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Human aging is a gradual and adaptive process characterized by a decrease in the homeostatic response, leading to biochemical and molecular changes that are driven by hallmarks of aging, such as oxidative stress (OxS), chronic inflammation, and telomere shortening. One of the diseases associated with the hallmarks of aging, which has a great impact on functionality and quality of life, is sarcopenia. However, the relationship between telomere length, sarcopenia, and age-related mortality has not been extensively studied. Moderate physical exercise has been shown to have a positive effect on sarcopenia, decreasing OxS and inflammation, and inducing protective effects on telomeric DNA. This results in decreased DNA strand breaks, reduced OxS and IA, and activation of repair pathways. Higher levels of physical activity are associated with an apparent increase in telomere length. This review aims to present the current state of the art of knowledge on the effect of physical exercise on telomeric maintenance and activation of repair mechanisms in sarcopenia. [ABSTRACT FROM AUTHOR]

Abstract Background Some degree of spontaneous recovery is usually observed after stroke. Experimental studies have provided information about molecular mechanisms underlying this recovery. However, the majority of pre-clinical stroke studies are performed in male rodents, and females are not well studied. This is a clear discrepancy when considering the clinical situation. Thus, it is important to include females in the evaluation of recovery mechanisms for future therapeutic strategies. This study aimed to evaluate spontaneous recovery and molecular mechanisms involved in the recovery phase two weeks after stroke in female rats. Methods Transient middle cerebral artery occlusion was induced in female Wistar rats using a filament model. Neurological functions were assessed up to day 14 after stroke. Protein expression of interleukin 10 (IL-10), transforming growth factor (TGF)-β, neuronal specific nuclei protein (NeuN), nestin, tyrosine-protein kinase receptor Tie-2, extracellular signal-regulated kinase (ERK) 1/2, and Akt were evaluated in the peri-infarct and ischemic core compared to contralateral side of the brain at day 14 by western blot. Expression of TGF-β in middle cerebral arteries was evaluated by immunohistochemistry. Results Spontaneous recovery after stroke was observed from day 2 to day 14 and was accompanied by a significantly higher expression of nestin, p-Akt, p-ERK1/2 and TGF-β in ischemic regions compared to contralateral side at day 14. In addition, a significantly higher expression of TGF-β was observed in occluded versus non-occluded middle cerebral arteries. The expression of Tie-2 and IL-10 did not differ between the ischemic and contralateral sides. Conclusion Spontaneous recovery after ischemic stroke in female rats was coincided by a difference observed in the expression of molecular markers. The alteration of these markers might be of importance to address future therapeutic strategies.

Background: Some degree of spontaneous recovery is usually observed after stroke. Experimental studies have provided information about molecular mechanisms underlying this recovery. However, the majority of pre-clinical stroke studies are performed in male rodents, and females are not well studied. This is a clear discrepancy when considering the clinical situation. Thus, it is important to include females in the evaluation of recovery mechanisms for future therapeutic strategies. This study aimed to evaluate spontaneous recovery and molecular mechanisms involved in the recovery phase two weeks after stroke in female rats. Methods: Transient middle cerebral artery occlusion was induced in female Wistar rats using a filament model. Neurological functions were assessed up to day 14 after stroke. Protein expression of interleukin 10 (IL-10), transforming growth factor (TGF)-β, neuronal specific nuclei protein (NeuN), nestin, tyrosine-protein kinase receptor Tie-2, extracellular signal-regulated kinase (ERK) 1/2, and Akt were evaluated in the peri-infarct and ischemic core compared to contralateral side of the brain at day 14 by western blot. Expression of TGF-β in middle cerebral arteries was evaluated by immunohistochemistry. Results: Spontaneous recovery after stroke was observed from day 2 to day 14 and was accompanied by a significantly higher expression of nestin, p-Akt, p-ERK1/2 and TGF-β in ischemic regions compared to contralateral side at day 14. In addition, a significantly higher expression of TGF-β was observed in occluded versus non-occluded middle cerebral arteries. The expression of Tie-2 and IL-10 did not differ between the ischemic and contralateral sides. Conclusion: Spontaneous recovery after ischemic stroke in female rats was coincided by a difference observed in the expression of molecular markers. The alteration of these markers might be of importance to address future therapeutic strategies. [ABSTRACT FROM AUTHOR]

Abstract Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by an alteration in airway epithelial cell functions including barrier function, wound repair mechanisms, mucociliary clearance. The mechanisms leading to epithelial cell dysfunction in nasal polyps (NPs) remain poorly understood. Our hypothesis was that among the inflammatory cytokines involved in NPs, IL-6 could alter epithelial repair mechanisms and mucociliary clearance. The aim of this study was to evaluate the in vitro effects of IL-6 on epithelial repair mechanisms in a wound repair model and on ciliary beating in primary cultures of Human Nasal Epithelial Cells (HNEC). Methods Primary cultures of HNEC taken from 38 patients during surgical procedures for CRSwNP were used in an in vitro model of wound healing. Effects of increasing concentrations of IL-6 (1 ng/mL, 10 ng/mL, and 100 ng/mL) and other ILs (IL-5, IL-9, IL-10) on wound closure kinetics were compared to cultures without IL-modulation. After wound closure, the differentiation process was characterized under basal conditions and after IL supplementation using cytokeratin-14, MUC5AC, and βIV tubulin as immunomarkers of basal, mucus, and ciliated cells, respectively. The ciliated edges of primary cultures were analyzed on IL-6 modulation by digital high-speed video-microscopy to measure: ciliary beating frequency (CBF), ciliary length, relative ciliary density, metachronal wavelength and the ciliary beating efficiency index. Results Our results showed that: (i) IL-6 accelerated airway wound repair in vitro, with a dose–response effect whereas no effect was observed after other ILs-stimulation. After 24 h, 79% of wounded wells with IL6-100 were fully repaired, vs 46% in the IL6-10 group, 28% in the IL6-1 group and 15% in the control group; (ii) specific migration analyses of closed wound at late repair stage (Day 12) showed IL-6 had the highest migration compared with other ILs (iii) The study of the IL-6 effect on ciliary function showed that CBF and metachronal wave increased but without significant modifications of ciliary density, length of cilia and efficiency index. Conclusion The up-regulated epithelial cell proliferation observed in polyps could be induced by IL-6 in the case of prior epithelial damage. IL-6 could be a major cytokine in NP physiopathology.

Human aging is a gradual and adaptive process characterized by a decrease in the homeostatic response, leading to biochemical and molecular changes that are driven by hallmarks of aging, such as oxidative stress (OxS), chronic inflammation, and telomere shortening. One of the diseases associated with the hallmarks of aging, which has a great impact on functionality and quality of life, is sarcopenia. However, the relationship between telomere length, sarcopenia, and age-related mortality has not been extensively studied. Moderate physical exercise has been shown to have a positive effect on sarcopenia, decreasing OxS and inflammation, and inducing protective effects on telomeric DNA. This results in decreased DNA strand breaks, reduced OxS and IA, and activation of repair pathways. Higher levels of physical activity are associated with an apparent increase in telomere length. This review aims to present the current state of the art of knowledge on the effect of physical exercise on telomeric maintenance and activation of repair mechanisms in sarcopenia.

Natural radiation is the major source of human exposure to ionizing radiation. About 52% of the total dose received from the high natural background radiations (HNBR) areas are due to inhalation dose from radon (222Rn)/thoron (220Rn) and their progenies. Hence, we reviewed the biological effects of 222Rn/220Rn and their progenies on lung tissue, and the possible role of lung stem cells in salvaging the damage caused by 222Rn/220Rn and their progenies. We have extensively reviewed articles among several hits obtained in PubMed, Scopus, and Elsevier databases with keywords 'Radon/Thoron' OR Thoron progeny/Radon progeny OR 'Thoron/Radon inhalation and lungs', and proceed for further analysis. Also, databases related to oxidative damage to lung stem cells by radiation and the repair mechanisms involved by the lung stem cells were also included. Based on the existing epidemiological data on radon in residential buildings, we found that evidence exists on the association of radon induced lung carcinogenesis, but the data regarding the role of thoron induced lung damage is very limited and inconclusive. We also found that limited information has been provided based on ecological designs, leading to poor documentation of health statistics, in particular, organ-specific cancer rates. Finally, we tried to elucidate the possible mechanisms of lung injury induced by thoron inhalation and the probable role of lung stem cell toward the redemption of such oxidative damages. Existing epidemiological data on thoron inhalation and associated health outcomes are limited and inconclusive. Further, in vivo experiments, with respect to radon/thoron inhalation dose rate ranges corresponding to the HNBR areas will be helpful in understanding the cellular and molecular effects. [ABSTRACT FROM AUTHOR]

Ever since gene targeting or specific modification of genome sequences in mice was achieved in the early 1980s, the reverse genetic approach of precise editing of any genomic locus has greatly accelerated biomedical research and biotechnology development. In particular, the recent development of the CRISPR/Cas9 system has greatly expedited genetic dissection of 3D genomes. CRISPR gene-editing outcomes result from targeted genome cleavage by ectopic bacterial Cas9 nuclease followed by presumed random ligations via the host double-strand break repair machineries. Recent studies revealed, however, that the CRISPR genome-editing system is precise and predictable because of cohesive Cas9 cleavage of targeting DNA. Here, we synthesize the current understanding of CRISPR DNA fragment-editing mechanisms and recent progress in predictable outcomes from precise genetic engineering of 3D genomes. Specifically, we first briefly describe historical genetic studies leading to CRISPR and 3D genome engineering. We then summarize different types of chromosomal rearrangements by DNA fragment editing. Finally, we review significant progress from precise 1D gene editing toward predictable 3D genome engineering and synthetic biology. The exciting and rapid advances in this emerging field provide new opportunities and challenges to understand or digest 3D genomes. [ABSTRACT FROM AUTHOR]

Cardiac pathologies remain a dominant cause of morbidity and mortality within the community. The drive to develop therapies capable of repairing damaged heart tissue to achieve clinically significant restoration of function has motivated the pursuit of novel approaches such as cell therapy. To this end, evidence of therapeutic benefits achieved by using mesenchymal stem cells (MSCs) has captured considerable interest despite a relative lack of information regarding the mechanisms involved. This narrative review synthesizes and interprets the current literature describing mechanisms by which MSCs can elicit cardiac repair, thereby directing attention to avenues of further inquiry. OVID versions of MEDLINE and EMBASE were searched for studies describing the role of MSCs in mammalian cardiac repair. Additional studies were sourced from the reference lists of relevant articles and other personal files. MSCs elicit cardiac repair in a range of in vitro systems and animal models of diseases such as myocardial infarction and heart failure. Important mechanisms include the preservation of myocardial contractility, the promotion of angiogenesis, and the modulation of fibrosis. Exposing in vitro MSCs to a microenvironment reflective of that encountered in the injured heart seems to potentiate these therapeutic mechanisms. Promising results in animal studies warrant continuation of clinical MSC cardiac therapy studies. Paracrine functions of MSCs seem to be the dominant mechanism of cardiac repair over direct cellular effects. Although integral, the MSC secretome remains poorly defined. In addition, most of the mechanistic data within the literature have been derived from animal MSC research, necessitating more human MSC-based work. [ABSTRACT FROM AUTHOR]

The skin is the most common target organ affected by graft-versus-host disease (GVHD), with severity and response to therapy representing important predictors of patient survival. Although many of the initiating events in GVHD pathogenesis have been defined, less is known about why treatment resistance occurs or why there is often a permanent failure to restore tissue homeostasis. Emerging data suggest that the unique immune microenvironment in the skin is responsible for defining location- and context-specific mechanisms of injury that are distinct from those involved in other target organs. In this review, we address recent advances in our understanding of GVHD biology in the skin and outline the new research themes that will ultimately enable design of precision therapies.

The skin is the most common target organ affected by graft-versus-host disease (GVHD), with severity and response to therapy representing important predictors of patient survival. Although many of the initiating events in GVHD pathogenesis have been defined, less is known about why treatment resistance occurs or why there is often a permanent failure to restore tissue homeostasis. Emerging data suggest that the unique immune microenvironment in the skin is responsible for defining location- and context-specific mechanisms of injury that are distinct from those involved in other target organs. In this review, we address recent advances in our understanding of GVHD biology in the skin and outline the new research themes that will ultimately enable design of precision therapies. [ABSTRACT FROM AUTHOR]

The fact that proteins are the main target of reactive species formed in the cells and extracellular fluids has led to the realization of a great deal of research devoted to revealing the molecular and biological consequences associated with the presence of intermediary protein radicals. This review article describes and comments upon the main chemical pathways involving primary proteic radicals.

Evidence indicates that many forms of fructose-induced metabolic disturbance are associated with oxidative stress and mitochondrial dysfunction. Mitochondria are prominent targets of oxidative damage; however, it is not clear whether mitochondrial DNA (mtDNA) damage and/or its lack of repair are events involved in metabolic disease resulting from a fructose-rich diet. In the present study, we evaluated the degree of oxidative damage to liver mtDNA and its repair, in addition to the state of oxidative stress and antioxidant defense in the liver of rats fed a high-fructose diet. We used male rats feeding on a high-fructose or control diet for eight weeks. Our results showed an increase in mtDNA damage in the liver of rats fed a high-fructose diet and this damage, as evaluated by the expression of DNA polymerase, was not repaired; in addition, the mtDNA copy number was found to be significantly reduced. A reduction in the mtDNA copy number is indicative of impaired mitochondrial biogenesis, as is the finding of a reduction in the expression of genes involved in mitochondrial biogenesis. In conclusion, a fructose-rich diet leads to mitochondrial and mtDNA damage, which consequently may have a role in liver dysfunction and metabolic diseases. [ABSTRACT FROM AUTHOR]

Aims: The adult mammalian heart has poor regenerative capacity. In contrast, the zebrafish heart retains a robust capacity for regeneration into adulthood. These distinct responses are consequences of a differential utilization of evolutionaryconserved gene regulatory networks in the damaged heart. To systematically identify miRNA-dependent networks controlling cardiac repair following injury, we performed comparative gene and miRNA profiling of the cardiac transcriptome in adult mice and zebrafish. Methods and results: Using an integrated approach, we show that 45 miRNA-dependent networks, involved in critical biological pathways, are differentially modulated in the injured zebrafish vs. mouse hearts. We study, more particularly, the miR-26adependent response. Therefore, miR-26a is down-regulated in the fish heart after injury, whereas its expression remains constant in the mouse heart. Targets of miR-26a involve activators of the cell cycle and Ezh2, a component of the polycomb repressive complex 2 (PRC2). Importantly, PRC2 exerts repressive functions on negative regulators of the cell cycle. In cultured neonatal cardiomyocytes, inhibition of miR-26a stimulates, therefore, cardiomyocyte proliferation. Accordingly, miR-26a knockdown prolongs the proliferative window of cardiomyocytes in the post-natal mouse heart. Conclusions: This novel strategy identifies a series of miRNAs and associated pathways, in particular miR-26a, which represent attractive therapeutic targets for inducing repair in the injured heart. [ABSTRACT FROM AUTHOR]

Background: Peptic ulcer bleeding (PUB) is a major cause of upper gastrointestinal bleeding. The effect of omeprazole on mucosal repair is unknown. Aims: We studied the effect of omeprazole, nonsteroidal anti-inflammatory agents, and smoking on PUB. Methods: There were 43 PUB patients who received regular or high dose of omeprazole for 72 h. Biopsies from antrum and corpus were taken before and after treatment. Biopsy samples from 20 celiac disease patients worked as controls. The expression of Ki-67, Bcl-2, COX-2, Hsp27, and Hsp70 was analyzed from patients and controls. Results: Bcl-2 expression in PUB patients was lower than in controls. However, Bcl-2 increased significantly from 5.0 (SD 4.5) to 9.1 % (SD 6.7), p = 0.0004, in the antrum after omeprazole. In univariate analysis, a high omeprazole dose caused a more profound increase in Ki-67 expression in the corpus: 35.3 % (SD 54.8) than a regular dose: −10.1 % (SD 40.6), p = 0.022. In multivariate analysis, Ki-67 decreased significantly in the corpus between the pre- and posttreatment period ( p = 0.011), while a high omeprazole dose ( p = 0.0265), the use of NSAIDs ( p = 0.0208), and smoking ( p = 0.0296) significantly increased Ki-67 expression. Bcl-2 in the corpus increased significantly ( p = 0.0003) after treatment. Conclusions: Our findings suggest that Bcl-2 may be an important factor in the pathogenesis of a peptic ulcer and PUB. In addition, high-dose omeprazole increased the expression of Ki-67, which may enhance the healing process of a peptic ulcer. [ABSTRACT FROM AUTHOR]

The pathophysiology of asthma is complex and involves a number of factors including atopy and bronchial hyperreactivity. A strong body of evidence suggests that structural and functional respiratory epithelial alterations play a crucial role in both development and persistence of this condition. From the onset of symptoms the airways epithelium of asthmatic patients seems to be altered and unable to repair. The interactions between the epithelium and the underlying mesenchyma, which are jointly referred to as the epithelial-mesenchymal trophic unit (EMTU), are thought to result in a self-sustaining damage of the airways and, ultimately, in a chronic inflammatory scenario. A better understanding of the relationship occurring across EMTU, environmental noxae, and factors of susceptibility to epithelial damage is likely to pave the way to future new preventive and therapeutic strategies for this condition. [ABSTRACT FROM AUTHOR]

Abstract: The halophilic archaeon Halococcus hamelinensis was isolated from living stromatolites in Shark Bay, Western Australia, that are known to be exposed to extreme conditions of salinity, desiccation, and UV radiation. Modern stromatolites are considered analogues of very early life on Earth and thus inhabitants of modern stromatolites, and Hcc. hamelinensis in particular, are excellent candidates to examine responses to high UV radiation. This organism was exposed to high dosages (up to 500J/m2) of standard germicidal UVC (254nm) radiation and overall responses such as survival, thymine–thymine cyclobutane pyrimidine dimer formation, and DNA repair have been assessed. Results show that Hcc. hamelinensis is able to survive high UVC radiation dosages and that intact cells give an increased level of DNA protection over purified DNA. The organism was screened for the bacterial-like nucleotide excision repair (NER) genes uvrA, uvrB, uvrC, as well as for the photolyase phr2 gene. All four genes were discovered and changes in the expression levels of those genes during repair in either light or dark were investigated by means of quantitative Real-Time (qRT) PCR. The data obtained and presented in this study show that the uvrA, uvrB, and uvrC genes were up-regulated during both repair conditions. The photolyase phr2 was not induced during dark repair, yet showed a 20-fold increase during repair in light conditions. The data presented is the first molecular study of different repair mechanisms in the genus Halococcus following exposure to high UVC radiation levels. [ABSTRACT FROM AUTHOR]

The high frequency of mitochondrial DNA (mtDNA) mutations in somatic mammalian cells, which is more than two orders of magnitude higher than the mutation frequency of nuclear DNA (nDNA), significantly correlates with development of a variety of mitochondrial diseases (neurodegenerative diseases, cardiomyopathies, type II diabetes mellitus, cancer, etc.). A direct cause—consequence relationship has been established between mtDNA mutations and aging phenotypes in mammals. However, the unclear nature of the high frequency of mtDNA mutations requires a comprehensive consideration of factors that contribute to this phenomenon: oxidative stress, features of structural organization and repair of the mitochondrial genome, ribonucleotide reductase activity, replication errors, mutations of nuclear genes encoding mitochondrial proteins. [ABSTRACT FROM AUTHOR]

Alkylating agents, commonly used for brain tumor therapy, induce DNA and RNA lesions that, if not repaired, drive cells to apoptosis. Thus, cellular mechanisms that are responsible for nucleic acid repair are possibly involved in drug resistance. This work analyzes hABH2 and hABH3, two human Fe(II)-dependent dioxygenases in pediatric brain tumors that are treated with alkylating agents. We analyzed 25 brain tumor samples for hABH2 and hABH3 mutations; a subset of samples was tested for quantitative expression with Real-Time PCR. Sequencing analysis showed two new mutations in two glioma patients, one of hABH2 coding sequence (I141 V) and the other of hABH3 (D189 N). The mutation at codon 189 falls in a crucial region of the protein. All subjects analyzed by Real-Time PCR showed an enhanced expression of the two genes, particularly of hABH2. This is the first study of hABH2 and hABH3 in pediatric brain tumors; further molecular investigations of their mutations and expression may help determine their role in response to chemotherapy. [ABSTRACT FROM AUTHOR]

This article is a contribution to discourse analysis from the viewpoint of recent developments in the study of verbal (im)politeness in the Spanish-speaking world. It analyzes the discourse functions of interrogative allo-repetitions in a corpus of oral Mexican Spanish from the perspective of both their conversational role as repair mechanisms and as linguistic strategies to convey politeness or impoliteness in interaction. The main findings of this research are that interrogative allo-repetitions fulfill different politeness (i.e. face-saving, face-flattering, or face-threatening) strategies depending not only on their conversational function (true vs. fictitious repair mechanisms), but also -- and most importantly -- on the type of verbal interaction and cultural settings in which they take place, as well as the relationship between participants. [ABSTRACT FROM AUTHOR]

Accumulating clinical and experimental evidence indicates that mesenchymal stem cells (MSCs) are promising cell types in the treatment of cardiac dysfunction. They may trigger production of reparative growth factors, replace damaged cells and create an environment that favours endogenous cardiac repair. However, identifying mechanisms which regulate the role of MSCs in cardiac repair is still at work. To achieve the maximal clinical benefits, ex vivo manipulation can further enhance MSC therapeutic potential. This review focuses on the mechanism of MSCs in cardiac repair, with emphasis on ex vivo manipulation. [ABSTRACT FROM AUTHOR]

All living creatures are subject to aging, but our understanding of what governs aging is limited. In the course of a lifetime, with the constant renewal of the organic substance of living creatures errors arise, e.g. in the formation, disposal, and reproduction of DNA, proteins and lipids or in the constant substitution of aging cells in the organs. These errors are recognized and generally counter­balanced by appropriate repair mechanisms. This process is obviously determined partly by environmental influences (e.g. UV radiation, oxidizing influences, thermal shock) and genetic factors (such as the significance of so-called survival genes and gene mutations). In this paper the authors both explain and test the hypothesis that the aging of organs and organisms is the consequence of and not the reason for a progressive weakening of the repair mechanisms throughout life. [ABSTRACT FROM AUTHOR]

This paper investigates the phenomenon of repairs in simultaneous interpreting. Taking an interdisciplinary approach, the paper combines research carried out in psycholinguistics and neurolinguistics on speech production with studies in the pragmatics of speech reception. A principally qualitative method is used in the analysis of a trilingual corpus (English/French/German) of eight professional conference interpreters recorded at four different international conferences. This paper presents eight examples from English into two different A languages: French (5 examples) and German (3 examples). Levelt’s (1983, 1989) nomenclature of repairs in spontaneous speech is slightly amended in order to take the simultaneous interpreting process into account. The results show that interpreters not only repair errors, but take time to attend to their outputs for different reasons. The limited quantitative analysis shows a discrepancy between interpreters. The various dimensions of repair mechanisms highlighted in this paper give us some insights into the interpreter’s mind at work, or the interpreter’s deployment of processing capacities and decision-making processes. [ABSTRACT FROM AUTHOR]

With regard to a future use of tea polyphenols in intervention trials with individuals at high cancer risk, the effects of the tea ingredient (−)-epigallocatechin gallate (EGCG) on poly(ADP-ribose) (PAR) levels and on DNA damage were investigated in human lymphocytes. A dose- and time-dependent elevation of both PAR formation as assessed by quantitative immunofluorescence analysis and DNA damage as assessed by the comet assay were observed after treatment with EGCG at 20, 40 and 80 μM for 10–240 min. Maximum levels of PAR formation and of DNA damage were observed after 10 min at all concentrations tested. Increased PAR levels were still detectable by 240 min in the 40 and 80 μM groups. At the lowest concentration, which is near the physiological peak values found after tea ingestion, PAR formation was not correlated with DNA damage. Here, EGCG led to pronounced PAR levels, whereas the comet assay was almost negative. In contrast, such marked differences in time course and extent of both genotoxicity and PAR formation following EGCG treatment were not detected after γ-irradiation. Our results suggest that the known chemopreventive effects of EGCG, the main constituent of tea, may be partly attributed to an induction of PAR formation. [Copyright &y& Elsevier]

We have isolated a polyubiquitin cDNA from the modified desiccation-tolerant grass Sporobolus stapfianus. This cDNA, along with a commercially available polyclonal ubiquitin antibody, was used to characterize desiccation/rehydrated-associated changes in ubiquitin-mediated protein degradation in S. stapfianus and the fully desiccation-tolerant moss Tortula ruralis. Northern analysis demonstrated that in S. stapfianus leaves two ubiquitin transcripts, of ca. 1.4 and 1.2 kb, accumulated above control levels during drying and rehydration but were barely detectable in desiccated tissue. The peak in rehydration-associated transcript accumulation coincided with a depletion in ubiquitin monomer levels indicating an increase in protein degradation. Analysis of T. ruralis revealed three ubiquitin transcripts of ca. 1.9, 1.3 and 0.65 kb, with only the 1.3 kb transcript level varying in response to drying and rehydration and all transcripts being stable in dried tissue. Western analysis revealed that conjugated ubiquitin, indicative of proteins targeted for removal, was evident in all samples of Sporobolus but detectable only in slow-drying Tortula which also displayed reduced levels of ubiquitin monomer. These results demonstrate that desiccated T. ruralis gametophyte possesses stable ubiquitin transcripts which can be translated upon rehydration enabling rapid initiation of cellular repair through degradation of certain proteins. This is in contrast to S. stapfianus which requires several hours to replenish depleted ubiquitin transcripts. The ubiquitin response to drying and rehydration in evolutionarily diverse systems is characterized, and the role of repair mechanisms such as ubiquitin-mediated protein degradation in desiccation tolerance is assessed. [ABSTRACT FROM AUTHOR]

Ever since gene targeting or specific modification of genome sequences in mice was achieved in the early 1980s, the reverse genetic approach of precise editing of any genomic locus has greatly accelerated biomedical research and biotechnology development. In particular, the recent development of the CRISPR/Cas9 system has greatly expedited genetic dissection of 3D genomes. CRISPR gene-editing outcomes result from targeted genome cleavage by ectopic bacterial Cas9 nuclease followed by presumed random ligations via the host double-strand break repair machineries. Recent studies revealed, however, that the CRISPR genome-editing system is precise and predictable because of cohesive Cas9 cleavage of targeting DNA. Here, we synthesize the current understanding of CRISPR DNA fragment-editing mechanisms and recent progress in predictable outcomes from precise genetic engineering of 3D genomes. Specifically, we first briefly describe historical genetic studies leading to CRISPR and 3D genome engineering. We then summarize different types of chromosomal rearrangements by DNA fragment editing. Finally, we review significant progress from precise 1D gene editing toward predictable 3D genome engineering and synthetic biology. The exciting and rapid advances in this emerging field provide new opportunities and challenges to understand or digest 3D genomes., (© The Author(s) (2020). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.)