scholarly journals The accidental ally: Nucleosomal barriers can accelerate cohesin mediated loop formation in chromatin

2019 ◽  
Author(s):  
Ajoy Maji ◽  
Ranjith Padinhateeri ◽  
Mithun K. Mitra

AbstractAn important question in the context of the 3D organization of chromosomes is the mechanism of formation of large loops between distant base pairs. Recent experiments suggest that the formation of loops might be mediated by Loop Extrusion Factor proteins like cohesin. Experiments on cohesin have shown that cohesins walk diffusively on the DNA, and that nucleosomes act as obstacles to the diffusion, lowering the permeability and hence reducing the effective diffusion constant. An estimation of the times required to form the loops of typical sizes seen in Hi-C experiments using these low effective diffusion constants leads to times that are unphysically large. The puzzle then is the following, how does a cohesin molecule diffusing on the DNA backbone achieve speeds necessary to form the large loops seen in experiments? We propose a simple answer to this puzzle, and show that while at low densities, nucleosomes act as barriers to cohesin diffusion, beyond a certain concentration, they can reduce loop formation times due to a subtle interplay between the nucleosome size and the mean linker length. This effect is further enhanced on considering stochastic binding kinetics of nucleosomes on the DNA backbone, and leads to predictions of lower loop formation times than might be expected from a naive obstacle picture of nucleosomes.

1990 ◽  
Vol 68 (6) ◽  
pp. 2344-2357 ◽  
Author(s):  
M. Meyer ◽  
K. D. Schuster ◽  
H. Schulz ◽  
M. Mohr ◽  
J. Piiper

Pulmonary diffusing capacities (DL) of NO and CO were determined simultaneously from rebreathing equilibration kinetics in anesthetized paralyzed supine dogs (mean body wt 20 kg) after denitrogenation (replacement of N2 by Ar). During rebreathing the dogs were ventilated in closed circuit with a gas mixture containing 0.06% NO, 0.06% 13C18O, and 1% He in Ar for 15 s, with tidal volume of 0.5 liter and frequency of 60/min. The partial pressures of NO, 13C18O, 16O18O, N2, Ar, CO2, and He in the trachea were continuously analyzed by mass spectrometry. Measurements were performed at various O2 levels characterized by the mean end-expired PO2 during rebreathing (PE'O2). In control conditions ('normoxia,” PE'O2 = 67 +/- 8 Torr) the following mean +/- SD values were obtained (in ml.min-1.Torr-1): DLNO = 52.4 +/- 11.0 and DLCO = 15.4 +/- 2.9. In hypoxia (PE'O2 = 24 +/- 7 Torr) DLNO increased by 11 +/- 8% and DLCO by 19 +/- 10%, and in hyperoxia (PE'O2 = 390 +/- 26 Torr) DLNO decreased to 87 +/- 3% and DLCO to 56 +/- 8% with respect to values in normoxia. DLNO/DLCO of 3.24 +/- 0.06 (hypoxia), 3.38 +/- 0.31 (normoxia), and 5.54 +/- 1.04 (hyperoxia) were significantly higher than the NO/CO Krogh diffusion constant ratio (1.92) predicted for simple diffusion through aqueous layers. With increasing O2 uptake elicited by 2,4-dinitrophenol, DLNO and DLCO increased and DLNO/DLCO remained close to unchanged. The results suggest that the combined effects of diffusion and chemical reaction with hemoglobin limit alveolar-capillary transport of CO. If it is assumed that reaction kinetics of NO with hemoglobin (known to be extremely fast) are not rate limiting for NO uptake, the contribution of the slow chemical reaction with hemoglobin to the total CO uptake resistance (= 1/DLCO) was estimated to be 38% in hypoxia, 41% in normoxia, and 64% in hyperoxia. The various factors expected to restrict the validity of this analysis are discussed, in particular the effects of functional inhomogeneity.


1987 ◽  
Vol 52 (3) ◽  
pp. 663-671 ◽  
Author(s):  
Jiří Hanika ◽  
Vladimír Janoušek ◽  
Karel Sporka

Adsorption data for the impregnation of alumina with an aqueous solution of cobalt dichloride and ammonium molybdate were treated in terms of the Langmuir adsorption isotherm and compared with a mathematical model set up to describe the kinetics of simultaneous impregnation of a support by two components. The effective diffusion coefficients of the two components at 25 °C in a cylindrical particle of alumina were obtained. The validity of the model used was verified qualitatively by comparing the numerical results with the experimental time dependent concentration profiles of the active components in a catalyst particle, measured by electron microanalysis technique.


Genetics ◽  
1974 ◽  
Vol 77 (1) ◽  
pp. 95-104
Author(s):  
J E Sulston ◽  
S Brenner

ABSTRACT Chemical analysis and a study of renaturation kinetics show that the nematode, Caenorhabditis elegans, has a haploid DNA content of 8 x IO7 base pairs (20 times the genome of E. coli). Eighty-three percent of the DNA sequences are unique. The mean base composition is 36% GC; a small component, containing the rRNA cistrons, has a base composition of 51% GC. The haploid genome contains about 300 genes for 4s RNA, 110 for 5s RNA, and 55 for (18 + 28)S RNA.


2021 ◽  
Author(s):  
Cyong-Ru Jhan ◽  
Roshan Satange ◽  
Shun-Ching Wang ◽  
Jing-Yi Zeng ◽  
Yih-Chern Horng ◽  
...  

Abstract The use of a small molecule compound to reduce toxic repeat RNA transcripts or their translated aberrant proteins to target repeat-expanded RNA/DNA with a G4C2 motif is a promising strategy to treat C9orf72-linked disorders. In this study, the crystal structures of DNA and RNA–DNA hybrid duplexes with the -GGGCCG- region as a G4C2 repeat motif were solved. Unusual groove widening and sharper bending of the G4C2 DNA duplex A-DNA conformation with B-form characteristics inside was observed. The G4C2 RNA–DNA hybrid duplex adopts a more typical rigid A form structure. Detailed structural analysis revealed that the G4C2 repeat motif of the DNA duplex exhibits a hydration shell and greater flexibility and serves as a ‘hot-spot’ for binding of the anthracene-based nickel complex, NiII(Chro)2 (Chro = Chromomycin A3). In addition to the original GGCC recognition site, NiII(Chro)2 has extended specificity and binds the flanked G:C base pairs of the GGCC core, resulting in minor groove contraction and straightening of the DNA backbone. We have also shown that Chro-metal complexes inhibit neuronal toxicity and suppresses locomotor deficits in a Drosophila model of C9orf72-associated ALS. The approach represents a new direction for drug discovery against ALS and FTD diseases by targeting G4C2 repeat motif DNA.


1989 ◽  
Vol 4 (2) ◽  
pp. 394-398 ◽  
Author(s):  
V. S. Kaushik ◽  
A. K. Datye ◽  
D. L. Kendall ◽  
B. Martinez-Tovar ◽  
D. S. Simons ◽  
...  

Implantation of nitrogen at 150 KeV and a dose of 1 ⊠ 1018/cm2 into (110) silicon results in the formation of an amorphized layer at the mean ion range, and a deeper tail of nitrogen ions. Annealing studies show that the amorphized layer recrystallizes into a continuous polycrystalline Si3N4 layer after annealing for 1 h at 1200 °C. In contrast, the deeper nitrogen fraction forms discrete precipitates (located 1μm below the wafer surface) in less than 1 min at this temperature. The arcal density of these precipitates is 5 ⊠ 107/cm2 compared with a nuclei density of 1.6 ⊠ 105/cm2 in the amorphized layer at comparable annealing times. These data suggest that the nucleation step limits the recrystallization rate of amorphous silicon nitride to form continuous buried nitride layers. The nitrogen located within the damaged crystalline silicon lattice precipitates very rapidly, yielding semicoherent crystallites of β–Si3N4.


2007 ◽  
Vol 263 ◽  
pp. 189-194
Author(s):  
Ivo Stloukal ◽  
Jiří Čermák

Coefficient of 65Zn heterodiffusion in Mg17Al12 intermetallic and in eutectic alloy Mg - 33.4 wt. % Al was measured in the temperature region 598 – 698 K using serial sectioning and residual activity methods. Diffusion coefficient of 65Zn in the intermetallic can be written as DI = 1.7 × 10-2 m2 s-1 exp (-155.0 kJ mol-1 / RT). At temperatures T ≥ 648 K, where the mean diffusion path was greater than the mean interlamellar distance in the eutectic, the effective diffusion coefficient Def = 2.7 × 10-2 m2 s-1 exp (-155.1 kJ mol-1 / RT) was evaluated. At two lower temperatures, the diffusion coefficients 65Zn in interphase boundaries were estimated: Db (623 K) = 1.6 × 10-12 m2 s-1 and Db (598 K) = 4.4 × 10-13 m2 s-1.


1991 ◽  
Vol 130 (3) ◽  
pp. 457-462 ◽  
Author(s):  
S. C. Wilson ◽  
R. T. Gladwell ◽  
F. J. Cunningham

ABSTRACT Diurnal changes of LH secretion in sexually immature hens of 9, 11, 13 and 15 weeks of age consisted of 25–40% increases in the mean concentrations of LH in plasma between 15.00 and 18.00 h, i.e. between 2 h before and 1 h after the onset of darkness. During this time there was a tendency for the mean contents of LHRH-I in the anterior hypothalamus and posterior hypothalamus to increase by 21–74% and 20–56% respectively. In hens of 9 and 15 weeks, diurnal changes in the plasma concentration of LH closely paralleled those of LHRH-I content in the posterior hypothalamus. In contrast, the diurnal rhythm of LH secretion in hens of 11 and 13 weeks was more marked and plasma concentrations of LH continued to rise steeply between 18.00 and 21.00 h, i.e. between 1 and 4 h after the onset of darkness. At 11 weeks, this was associated with a reduction (P<0·01) in the contents of LHRH-I and LHRH-II, particularly in the anterior hypothalamus. In laying hens, a diurnal decline (P<0·01) in the plasma concentration of LH between 1 and 4 h after the onset of darkness was preceded by a fall (P<0·05) in the content of LHRH-I in the posterior hypothalamus and in the total hypothalamic content of LHRH-II (P<0·01). In all groups of hens, irrespective of the times of day at which tissue was taken, significant (P<0·05–<0·001) correlations between the contents of LHRH-I and LHRH-II in the anterior hypothalamus were observed. It is concluded that a diurnal rhythm of release of LHRH-I may drive the diurnal rhythm of LH secretion. Thus, in sexually immature hens of 9 and 15 weeks and laying hens in which diurnal changes in plasma LH were small there were parallel changes in the content of LHRH-I in the posterior hypothalamus. However, where the plasma concentration of LH was increased substantially, as at 11 weeks, there was a decline in the hypothalamic contents of LHRH-I. A simultaneous fall in the hypothalamic content of LHRH-II raises the possibility of a causal relationship between the activities of LHRH-II, LHRH-I and the release of LH. Journal of Endocrinology (1991) 130, 457–462


2012 ◽  
Vol 16 (12) ◽  
pp. 1346-1352 ◽  
Author(s):  
Renata C. dos Reis ◽  
Ivano A. Devilla ◽  
Diego P. R. Ascheri ◽  
Ana C. O. Servulo ◽  
Athina B. M. Souza

The objective of this paper was to model the drying curves of the leaves of basil (Ocimum basilicum L.) in the infrared at temperatures of 50, 60, 70 and 80 ºC and to evaluate the influence of drying temperature on the color of dried leaves. Drying was conducted in infrared dryer with temperature and greenhouse air circulation. Experimental data were fitted to eight mathematical models. The magnitude of the coefficient of determination (R²), the mean relative error (P), the estimated mean error (SE) and chisquare test (χ2) were used to verify the degree of fitness of the models. From the study it was concluded that: a) the behavior of the drying curves of basil leaves was similar to most agricultural products, the drying times in the infrared were less than the drying times in an oven with air circulation, b) the mathematical drying model proposed by Midilli et al. (2002) was the one which best adjusted to the experimental data, c) the diffusion coefficient ranged from 9.10 x 10-12 to 2.92 x 10-11 m² s-1 and d) the color of the samples was highly influenced by drying, becoming darker due to loss of chlorophyll with increasing temperature.


1988 ◽  
Vol 255 (2) ◽  
pp. H375-H385 ◽  
Author(s):  
M. Miniati ◽  
J. C. Parker ◽  
M. Pistolesi ◽  
J. T. Cartledge ◽  
D. J. Martin ◽  
...  

The reabsorption of albumin from the pleural space was measured in eight dogs receiving 0.5 ml intrapleural injection of 131I-labeled albumin and a simultaneous intravenous injection of 125I-labeled albumin. Plasma curves for both tracers were obtained over 24 h. The 125I-albumin curve served as input function of albumin for interstitial spaces, including pleura, whereas the 131I-albumin curve represented the output function from pleural space. The frequency function of albumin transit times from pleural space to plasma was obtained by deconvolution of input-output plasma curves. Plasma recovery of 131I-albumin was complete by 24 h, and the mean transit time from pleura to plasma averaged 7.95 +/- 1.57 (SD) h. Albumin reabsorption occurred mainly via lymphatics as indicated by experiments in 16 additional dogs in which their right lymph ducts or thoracic ducts were ligated before intrapleural injection. A pleural lymph flow of 0.020 +/- 0.003 (SD) ml.kg-1.h-1 was estimated, which is balanced by a comparable filtration of fluid into the pleural space. This suggests that, under physiological conditions, the subpleural lymphatics represent an important control mechanism of pleural liquid pressure.


2001 ◽  
Vol 44 (4) ◽  
pp. 401-404 ◽  
Author(s):  
Fernanda G. A. Ferraz-Grande ◽  
Massanori Takaki

The germination of endangered species Dalbergia nigra was studied and 30.5° C was found as optimum temperature, although the species presented a broad temperature range where germination occurs and light had no effect. The analysis of kinetics of seed germination confirmed the asynchronized germination below and above the optimum temperature. The light insensitive seed and germination also at high temperatures indicated that D. nigra could occur both in understories and gaps where the mean temperature was high.


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