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1.
J Food Sci ; 87(11): 4796-4807, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36181485

RESUMO

Isochoric impregnation was explored as a novel pressure-assisted infusion technique to fortify plant materials with bioactive compounds. Apple and potato cylinders were impregnated with a sucrose solution containing 4% ascorbic acid (AA) while freezing under isochoric conditions. Isochoric impregnation resulted in greater infusion of AA compared to infusion at atmospheric pressure, which demonstrated the feasibility of this impregnation technology. Processing temperatures (-3°C and -5°C) and processing times (1, 3, and 5 h) significantly affected the AA infusion. The AA content values ranged from 446 to 516 mg/100 g for apples and 322 to 831 mg/100 g for sweet potatoes under isochoric conditions. For both plant materials, isochoric impregnation at -3°C did not cause major changes in texture and microstructure of the biological tissues. These results indicated that isochoric impregnation of solid foods could be a feasible technology for infusion of bioactive compounds without significantly altering their matrix. PRACTICAL APPLICATION: The findings of this study showed that the use of isochoric impregnation as a fortification technique is a promising way to develop fresh-like and value-added products with improved nutrition during preservation at subfreezing temperatures.


Assuntos
Malus , Solanum tuberosum , Isocoros , Congelamento , Ácido Ascórbico
2.
Genome Biol Evol ; 14(8)2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35867377

RESUMO

Protein coding genes terminate with one of three stop codons (TAA, TGA, or TAG) that, like synonymous codons, are not employed equally. With TGA and TAG having identical nucleotide content, analysis of their differential usage provides an unusual window into the forces operating on what are ostensibly functionally identical residues. Across genomes and between isochores within the human genome, TGA usage increases with G + C content but, with a common G + C → A + T mutation bias, this cannot be explained by mutation bias-drift equilibrium. Increased usage of TGA in G + C-rich genomes or genomic regions is also unlikely to reflect selection for the optimal stop codon, as TAA appears to be universally optimal, probably because it has the lowest read-through rate. Despite TAA being favored by selection and mutation bias, as with codon usage bias G + C pressure is the prime determinant of between-species TGA usage trends. In species with strong G + C-biased gene conversion (gBGC), such as mammals and birds, the high usage and conservation of TGA is best explained by an A + T → G + C repair bias. How to explain TGA enrichment in other G + C-rich genomes is less clear. Enigmatically, across bacterial and archaeal species and between human isochores TAG usage is mostly unresponsive to G + C pressure. This unresponsiveness we dub the TAG paradox as currently no mutational, selective, or gBGC model provides a well-supported explanation. That TAG does increase with G + C usage across eukaryotes makes the usage elsewhere yet more enigmatic. We suggest resolution of the TAG paradox may provide insights into either an unknown but common selective preference (probably at the DNA/RNA level) or an unrecognized complexity to the action of gBGC.


Assuntos
Uso do Códon , Conversão Gênica , Animais , Códon de Terminação , Evolução Molecular , Humanos , Isocoros , Mamíferos/genética , Seleção Genética
3.
Int J Mol Sci ; 23(12)2022 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-35743002

RESUMO

The isochore theory, which was proposed more than 40 years ago, depicts the mammalian genome as a mosaic of long, homogeneous regions that are characterized by their guanine and cytosine (GC) content. The human genome, for instance, was claimed to consist of five compositionally distinct isochore families. The isochore theory, in all its reincarnations, has been repeatedly falsified in the literature, yet isochore proponents have persistently resurrected it by either redefining isochores or by proposing alternative means of testing the theory. Here, I deal with the latest attempt to salvage this seemingly immortal zombie-a sequence segmentation method called isoSegmenter, which was claimed to "identify" isochores while at the same time disregarding the main characteristic attribute of isochores-compositional homogeneity. I used a series of controlled, randomly generated simulated sequences as a benchmark to study the performance of isoSegmenter. The main advantage of using simulated sequences is that, unlike real data, the exact start and stop point of any isochore or homogeneous compositional domain is known. Based on three key performance metrics-sensitivity, precision, and Jaccard similarity index-isoSegmenter was found to be vastly inferior to isoPlotter, a segmentation algorithm with no user input. Moreover, isoSegmenter identified isochores where none exist and failed to identify compositionally homogeneous sequences that were shorter than 100-200 kb. Will this zillionth refutation of "isochores" ensure a final and permanent entombment of the isochore theory? This author is not holding his breath.


Assuntos
Genoma Humano , Isocoros , Algoritmos , Animais , Composição de Bases , Encéfalo , Humanos , Mamíferos/genética
4.
PLoS One ; 17(4): e0267852, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35482795

RESUMO

A new mathematical model is proposed for the analysis of thermo-mechanics effects during isochoric cryopreservation. In that process, some ice crystallization in a fixed-volume container drives pressure elevation, which may be favorable to the preservation of biological material when it resides in the unfrozen portion of the same container. The proposed model is comprehensive, integrating for the first time concepts from the disparate fields of thermodynamics, heat transfer, fluid mechanics, and solid mechanics. The novelty in this study is in treating the cryopreserved material as having a pseudo-viscoelastic behavior over a very narrow temperature range, without affecting the mechanical behavior of the material in the rest of the domain. This unique approach permits treating the domain as a continuum, while avoiding the need to trace freezing fronts and sperate the analysis to liquid and solid subdomains. Consistent with the continuum approach, the heat transfer problem is solved using the enthalpy approach. The presented analysis focusses on isochoric cooling of pure water between standard atmospheric conditions and the triple point of liquid water, ice Ih, and ice III (-22°C and 207.4 MPa). The proposed model is also applicable to isochoric vitrification, by substituting the pseudo-viscoelastic material model with the real viscosity model of the vitrifying material. Results of this study display good agreement with phase-diagram data at steady state, and with experimental data from the literature. Furthermore, this study provides a venue to discussing experimentation aspects of isochoric cryopreservation. The proposed model is further demonstrated on a 3D problem, while discussing scale considerations, crystallization conditions, and transient effects. Notably, the new model can be used to bridge the gap between limited pressure and temperature measurements during cryopreservation and the analysis of the continuum. Arguably, this study presents the most advanced thermo-mechanics model to solve practical problems relating to isochoric cryopreservation.


Assuntos
Gelo , Isocoros , Criopreservação/métodos , Vitrificação , Água
5.
Int J Mol Sci ; 23(7)2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35409128

RESUMO

Double-strand breaks (DSBs) in nuclear DNA represents radiation-induced damage that has been identified as particularly deleterious. Calculating this damage using Monte Carlo track structure modeling could be a suitable indicator to better assess and anticipate the side-effects of radiation therapy. However, as already demonstrated in previous work, the geometrical description of the nucleus and the DNA content used in the simulation significantly influence damage calculations. Therefore, in order to obtain accurate results, this geometry must be as realistic as possible. In this study, a new geometrical model of an endothelial cell nucleus and DNA distribution according to the isochore theory are presented and used in a Monte Carlo simulation chain based on the Geant4-DNA toolkit. In this theory, heterochromatin and euchromatin compaction are distributed along the genome according to five different families (L1, L2, H1, H2, and H3). Each of these families is associated with a different hetero/euchromatin rate related to its compaction level. In order to compare the results with those obtained using a previous nuclear geometry, simulations were performed for protons with linear energy transfers (LETs) of 4.29 keV/µm, 19.51 keV/µm, and 43.25 keV/µm. The organization of the chromatin fibers at different compaction levels linked to isochore families increased the DSB yield by 6-10%, and it allowed the most affected part of the genome to be identified. These new results indicate that the genome core is more radiosensitive than the genome desert, with a 3-8% increase in damage depending on the LET. This work highlights the importance of using realistic distributions of chromatin compaction levels to calculate radio-induced damage using Monte Carlo simulation methods.


Assuntos
Eucromatina , Isocoros , Cromatina , DNA/química , Dano ao DNA , Eucromatina/genética , Humanos , Método de Monte Carlo
6.
Cryobiology ; 106: 91-101, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35337797

RESUMO

Stable aqueous supercooling has shown significant potential as a technique for human tissue preservation, food cold storage, conservation biology, and beyond, but its stochastic nature has made its translation outside the laboratory difficult. In this work, we present an isochoric nucleation detection (INDe) platform for automated, high-throughput characterization of aqueous supercooling at >1 mL volumes, which enables statistically-powerful determination of the temperatures and time periods for which supercooling in a given aqueous system will remain stable. We employ the INDe to investigate the effects of thermodynamic, surface, and chemical parameters on aqueous supercooling, and demonstrate that various simple system modifications can significantly enhance supercooling stability, including isochoric (constant-volume) confinement, hydrophobic container walls, and the addition of even mild concentrations of solute. Finally, in order to enable informed design of stable supercooled biopreservation protocols, we apply a statistical model to estimate stable supercooling durations as a function of temperature and solution chemistry, producing proof-of-concept supercooling stability maps for four common cryoprotective solutes.


Assuntos
Criopreservação , Isocoros , Temperatura Baixa , Criopreservação/métodos , Humanos , Soluções , Água/química
7.
Cryobiology ; 106: 139-147, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35189096

RESUMO

We introduce an isochoric (constant-volume) supercooling cryomicroscope (ISCM), enabling the ice-free study of biological systems and biochemical reactions at subzero temperatures at atmospheric pressure absent ice. This technology draws from thermodynamic findings on the behavior of water in isochoric systems at subfreezing temperatures. A description of the design of the ISCM and a demonstration of the stability of the supercooled solution in the ISCM is followed by an illustration of the possible use of the ISCM in the preservation of biological matter research. A comparison was made between the survival of HeLa cells in the University of Wisconsin (UW) solution in the ISCM at +4 °C under conventional atmospheric conditions and at -5 °C under isochoric supercooled conditions. Continuous real-time monitoring at cryopreservation temperature via fluorescence microscopy showed that after three days of isochoric supercooling storage, the percentage of compromised cells remained similar to fresh controls, while storage at +4 °C yielded approximately three times the mortality rate of cells preserved at -5 °C.


Assuntos
Criopreservação , Isocoros , Criopreservação/métodos , Células HeLa , Humanos , Temperatura , Termodinâmica
8.
Cryo Letters ; 43(4): 189-199, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36626122

RESUMO

There is a developing enthusiasm for discovering new methods, cryoprotectants, systems and devices for cells, tissues, and organ preservation in medicine, in sub-zero temperature conditions and a growing interest in developing more efficient and economical methods for long-term preservation of food in a frozen state. Most of the preservation protocols currently used in medicine and food preservation involve the use of atmospheric pressure, and temperatures lower than normal body temperature in medicine, or lower than room temperature in the food industry. In this state of the art review, we analyzed the results of a new preservation method that uses an isochoric system. We aimed to offer a clear overview of the potential of this new technology. Firstly, to study the origins of isochoric preservation, we searched using the WoS Database. A search with the world "isochoric" returned 488 results. A more specific search of the term isochoric freezing returned 94 results. From these searches, we selected the 12 most relevant articles and discuss them here in detail. We present an overall characterization and criticism of the current use and potential of this new preservation method that can be used in the medicine and food industry. The main findings indicate encouraging results for the tested biological matter, including for the preservation of food products (e.g. cherries, spinach, potatoes), biological organisms (e.g. Caenorhabditis elegans, Escherichia coli, Listeria, Salmonella typhimurium), organs (e.g. rat hearts), tissues (e.g., tilapia fish filets) or cells (e.g., mammalian cells, pancreatic cells). Accordingly, we conclude that the isochoric system holds huge potential as a new technique in the field of preservation. doi.org/10.54680/fr22410110112.


Assuntos
Criopreservação , Isocoros , Ratos , Animais , Criopreservação/métodos , Congelamento , Crioprotetores/farmacologia , Temperatura , Mamíferos
9.
Food Res Int ; 143: 110228, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33992342

RESUMO

This study investigated the potential of isochoric freezing to preserve tomatoes. Isochoric freezing is an emerging technology that preserves biological matter at subfreezing temperatures without any ice damage. Isochoric freezing was compared with freezing under isobaric conditions and with preservation techniques used in the food industry: cold storage at 10 °C and individual quick freezing (IQF). Physicochemical and nutritional properties were evaluated weekly for four weeks. Preservation under isochoric conditions maintained the mass, color, nutrient content (ascorbic acid, lycopene and phenolics) and antioxidant activity of the fresh tomatoes. Also, isochoric preservation led to minimal texture damage. In comparison, mass loss of tomatoes stored at 10 °C for 3 weeks contributed to changes in overall visual quality and firmness as well as significant losses in nutrient content. The greatest mass, texture, and nutrients losses were obtained for tomatoes subjected to IQF and isobaric freezing. The results show that isochoric freezing has the potential to preserve tomatoes while maintaining physicochemical and nutritional properties similar to those of fresh tomatoes which might find application in the commercial preservation of tomatoes.


Assuntos
Vitis , Criopreservação , Congelamento , Isocoros
10.
Cryobiology ; 100: 212-215, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33757760

RESUMO

This paper is a theoretical study of a protocol for transport of high concentrations of cryoprotectants into biological matter, using isochoric freezing. Unlike isobaric freezing, where the entire system freezes at temperatures lower than the freezing temperature, in isochoric freezing a substantial portion of the system remains unfrozen at temperatures below freezing. In isochoric freezing cryopreservation, the system is designed in such a way that the biological matter remains unfrozen and surrounded by an unfrozen solution. The protocol in this study involves the freezing of an isochoric systems along the "liquidus line" at which water and ice are in thermodynamic equilibrium. Rejection of solutes by ice increases the concentration of the solutes in the unfrozen solution surrounding the unfrozen biological matter, leading, thereby, to transport of increasingly higher concentrations of cryoprotectants into the biological matter, as the temperature of the system is lowered and the toxicity of the cryoprotectants is reduced.


Assuntos
Criopreservação , Isocoros , Temperatura Baixa , Criopreservação/métodos , Crioprotetores , Congelamento
11.
Genome Biol Evol ; 12(9): 1573-1578, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32857856

RESUMO

Genomes are characterized by large regions of homogeneous base compositions known as isochores. The latter are divided into GC-poor and GC-rich classes linked to distinct functional and structural properties. Several studies have addressed how isochores shape function and structure. To aid in this important subject, we present IsoXpressor, a tool designed for the analysis of the functional property of transcription within isochores. IsoXpressor allows users to process RNA-Seq data in relation to the isochores, and it can be employed to investigate any biological question of interest for any species. The results presented herein as proof of concept are focused on the preimplantation process in Homo sapiens (human) and Macaca mulatta (rhesus monkey).


Assuntos
Genômica/métodos , Isocoros , Software , Transcrição Genética , Animais , Humanos , Macaca mulatta , Análise de Sequência de RNA
12.
Anim Genet ; 51(3): 358-368, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32069522

RESUMO

Vertebrate genomes are mosaics of megabase-size DNA segments with a fairly homogeneous base composition, called isochores. They are divided into five families characterized by different guanine-cytosine (GC) levels and linked to several functional and structural properties. The increased availability of fully sequenced genomes allows the investigation of isochores in several species, assessing their level of conservation across vertebrate genomes. In this work, we characterized the isochores in Bos taurus using the ARS-UCD1.2 genome version. The comparison of our results with the well-studied human isochores and those of other mammals revealed a large conservation in isochore families, in number, average GC levels and gene density. Exceptions to the established increase in gene density with the increase in isochores (GC%) were observed for the following gene biotypes: tRNA, small nuclear RNA, small nucleolar RNA and pseudogenes that have their maximum number in H2 and H1 isochores. Subsequently, we assessed the ontology of all gene biotypes looking for functional classes that are statistically over- or under-represented in each isochore. Receptor activity and sensory perception pathways were significantly over-represented in L1 and L2 (GC-poor) isochores. This was also validated for the horse genome. Our analysis of housekeeping genes confirmed a preferential localization in GC-rich isochores, as reported in other species. Finally, we assessed the SNP distribution of a bovine high-density SNP chip across the isochores, finding a higher density in the GC-rich families, reflecting a potential bias in the chip, widely used for genetic selection and biodiversity studies.


Assuntos
Bovinos/genética , Citosina/metabolismo , Guanina/metabolismo , Isocoros/genética , Polimorfismo de Nucleotídeo Único , Animais , Análise de Sequência com Séries de Oligonucleotídeos/veterinária
13.
Bioessays ; 41(12): e1900106, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31701567

RESUMO

Recent investigations have revealed 1) that the isochores of the human genome group into two super-families characterized by two different long-range 3D structures, and 2) that these structures, essentially based on the distribution and topology of short sequences, mold primary chromatin domains (and define nucleosome binding). More specifically, GC-poor, gene-poor isochores are low-heterogeneity sequences with oligo-A spikes that mold the lamina-associated domains (LADs), whereas GC-rich, gene-rich isochores are characterized by single or multiple GC peaks that mold the topologically associating domains (TADs). The formation of these "primary TADs" may be followed by extrusion under the action of cohesin and CTCF. Finally, the genomic code, which is responsible for the pervasive encoding and molding of primary chromatin domains (LADs and primary TADs, namely the "gene spaces"/"spatial compartments") resolves the longstanding problems of "non-coding DNA," "junk DNA," and "selfish DNA" leading to a new vision of the genome as shaped by DNA sequences.


Assuntos
Cromatina/metabolismo , DNA/metabolismo , Animais , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , DNA/genética , Genoma Humano/genética , Genômica/métodos , Humanos , Isocoros/metabolismo
14.
Cryo Letters ; 40(1): 51-57, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30955031

RESUMO

BACKGROUND: The use of isochoric containers below the freezing point was proposed for the reduction of freezing damage. OBJECTIVE: To determine mathematically the dielectric constant (k') of a sample inside an isochoric container depending on a suggested nucleated volume, and to compare the values with the reported k' for an isochoric container. METHODS: Different nucleation arrangements inside a cylindrical capacitor filled with water was considered, and the way that ice Ih changes the capacitance and the expected k' was examined. RESULTS: Dielectric constant for different nucleation arrangements decreases proportionally with the nucleated volume, reaching smaller values when the nucleation is supposed only over the internal electrode. However, the nucleation proposed don't reproduce the experimental behavior. CONCLUSION: When compared with experimental results, k' values suggest the water inside an isochoric container remains in liquid state (-4 ~ 0 degree C), which may explain that there is no biological damage for this temperature range.


Assuntos
Criopreservação/instrumentação , Isocoros , Esterilização , Congelamento , Gelo , Água
15.
Cryo Letters ; 40(1): 64-70, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30955033

RESUMO

BACKGROUND: Isochoric freezing systems enable ice-free preservation of biological matter at subfreezing temperatures under the increased hydrostatic pressure. OBJECTIVE: To examine the effects of pressure and exposure period on rat hearts preserved in an isochoric chamber. MATERIALS AND METHODS: Rat hearts were preserved in the UW solution in isochoric chambers at temperatures from -2°C to -8°C and pressure from the atmospheric level to 78 MPa for up to eight hours, with and without the addition of glycerol. Hearts were evaluated via Langendorff perfusion and HE histology. RESULTS: Hearts were compromised quickly as pressure increased, suggesting an acute time-pressure sensitivity. With the addition of 1 M glycerol, which reduces the pressure experienced at a given temperature, the survival time at -4°C was doubled. CONCLUSION: The enhanced hydrostatic pressure encountered during isochoric preservation yields time-dependent negative effects on the heart, which can potentially be alleviated by the addition of a cryoprotectant.


Assuntos
Criopreservação/instrumentação , Coração , Isocoros , Soluções para Preservação de Órgãos , Preservação de Órgãos/instrumentação , Adenosina , Alopurinol , Animais , Glutationa , Pressão Hidrostática , Insulina , Rafinose , Ratos , Temperatura
16.
PLoS One ; 14(3): e0213278, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30865674

RESUMO

Recent findings established a link between DNA sequence composition and interphase chromatin architecture and explained the evolutionary conservation of TADs (Topologically Associated Domains) and LADs (Lamina Associated Domains) in mammals. This prompted us to analyse conformation capture and recombination rate data to study the relationship between chromatin architecture and recombination landscape of human and mouse genomes. The results reveal that: (1) low recombination domains and blocks of elevated linkage disequilibrium tend to coincide with TADs and isochores, indicating co-evolving regulatory elements and genes in insulated neighbourhoods; (2) double strand break (DSB) and recombination frequencies increase in the short loops of GC-rich TADs, whereas recombination cold spots are typical of LADs and (3) the binding and loading of proteins, which are critical for DSB and meiotic recombination (SPO11, DMC1, H3K4me3 and PRMD9) are higher in GC-rich TADs. One explanation for these observations is that the occurrence of DSB and recombination in meiotic cells are associated with compositional and epigenetic features (genomic code) that influence DNA stiffness/flexibility and appear to be similar to those guiding the chromatin architecture in the interphase nucleus of pre-leptotene cells.


Assuntos
Cromatina/genética , Cromossomos de Mamíferos/genética , Genômica/métodos , Histonas/genética , Recombinação Homóloga , Meiose , Animais , Cromatina/química , Cromatina/metabolismo , Quebras de DNA de Cadeia Dupla , Humanos , Isocoros , Camundongos
17.
Sci Rep ; 8(1): 17820, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30546029

RESUMO

Recent investigations have shown that isochores are characterized by a 3-D structure which is primarily responsible for the topology of chromatin domains. More precisely, an analysis of human chromosome 21 demonstrated that low-heterogeneity, GC-poor isochores are characterized by the presence of oligo-Adenines that are intrinsically stiff, curved and unfavorable for nucleosome binding. This leads to a structure of the corresponding chromatin domains, the Lamina Associated Domains, or LADs, which is well suited for interaction with the lamina. In contrast, the high-heterogeneity GC-rich isochores are in the form of compositional peaks and valleys characterized by increasing gradients of oligo-Guanines in the peaks and oligo-Adenines in the valleys that lead to increasing nucleosome depletions in the corresponding chromatin domains, the Topological Associating Domains, or TADs. These results encouraged us to investigate in detail the di- and tri-nucleotide profiles of 100 Kb segments of chromosome 21, as well as those of the di- to octa-Adenines and di- to octa-Guanines in some representative regions of the chromosome. The results obtained show that the 3-D structures of isochores and chromatin domains depend not only upon oligo-Adenines and oligo-Guanines but also, to a lower but definite extent, upon the majority of di- and tri-nucleotides. This conclusion has strong implications for the biological role of non-coding sequences.


Assuntos
Cromossomos Humanos Par 21/química , Genoma Humano , Isocoros/química , Isocoros/síntese química , Nucleossomos/química , Humanos
18.
Sci Rep ; 8(1): 17821, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30546050

RESUMO

The general model presented here for the formation of chromatin domains, LADs and TADs, is primarily based on the 3-D structures of the corresponding DNA sequences, the GC-poor and GC-rich isochores. Indeed, the low-heterogeneity GC-poor isochores locally are intrinsically stiff and curved because of the presence of interspersed oligo-Adenines. In contrast, the high-heterogeneity GC-rich isochores are in the shape of peaks characterized by increasing levels of GC and of interspersed oligo-Guanines. In LADs, oligo-Adenines induce local nucleosome depletions leading to structures that are well suited for the attachment to (and embedding in) the lamina. In TADs, the gradients of GC and of oligo-Guanines are responsible for a decreasing nucleosome density, decreasing supercoiling and increasing accessibility. This "moulding step" shapes the "primary TADs" into loops that lack self-interactions, being CTCF/cohesin-free structures. The cohesin complex then binds to the tips of "primary TADs" and slides down the loops, thanks to Nipbl, an essential factor for loading cohesin and for stimulating its ATPase activity and its translocation. This "extruding step" leads to closer contacts and to self-interactions in the loops and stops at the CTCF binding sites located at the base of the loops that are thus closed and insulated.


Assuntos
Proteínas de Ciclo Celular/química , Cromatina/química , Proteínas Cromossômicas não Histona/química , Isocoros/química , Conformação de Ácido Nucleico , Nucleossomos/química , Fator de Ligação a CCCTC/química , Humanos
19.
An. Facultad Med. (Univ. Repúb. Urug., En línea) ; 5(2): 12-28, dic. 2018. tab, graf
Artigo em Espanhol | LILACS, BNUY, UY-BNMED | ID: biblio-1088677

RESUMO

El genoma humano, como el de todos los mamíferos y aves, es un mosaico de isocoros, los que son regiones muy largas de ADN (>>100 kb) que son homogéneas en cuanto a su composición de bases. Los isocoros pueden ser divididos en un pequeño número de familias que cubren un amplio rango de niveles de GC (GC es la relación molar de guanina+citosina en el ADN). En el genoma humano encontramos cinco familias, que (yendo de valores bajos a altos de GC) son L1, L2, H1, H2 y H3. Este tipo de organización tiene importantes consecuencias funcionales, tales como la diferente concentración de genes, su regulación, niveles de transcripción, tasas de recombinación, tiempo de replicación, etc. Además, la existencia de los isocoros lleva a las llamadas "correlaciones composicionales", lo que significa que en la medida en que diferentes secuencias están localizadas en diferentes isocoros, todas sus regiones (exones y sus tres posiciones de los codones, intrones, etc.) cambian su contenido en GC, y como consecuencia, cambian tanto el uso de aminoácidos como de codones sinónimos en cada familia de isocoros. Finalmente, discutimos el origen de estas estructuras en un marco evolutivo.


The human genome, as the genome of all mammals and birds, are mosaic of isochores, which are very long streches (>> 100 kb) of DNA that are homogeneous in base composition. Isochores can be divided in a small number of families that cover a broad range of GC levels (GC is the molar ratio of guanine+cytosine in DNA). In the human genome, we find five families, which are (going from GC- poor to GC- rich) L1, L2, H1, H2 and H3. This organization has important consequences, as is the case of the concentration of genes, their regulation, transcription levels, rate of recombination, time of replication, etc. Furthermore, the existence of isochores has as a consequence the so called "compositional correlations", which means that as long as sequences are placed in different families of isochores, all of their regions (exons and their three codon positions, introns, etc.) change their GC content, and as a consequence, both codon and amino acids usage change in each isochore family. Finally, we discuss the origin of isochores within an evolutioary framework.


O genoma humano, como todos os mamíferos e aves, é um mosaico de isocóricas, que são muito longas regiões de ADN (>> 100 kb) que são homogéneos na sua composição de base. Isóquos podem ser divididos em um pequeno número de famílias que cobrem uma ampla gama de níveis de GC (GC é a razão molar de guanina + citosina no DNA). No genoma humano, encontramos cinco famílias, que (variando de valores baixos a altos de GC) são L1, L2, H1, H2 e H3. Este tipo de organização tem importantes conseqüências funcionais, como a diferente concentração de genes, sua regulação, níveis de transcrição, taxas de recombinação, tempo de replicação, etc. Além disso, a existência de isocóricas portada chamado "correlações de composição", o que significa que, na medida em que diferentes sequências estão localizados em diferentes isocóricas, todas as regiões (exs e três posições de codões, intrs, etc.) mudam seu conteúdo em GC e, como consequência, alteram tanto o uso de aminoácidos quanto de códons sinônimos em cada família de isócoros. Finalmente, discutimos a origem dessas estruturas em uma estrutura evolucionária.


Assuntos
Humanos , Genoma Humano/genética , Isocoros/genética , Composição de Bases , Íntrons/genética
20.
Microb Genom ; 4(5)2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29708484

RESUMO

Although the genome of Trypanosoma cruzi, the causative agent of Chagas disease, was first made available in 2005, with additional strains reported later, the intrinsic genome complexity of this parasite (the abundance of repetitive sequences and genes organized in tandem) has traditionally hindered high-quality genome assembly and annotation. This also limits diverse types of analyses that require high degrees of precision. Long reads generated by third-generation sequencing technologies are particularly suitable to address the challenges associated with T. cruzi's genome since they permit direct determination of the full sequence of large clusters of repetitive sequences without collapsing them. This, in turn, not only allows accurate estimation of gene copy numbers but also circumvents assembly fragmentation. Here, we present the analysis of the genome sequences of two T. cruzi clones: the hybrid TCC (TcVI) and the non-hybrid Dm28c (TcI), determined by PacBio Single Molecular Real-Time (SMRT) technology. The improved assemblies herein obtained permitted us to accurately estimate gene copy numbers, abundance and distribution of repetitive sequences (including satellites and retroelements). We found that the genome of T. cruzi is composed of a 'core compartment' and a 'disruptive compartment' which exhibit opposite GC content and gene composition. Novel tandem and dispersed repetitive sequences were identified, including some located inside coding sequences. Additionally, homologous chromosomes were separately assembled, allowing us to retrieve haplotypes as separate contigs instead of a unique mosaic sequence. Finally, manual annotation of surface multigene families, mucins and trans-sialidases allows now a better overview of these complex groups of genes.


Assuntos
Doença de Chagas/parasitologia , Genoma de Protozoário , Trypanosoma cruzi/genética , Composição de Bases , Mapeamento Cromossômico , Cromossomos/genética , Células Clonais , Variações do Número de Cópias de DNA , Elementos de DNA Transponíveis , DNA de Protozoário/genética , DNA Satélite , Dosagem de Genes , Glicoproteínas/classificação , Glicoproteínas/genética , Haplótipos , Humanos , Isocoros , Mucinas/classificação , Mucinas/genética , Família Multigênica , Neuraminidase/classificação , Neuraminidase/genética , Sequências Repetitivas de Ácido Nucleico , Retroelementos , Sequenciamento Completo do Genoma
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