis

2009 ◽  
Vol 29 (11) ◽  
pp. 3173-3185 ◽  
Author(s):  
André Kleinridders ◽  
Hans-Martin Pogoda ◽  
Sigrid Irlenbusch ◽  
Neil Smyth ◽  
Csaba Koncz ◽  
...  
Keyword(s):  
Cell Cycle Progression ◽  
Tissue Homeostasis ◽  
Mrna Splicing ◽  
Vertebrate Development ◽  
Adult Tissue ◽  
Serum Stimulation ◽  
Evolutionarily Conserved ◽  
Proliferation And Apoptosis ◽  
Dependent Cell

ABSTRACT PLRG1, an evolutionarily conserved component of the spliceosome, forms a complex with Pso4/SNEV/Prp19 and the cell division and cycle 5 homolog (CDC5L) that is involved in both pre-mRNA splicing and DNA repair. Here, we show that the inactivation of PLRG1 in mice results in embryonic lethality at 1.5 days postfertilization. Studies of heart- and neuron-specific PLRG1 knockout mice further reveal an essential role of PLRG1 in adult tissue homeostasis and the suppression of apoptosis. PLRG1-deficient mouse embryonic fibroblasts (MEFs) fail to progress through S phase upon serum stimulation and exhibit increased rates of apoptosis. PLRG1 deficiency causes enhanced p53 phosphorylation and stabilization in the presence of increased γ-H2AX immunoreactivity as an indicator of an activated DNA damage response. p53 downregulation rescues lethality in both PLRG1-deficient MEFs and zebrafish in vivo, showing that apoptosis resulting from PLRG1 deficiency is p53 dependent. Moreover, the deletion of PLRG1 results in the relocation of its interaction partner CDC5L from the nucleus to the cytoplasm without general alterations in pre-mRNA splicing. Taken together, the results of this study identify PLRG1 as a critical nuclear regulator of p53-dependent cell cycle progression and apoptosis during both embryonic development and adult tissue homeostasis.

scholarly journals Splicing factor SRSF1 expands the regulatory logic of microRNA expression

2020 ◽  
Author(s):  
Marija Dargyte ◽  
Julia Philipp ◽  
Christina D. Palka ◽  
Michael D. Stone ◽  
Jeremy R. Sanford
Keyword(s):  
Binding Sites ◽  
Regulatory Elements ◽  
Mrna Splicing ◽  
Splicing Factor ◽  
Stem Loop ◽  
Microrna Biogenesis ◽  
Evolutionarily Conserved ◽  
Rna Interaction

AbstractThe serine and arginine-rich splicing factor SRSF1 is an evolutionarily conserved, essential pre-mRNA splicing factor. Through a global protein-RNA interaction survey we discovered SRSF1 binding sites 25-50nt upstream from hundreds of pre-miRNAs. Using primary miRNA-10b as a model we demonstrate that SRSF1 directly regulates microRNA biogenesis both in vitro and in vivo. Selective 2’ hydroxyl acylation analyzed by primer extension (SHAPE) defined a structured RNA element located upstream of the precursor miRNA-10b stem loop. Our data support a model where SRSF1 promotes initial steps of microRNA biogenesis by relieving the repressive effects of cis-regulatory elements within the leader sequence.

The in vivo regeneration of goldfish rhodopsin and porphyropsin

1986 ◽  
Vol 122 (1) ◽  
pp. 269-275
Author(s):  
A. T. Tsin ◽  
J. M. Flores
Keyword(s):  
Body Weight ◽  
Rate Constant ◽  
Half Life ◽  
Visual Pigment ◽  
Initial Period ◽  
Direct Result ◽  
Order Kinetic ◽  
Kinetic Rate Constant ◽  
First Order

Goldfish with retinas rich in either rhodopsin or porphyropsin were illuminated with bright light and then placed in the dark room to allow visual pigment regeneration. The kinetics of this in vivo pigment regeneration were followed by sampling these animals at regular time intervals. The first-order kinetic rate constant for the initial period of porphyropsin regeneration at 20 degrees C was 8.3 X 10(−3) nmol kg-1 body weight min-1 and the half-life of this reaction was 83 min. At 30 degrees C, the rate constant was increased to 1.4 X 10(−2) nmol kg-1 body weight min-1, yielding a reduced half-life of 49 min. This suggests that the Q10 of porphyropsin regeneration is about 1.7. In goldfish retinas enriched with rhodopsin (62% rhodopsin and 38% porphyropsin), the initial phase of visual pigment regeneration (at 30 degrees C) proceeded at a slower rate (first-order rate constant: 6.5 X 10(−3) nmol kg-1 body weight min-1; half-life of reaction = 106 min) than the rate of porphyropsin regeneration. This suggests that the high proportion of rhodopsin in the retina of goldfish held at 30 degrees C is not a direct result of a faster rate of regeneration of rhodopsin than of porphyropsin.

Leaching Kinetics of Atrazine and Inorganic Chemicals in Tilled and Orchard Soils

2014 ◽  
Vol 28 (2) ◽  
pp. 231-237 ◽  
Author(s):  
Lech W. Szajdak ◽  
Jerzy Lipiec ◽  
Anna Siczek ◽  
Artur Nosalewicz ◽  
Urszula Majewska
Keyword(s):  
Reaction Rate ◽  
Inorganic Compounds ◽  
Model Performance ◽  
Order Reaction ◽  
First Order Reaction ◽  
Order Kinetic ◽  
Time Data ◽  
First Order ◽  
Concentration Changes ◽  
Reaction Constants

Abstract The aim of this study was to verify first-order kinetic reaction rate model performance in predicting of leaching of atrazine and inorganic compounds (K+1, Fe+3, Mg+2, Mn+2, NH4 +, NO3 - and PO4 -3) from tilled and orchard silty loam soils. This model provided an excellent fit to the experimental concentration changes of the compounds vs. time data during leaching. Calculated values of the first-order reaction rate constants for the changes of all chemicals were from 3.8 to 19.0 times higher in orchard than in tilled soil. Higher first-order reaction constants for orchard than tilled soil correspond with both higher total porosity and contribution of biological pores in the former. The first order reaction constants for the leaching of chemical compounds enables prediction of the actual compound concentration and the interactions between compound and soil as affected by management system. The study demonstrates the effectiveness of simultaneous chemical and physical analyses as a tool for the understanding of leaching in variously managed soils.

scholarly journals Enhancing methane production from the invasive macroalga Rugulopteryx okamurae through anaerobic co-digestion with olive mill solid waste: process performance and kinetic analysis

2021 ◽  
Author(s):  
D. de la Lama-Calvente ◽  
M. J. Fernández-Rodríguez ◽  
J. Llanos ◽  
J. M. Mancilla-Leytón ◽  
R. Borja
Keyword(s):  
Anaerobic Digestion ◽  
Solid Waste ◽  
Methane Production ◽  
Methane Yield ◽  
Specific Rate ◽  
Order Kinetic ◽  
Two Phase ◽  
First Order ◽  
Olive Mill Solid Waste ◽  
Olive Mill

AbstractThe biomass valorisation of the invasive brown alga Rugulopteryx okamurae (Dictyotales, Phaeophyceae) is key to curbing the expansion of this invasive macroalga which is generating tonnes of biomass on southern Spain beaches. As a feasible alternative for the biomass management, anaerobic co-digestion is proposed in this study. Although the anaerobic digestion of macroalgae barely produced 177 mL of CH4 g−1 VS, the co-digestion with a C-rich substrate, such as the olive mill solid waste (OMSW, the main waste derived from the two-phase olive oil manufacturing process), improved the anaerobic digestion process. The mixture improved not only the methane yield, but also its biodegradability. The highest biodegradability was found in the mixture 1 R. okamurae—1 OMSW, which improved the biodegradability of the macroalgae by 12.9% and 38.1% for the OMSW. The highest methane yield was observed for the mixture 1 R. okamurae—3 OMSW, improving the methane production of macroalgae alone by 157% and the OMSW methane production by 8.6%. Two mathematical models were used to fit the experimental data of methane production time with the aim of assessing the processes and obtaining the kinetic constants of the anaerobic co-digestion of different combination of R. okamurae and OMSW and both substrates independently. First-order kinetic and the transference function models allowed for appropriately fitting the experimental results of methane production with digestion time. The specific rate constant, k (first-order model) for the mixture 1 R. okamurae- 1.5 OMSW, was 5.1 and 1.3 times higher than that obtained for the mono-digestion of single OMSW and the macroalga, respectively. In the same way, the transference function model revealed that the maximum methane production rate (Rmax) was also found for the mixture 1 R. okamurae—1.5 OMSW (30.4 mL CH4 g−1 VS day−1), which was 1.6 and 2.2 times higher than the corresponding to the mono-digestions of the single OMSW and sole R. okamurae (18.9 and 13.6 mL CH4 g−1 VS day−1), respectively.

MODELLING NITROGEN PROCESSES IN SOIL: MATHEMATICAL DEVELOPMENT AND RELATIONSHIPS

1976 ◽  
Vol 56 (2) ◽  
pp. 71-78 ◽  
Author(s):  
D. R. CAMERON ◽  
C. G. KOWALENKO
Keyword(s):  
Time Dependent ◽  
Rate Coefficients ◽  
Nitrification Rate ◽  
Order Kinetic ◽  
Nitrogen Flow ◽  
First Order ◽  
Interaction Term ◽  
Flow Pathways ◽  
Adsorption Desorption ◽  
Temperature Water

A small subsystem model was developed to simulate the major nitrogen flow pathways in an unsaturated soil treated with ammonium sulphate. A nonlinear Freundlich equilibrium model and a Langmuir kinetic model were used to describe mathematically the adsorption–desorption of soluble NH4+ to the exchangeable and clay-fixed phases, respectively. Time dependent, microbial mediated first-order kinetic models were used to quantify the ammonification and nitrification processes. The subsystem model was then used as a research tool to derive ammonification and nitrification rate coefficients for a preceding incubation experiment conducted using different soil moisture contents and temperatures. The model yields reasonably good fits to the observed data. A subsequent regression analysis relating the coefficients to temperature and moisture pointed out the importance of the temperature–water content interaction term in quantifying microbial mediated processes.

scholarly journals Comparative Study of Chemical Stability of Two H1Antihistaminic Drugs, Terfenadine and ItsIn VivoMetabolite Fexofenadine, Using LC-UV Methods

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Anna Gumieniczek ◽  
Anna Berecka-Rycerz ◽  
Rafał Pietraś ◽  
Izabela Kozak ◽  
Karolina Lejwoda ◽  
...  
Keyword(s):  
Comparative Study ◽  
Chemical Stability ◽  
First Order ◽  
First Order Kinetics ◽  
Kinetics Of Degradation ◽  
Effects Of Temperature ◽  
High Doses ◽  
Antihistaminic Drugs ◽  
Kinetics Of

A comparative study of chemical stability of terfenadine (TER) and itsin vivometabolite fexofenadine (FEX) was performed. Both TER and FEX were subjected to high temperature at different pH and UV/VIS light at different pH and then quantitatively analyzed using new validated LC-UV methods. These methods were used to monitor the degradation processes and to determine the kinetics of degradation for both the compounds. As far as the effects of temperature and pH were concerned, FEX occurred more sensitive to degradation than TER. As far as the effects of UV/VIS light and pH were concerned, the both drugs were similarly sensitive to high doses of light. Using all stress conditions, the processes of degradation of TER and FEX followed the first-order kinetics. The results obtained for these two antihistaminic drugs could be helpful in developing their new derivatives with higher activity and stability at the same time.

Interspike interval dependency from arterial chemoreceptors

1985 ◽  
Vol 59 (5) ◽  
pp. 1566-1570 ◽  
Author(s):  
D. F. Donnelly ◽  
W. F. Nolan ◽  
E. J. Smith ◽  
R. E. Dutton
Keyword(s):  
Carotid Body ◽  
Interspike Interval ◽  
Correlation Coefficients ◽  
Feedback System ◽  
Serial Dependence ◽  
Control Series ◽  
First Order ◽  
System Operating ◽  
Poisson Type

The carotid body impulse generator has been previously characterized as a Poisson-type random process. We examined the validity of this characterization by analyzing sinus nerve spike trains for interspike interval dependency. Fifteen single chemoreceptive afferents were recorded in vivo under hypoxic-hypercapnic conditions, and approximately 1,000 consecutive interspike intervals for each fiber were timed and analyzed for serial dependence. The same set of intervals placed in shuffled order served as a control series without serial dependence. The original spike interval trains showed significantly negative first-order serial correlation coefficients and less variability in joint interval distributions than did the shuffled interval trains. These results suggest that the chemoreceptor afferent train is not random and may reflect a negative feedback system operating within the carotid body that limits variation about a mean frequency.

scholarly journals New Mathematical Modeling Approach for Predicting Microbial Inactivation by High Hydrostatic Pressure

2007 ◽  
Vol 73 (8) ◽  
pp. 2468-2478 ◽  
Author(s):  
Bernadette Klotz ◽  
D. Leo Pyle ◽  
Bernard M. Mackey
Keyword(s):  
Microbial Inactivation ◽  
Inactivation Kinetics ◽  
Published Data ◽  
Model Parameters ◽  
Order Kinetic ◽  
Square Root ◽  
Additional Time ◽  
Decimal Reduction Time ◽  
First Order ◽  
Primary Model

ABSTRACT A new primary model based on a thermodynamically consistent first-order kinetic approach was constructed to describe non-log-linear inactivation kinetics of pressure-treated bacteria. The model assumes a first-order process in which the specific inactivation rate changes inversely with the square root of time. The model gave reasonable fits to experimental data over six to seven orders of magnitude. It was also tested on 138 published data sets and provided good fits in about 70% of cases in which the shape of the curve followed the typical convex upward form. In the remainder of published examples, curves contained additional shoulder regions or extended tail regions. Curves with shoulders could be accommodated by including an additional time delay parameter and curves with tails shoulders could be accommodated by omitting points in the tail beyond the point at which survival levels remained more or less constant. The model parameters varied regularly with pressure, which may reflect a genuine mechanistic basis for the model. This property also allowed the calculation of (a) parameters analogous to the decimal reduction time D and z, the temperature increase needed to change the D value by a factor of 10, in thermal processing, and hence the processing conditions needed to attain a desired level of inactivation; and (b) the apparent thermodynamic volumes of activation associated with the lethal events. The hypothesis that inactivation rates changed as a function of the square root of time would be consistent with a diffusion-limited process.

Neurofilament phosphorylation

1995 ◽  
Vol 73 (9-10) ◽  
pp. 575-592 ◽  
Author(s):  
Harish C. Pant ◽  
Veeranna
Keyword(s):  
Molecular Weight ◽  
Nervous System ◽  
Nervous Tissue ◽  
Important Determinant ◽  
Neurofilament Proteins ◽  
Neurofilament Phosphorylation ◽  
Axonal Compartment

Neurofilament proteins (NFPs) are highly phosphorylated molecules in the axonal compartment of the adult nervous system. The phosphorylation of NFP is considered an important determinant of filament caliber, plasticity, and stability. This process reflects the function of NFs during the lifetime of a neuron from differentiation in the embryo through long-term activity in the adult until aging and environmental insult leads to pathology and ultimately death. NF function is modulated by phosphorylation–dephosphorylation in each of these diverse neuronal states. In this review, we have summarized some of these properties of NFP in adult nervous tissue, mostly from work in our own laboratory. Identification of sites phosphorylated in vivo in high molecular weight NFP (NF-H) and properties of NF-associated and neural-specific kinases phosphorylating specific sites in NFP are described. A model to explain the role of NF phosphorylation in determining filament caliber, plasticity, and stability is proposed.Key words: neurofilament proteins, phosphorylation, kinases, phosphatases, regulators, inhibitors, multimesic complex, domains.

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