Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 119
Filtrar
1.
Oxid Med Cell Longev ; 2021: 9955717, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34650666

RESUMO

Dynamic cytoskeletal rearrangements underlie the changes that occur during cell division in proliferating cells. MICAL2 has been reported to possess reactive oxygen species- (ROS-) generating properties and act as an important regulator of cytoskeletal dynamics. However, whether it plays a role in gastric cancer cell proliferation is not known. In the present study, we found that MICAL2 was highly expressed in gastric cancer tissues, and this high expression level was associated with carcinogenesis and poor overall survival in gastric cancer patients. The knockdown of MICAL2 led to cell cycle arrest in the S phase and attenuated cell proliferation. Concomitant with S-phase arrest, a decrease in CDK6 and cyclin D protein levels was observed. Furthermore, MICAL2 knockdown attenuated intracellular ROS generation, while MICAL2 overexpression led to a decrease in the p-YAP/YAP ratio and promoted YAP nuclear localization and cell proliferation, effects that were reversed by pretreatment with the ROS scavenger N-acetyl-L-cysteine (NAC) and SOD-mimetic drug tempol. We further found that MICAL2 induced Cdc42 activation, and activated Cdc42 mediated the effect of MICAL2 on YAP dephosphorylation and nuclear translocation. Collectively, our results showed that MICAL2 has a promotive effect on gastric cancer cell proliferation through ROS generation and Cdc42 activation, both of which independently contribute to YAP dephosphorylation and its nuclear translocation.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34596551

RESUMO

The combination of diverse data types and analysis tasks in genomics has resulted in the development of a wide range of visualization techniques and tools. However, most existing tools are tailored to a specific problem or data type and offer limited customization, making it challenging to optimize visualizations for new analysis tasks or datasets. To address this challenge, we designed Gosling-a grammar for interactive and scalable genomics data visualization. Gosling balances expressiveness for comprehensive multi-scale genomics data visualizations with accessibility for domain scientists. Our accompanying JavaScript toolkit called Gosling.js provides scalable and interactive rendering. Gosling.js is built on top of an existing platform for web-based genomics data visualization to further simplify the visualization of common genomics data formats. We demonstrate the expressiveness of the grammar through a variety of real-world examples. Furthermore, we show how Gosling supports the design of novel genomics visualizations. An online editor and examples of Gosling.js, its source code, and documentation are available at https://gosling.js.org.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34587068

RESUMO

A growing number of longitudinal cohort studies are generating data with extensive patient observations across multiple timepoints. Such data offers promising opportunities to better understand the progression of diseases. However, these observations are usually treated as general events in existing visual analysis tools. As a result, their capabilities in modeling disease progression are not fully utilized. To fill this gap, we designed and implemented ThreadStates, an interactive visual analytics tool for the exploration of longitudinal patient cohort data. The focus of ThreadStates is to identify the states of disease progression by learning from observation data in a human-in-the-loop manner. We propose a novel Glyph Matrix design and combine it with a scatter plot to enable seamless identification, observation, and refinement of states. The disease progression patterns are then revealed in terms of state transitions using Sankey-based visualizations. We employ sequence clustering techniques to find patient groups with distinctive progression patterns, and to reveal the association between disease progression and patient-level features. The design and development were driven by a requirement analysis and iteratively refined based on feedback from domain experts over the course of a 10-month design study. Case studies and expert interviews demonstrate that ThreadStates can successively summarize disease states, reveal disease progression, and compare patient groups.

4.
Aesthetic Plast Surg ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491414

RESUMO

BACKGROUND: The procerus is the main muscle across the radix that needs to be operated during rhytidectomy, however, it is unclear whether transecting it can morphologically affect the nose. METHODS: A retrospective study of Asian patients who underwent procerus transection during rhytidectomy in our single institution was performed to assess whether the radix profile had any change postoperatively. The procerus was transected at a plane above the nasion. RESULTS: Ninety-four patients were included. All of them were female with an average age of 50.7 ± 5.2 years and a mean follow-up time of 7.8 ± 3.2 months. Twenty-seven (28.7%) had moderate horizontal wrinkles preoperatively, and sixty-seven (71.3%) had severe rhytides. Different degrees of wrinkle improvement were seen on 91 (96.8%) patients, and no improvement occurred to 3 (3.2%) patients after procerus transection. The anthropometric measurements on these patients did not find any significant difference between the preoperative and postoperative nasal heights, radix projections, nasal lengths, or nasofrontal angles (all p >0.05). CONCLUSIONS: Procerus transection primary contributes to wrinkle improvement. The morphological change of the radix following this operation is too subtle to be observed. This conclusion should be further verified on large samples as well as on other ethnic cohorts in a long-term follow-up. LEVEL OF EVIDENCE IV: This journal requires that authors 10 assign a level of evidence to each article. For a full 11 description of these Evidence-Based Medicine ratings, 12 please refer to the Table of Contents or the online 13 Instructions to Authors www.springer.com/00266 .

5.
Artigo em Inglês | MEDLINE | ID: mdl-34570990

RESUMO

To evaluate the effect of intracutaneous pyonex on analgesia and sedation in critically ill patients who underwent mechanical ventilation. A total of 88 critically ill patients were divided into control group and intervention group. Critical-Care Pain Observation Tool (CPOT) and Richmond Agitation and Sedation Scale (RASS) were used to evaluate pain and agitation. The dosage and treatment period of sedative and analgesic drugs in the intervention group were notably lower than the control group (p<0.05). Analgesia compliance time in the intervention group was superior to control group (p<0.05). The shallow sedation compliance rate in the intervention group was significantly higher than the control group (p<0.01). There was significant difference in blood gas analysis before and after treatment between the two groups (p<0.05). After 2 h of sedation and analgesia, heart rate (HR) in the intervention group was lower than control group, but respiratory rate (RR) was higher than the control group (p<0.05). The traditional analgesia and sedation combined with intracutaneous pyonex reduced the total amount and treatment period of sedative and analgesic drugs in critically ill patients throughout the treatment process, while it also decreased the adverse reactions such as blood pressure drops and respiratory depression.

6.
J Craniofac Surg ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34538787

RESUMO

BACKGROUND: Three-dimensional (3D) digital imaging and printing techniques have been popularly applied in microtia reconstruction. However, there is a lack of clinical report of using them to create 3D printed ear subunit models for cartilage framework fabrication. METHODS: A retrospective study of patients who underwent auricle reconstruction with 3D templates was performed. Patients' demography, surgical complications, framework accuracy, and aesthetic outcomes of the reconstructed auricles were analyzed. RESULTS: Twenty cases included in this study. Complications were minor. The average (median) assessing scores for the framework quality and the reconstructed auricle aesthetics were 8.50 (8) and 8.30 (8), respectively. CONCLUSIONS: Our study found that the use of custom-printed tridimensional ear subunit models achieved a relatively high framework precision and gained good outcomes of the reconstructed ears.Level of Evidence: Level IV.

7.
J Craniofac Surg ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34538792

RESUMO

ABSTRACT: Large congenial melanocytic nevus (LCMN) on the head and face can have negative psychological effects on children and possibly also parents. Patients and their families experience prolonged periods of stress during tissue expansion treatment. The purpose of this study was to evaluate the psychological impact of LCMN on children and parents and explore their fluctuations of psychological status during treatment. Psychosocial status was evaluated in 30 children with LCMN on the head and face and a control group of 56 sex- and age-matched children using the Child Behavior Checklist and the Inventory of Subjective Life Quality for Child and Adolescents. The parents of both groups were also evaluated using the Symptom Checklist-90, the Hospital Anxiety and Depression Scale, and the Perceived Stress Scale. Psychological assessments were performed before expander implantation, before lesion resection, and after operation. Results indicated that children with LCMN were more prone to social problems, withdrawal, and aggressive behavior. Furthermore, their psychological problems increased after entering to school. Parents of children with LCMN had high levels of emotional problems and stress. Continuous expansion resulted in the psychosocial status of both children and parents to reach the worst levels during the period before lesion resection. Six months after surgery, most of these psychosocial effects reduced to levels lower than before surgery. Additionally, we identified several risk factors, namely sex, number of operations, being in education, employment status of mother, and family pressures. Large congenial melanocytic nevus on head and face have considerable psychological impact on children and their parents throughout the tissue expansion treatment. This study demonstrates the need for appropriate psychological screening and interventions.

8.
Nucleic Acids Res ; 49(17): 9755-9767, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34403482

RESUMO

Pericentromeric DNA, consisting of high-copy-number tandem repeats and transposable elements, is normally silenced through DNA methylation and histone modifications to maintain chromosomal integrity and stability. Although histone deacetylase 6 (HDA6) has been known to participate in pericentromeric silencing, the mechanism is still yet unclear. Here, using whole genome bisulfite sequencing (WGBS) and chromatin immunoprecipitation-sequencing (ChIP-Seq), we mapped the genome-wide patterns of differential DNA methylation and histone H3 lysine 18 acetylation (H3K18ac) in wild-type and hda6 mutant strains. Results show pericentromeric CHG hypomethylation in hda6 mutants was mediated by DNA demethylases, not by DNA methyltransferases as previously thought. DNA demethylases can recognize H3K18ac mark and then be recruited to the chromatin. Using biochemical assays, we found that HDA6 could function as an 'eraser' enzyme for H3K18ac mark to prevent DNA demethylation. Oxford Nanopore Technology Direct RNA Sequencing (ONT DRS) also revealed that hda6 mutants with H3K18ac accumulation and CHG hypomethylation were shown to have transcriptionally active pericentromeric DNA.

9.
Acta Biochim Biophys Sin (Shanghai) ; 53(9): 1142-1153, 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34369571

RESUMO

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), essential fatty acids for humans and animals, have been reported to play a beneficial role in a variety of inflammatory diseases. In this study, we investigated the inhibitory effects and potential molecular mechanisms of n-3 PUFAs on the inflammatory response in lipopolysaccharide (LPS)-stimulated mammary alveolar cell line (MAC-T). Results showed that n-3 PUFAs could abate LPS-induced secretions of tumor necrosis factor-α, interleukin (IL)-6 and IL-1ß in MAC-T cells through the nuclear transcription factor kappa B (NF-κB) signal pathway. Meanwhile, n-3 PUFA intervention attenuated histopathologic changes of mammary glands, the white blood cell number decrease, and the alkaline phosphatase level decrease in the serum of mice challenged by LPS. Furthermore, n-3 PUFA intervention improved the ecological structure of the flora in terms of the structural disorder of the non-significant dominant flora induced by LPS in mice. Collectively, both in vitro and in vivo experiments revealed that n-3 PUFAs have a positive effect on LPS-induced inflammatory response, which was possibly mediated by the NF-κB signaling pathway and the intestinal microbiota.


Assuntos
Células Epiteliais/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Lipopolissacarídeos/toxicidade , Glândulas Mamárias Animais/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Linhagem Celular Transformada , Citocinas/biossíntese , Células Epiteliais/patologia , Feminino , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Glândulas Mamárias Animais/patologia , Camundongos
10.
Artigo em Inglês | MEDLINE | ID: mdl-34437063

RESUMO

Inspired by the great success of machine learning (ML), researchers have applied ML techniques to visualizations to achieve a better design, development, and evaluation of visualizations. This branch of studies, known as ML4VIS, is gaining increasing research attention in recent years. To successfully adapt ML techniques for visualizations, a structured understanding of the integration of ML4VISis needed. In this paper, we systematically survey 88 ML4VIS studies, aiming to answer two motivating questions:what visualization processes can be assisted by MLandhow ML techniques can be used to solve visualization problemsThis survey reveals seven main processes where the employment of ML techniques can benefit visualizations:Data Processing4VIS, Data-VIS Mapping, InsightCommunication, Style Imitation, VIS Interaction, VIS Reading, and User Profiling. The seven processes are related to existing visualization theoretical models in an ML4VIS pipeline, aiming to illuminate the role of ML-assisted visualization in general visualizations.Meanwhile, the seven processes are mapped into main learning tasks in ML to align the capabilities of ML with the needs in visualization. Current practices and future opportunities of ML4VIS are discussed in the context of the ML4VIS pipeline and the ML-VIS mapping. While more studies are still needed in the area of ML4VIS, we hope this paper can provide a stepping-stone for future exploration. A web-based interactive browser of this survey is available at https://ml4vis.github.io.

11.
J Mol Neurosci ; 71(10): 2126-2133, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34273101

RESUMO

CircRNAs belong to a novel class of noncoding RNAs that are generated by exons of genes by alternative mRNA splicing and involved in pathophysiological processes of ischemic stroke by regulating neuro-inflammation. A total of 982 patients were enrolled in our study for stroke recovery analysis. The aim of our study was to first explore the association between the inflammation-related circRNA polymorphism and functional outcome 3 months after ischemic stroke by using multivariate logistic regression model. Next, we further investigated the role of circRNA polymorphism in predicting stroke recurrence by using Cox proportional hazard regression model. Five circRNA polymorphisms were genotyped by using polymerase chain reaction and ligation detection reaction method. We identified circ-STAT3 (signal transducer and activator of transcription) rs2293152 GG genotype to be associated with poorer recovery 90 days after stroke (OR = 1.452, 95% CI: 1.165-4.362, p = 0.016). After adjusting for confound factors, the association for rs2293152 with 3 months outcome after IS was stronger, suggesting a mechanism that rs2293152 is an independent risk factor for stroke recovery (OR = 2.255, 95% CI: 1.034-2.038, p = 0.031). However, no other circRNA polymorphisms (circ-DLGAP4 rs41274714, circ-TRAF2 rs10870141, circ-ITCH rs10485505, rs4911154) were associated with functional outcome 3 months after stroke in any genetic models. Subgroup analysis revealed that the negative effect of rs2293152 GG genotype was greater in female and older patients, subjects with history of hypertension. Additionally, all the circRNA polymorphisms were not correlated with recurrent risk of ischemic stroke. Our results indicated that circ-STAT3 might be a novel biomarker for predicting functional outcome after stroke and an important contributor to the ischemic stroke recovery.

12.
Life Sci ; 283: 119851, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34324916

RESUMO

Sleep disorders frequently comorbid with several cardiovascular diseases (CVDs), attracting increasing scientific attention and interest. Sleep disorders include insomnia, sleep-disordered breathing, restless legs syndrome, etc. It is well known that inflammation, sympathetic activation, and endothelial dysfunction play critical roles in sleep disorders, all of which are predisposing factors for CVDs. The comorbidity of sleep disorders and CVDs may have a bidirectional relationship. Patients with CVDs may have a high incidence of sleep disorders and vice versa. This review focused on the comorbidity of sleep disorders and CVDs and discussed the potential pathophysiological mechanisms and therapeutic strategies. In addition to the existing mechanisms, this review summarized novel potential mechanisms underlying comorbidities, such as gut microbiota, orexin, and extracellular vesicles, which may provide a theoretical basis for further basic research and clinical investigations on improving therapeutic outcomes.


Assuntos
Doenças Cardiovasculares , Microbioma Gastrointestinal , Transtornos do Sono-Vigília , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/microbiologia , Doenças Cardiovasculares/terapia , Vesículas Extracelulares/metabolismo , Humanos , Orexinas/metabolismo , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/metabolismo , Transtornos do Sono-Vigília/microbiologia , Transtornos do Sono-Vigília/terapia
13.
Bioinformatics ; 37(Suppl_1): i59-i66, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34252935

RESUMO

MOTIVATION: Molecular profiling of patient tumors and liquid biopsies over time with next-generation sequencing technologies and new immuno-profile assays are becoming part of standard research and clinical practice. With the wealth of new longitudinal data, there is a critical need for visualizations for cancer researchers to explore and interpret temporal patterns not just in a single patient but across cohorts. RESULTS: To address this need we developed OncoThreads, a tool for the visualization of longitudinal clinical and cancer genomics and other molecular data in patient cohorts. The tool visualizes patient cohorts as temporal heatmaps and Sankey diagrams that support the interactive exploration and ranking of a wide range of clinical and molecular features. This allows analysts to discover temporal patterns in longitudinal data, such as the impact of mutations on response to a treatment, for example, emergence of resistant clones. We demonstrate the functionality of OncoThreads using a cohort of 23 glioma patients sampled at 2-4 timepoints. AVAILABILITY AND IMPLEMENTATION: Freely available at http://oncothreads.gehlenborglab.org. Implemented in Java Script using the cBioPortal web API as a backend. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Fenômenos Bioquímicos , Neoplasias , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Neoplasias/genética , Software
14.
Artigo em Inglês | MEDLINE | ID: mdl-34204694

RESUMO

Older adults are at a high risk of falling due to age-related degradations in physical fitness. This study aimed to examine the effects of a modified tap dance program (MTD) on ankle function and postural control in older adults. Forty-four healthy older adults (mean age = 64.1 years, with 9 men) were recruited from local communities and were randomly divided into the MTD group and the control (CON) group. The MTD group received 12 weeks of MTD training 3 times per week for 30 min per session. Outcomes were measured using the five times sit-to-stand test (FTSST) for ankle strength, the universal goniometer for ankle range of motion, and the Footscan® to trace the center of pressure. Results revealed significant improvements in FTSST in the MTD group (mean difference = 1.01), plantar flexion (left = 9.10, right = 10.0). In addition, the MTD group displayed significantly more improvements at midtest than the CON group in FTSST (mean difference = 1.51) and plantar flexion (mean difference: left = 6.10; right = 4.5). Therefore, the MTD can be an effective exercise program for ankle function improvement, but it has limited effects on improving postural control among healthy older adults.


Assuntos
Dança , Equilíbrio Postural , Idoso , Tornozelo , Humanos , Masculino , Pessoa de Meia-Idade , Aptidão Física , Amplitude de Movimento Articular
15.
Front Aging Neurosci ; 13: 665114, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122042

RESUMO

Background: Recent studies have reported that homocysteine (Hcy) may play a vital role in the pathogenesis of vascular dementia (VaD) and Alzheimer's disease (AD). Our study explored the relationship between the plasma Hcy and folate levels and the risk of dementia. Methods: We searched Embase, PubMed, and Web of Science for published literature, including case-control studies and prospective cohort studies, and performed a systematic analysis. Results: The results of our meta-analysis, consisting of case-control studies, showed higher levels of Hcy and lower levels of folate in dementia, AD, and VaD patients than those in non-demented controls (for dementia: SMD = 0.812, 95% CI [0.689, 0.936], p = 0.000 for Hcy; SMD = -0.677, 95% CI [-0.828, -0.525], p = 0.000 for folate). AD patients showed significantly lower plasma Hcy levels compared to VaD patients (SMD = -0.278, 95% CI [-0.466, -0.09], p = 0.000). Subgroup analysis revealed that ethnicity, average age, and dementia type had no significant effect on this association. Furthermore, from the analysis of prospective cohort studies, we identified that elevated plasma Hcy levels were associated with an increased risk of dementia, AD, and VaD (RRdementia = 1.22, 95% CI [1.08, 1.36]; RRAD = 1.07, 95% CI [1.04, 1.11]; RRVaD = 1.13, 95% CI [1.04, 1.23]). In addition, every 5 µmol/L increase in the plasma Hcy level was associated with a 9% increased risk of dementia and a 12% increased risk of AD. Conclusion: Hcy and folic acid are potential predictors of the occurrence and development of AD. A better understanding of their function in dementia could provide evidence for clinicians to rationalize clinical intervention strategies.

16.
Sci Total Environ ; 788: 147792, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34134368

RESUMO

Zearalenone (ZEN) is a secondary metabolite, which is mainly produced by Fusarium fungi and exists in various feeds and agricultural products. Recently, an increasing amount of data has shown that ZEN, as an estrogen-like hormone, can have harmful effects on the female reproductive system, especially on oogenesis and folliculogenesis. Breast milk is considered to be the ideal form of nutrition for infants; however, there are some records of contaminants in food, such as mycotoxins, which may be transferred from maternal blood to milk. In this study, we investigated the toxic effects of breast milk on folliculogenesis in offspring following maternal ZEN exposure. Our results showed that maternal ZEN exposure significantly inhibited the process of primordial follicle (PF) assembly and reduced the number of PFs in suckled offspring's ovaries. In addition, RNA-seq analysis showed that RIG-I-like receptor (RLRs) signaling pathways were activated after exposed to ZEN, which increased the expression levels of DNA damage (γ-H2AX, RAD51, and PARP1) and apoptosis related protein (BAX/BCL2 and Caspase-3). Finally, ZEN exposure interfered with follicular development, as evidenced by the reduced percentages of oocyte maturation and embryonic development when the offspring grew to adolescence. It is worth noting that maternal ZEN exposure disrupted the tri-methylation levels of H3K4, H3K9, and H3K27 in the offspring's oocytes. Our results indicated that maternal ZEN exposure affected ovarian development in offspring through the breast milk, which may be detrimental to their reproductive capability in adult life.


Assuntos
Zearalenona , Feminino , Humanos , Exposição Materna , Folículo Ovariano , Ovário , Gravidez , Reprodução , Zearalenona/toxicidade
17.
Sci Total Environ ; 791: 148173, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34118666

RESUMO

The coordinated supply and demand of ecosystem services (ESs) is important for ensuring regional sustainable development. However, research identifying key areas of imbalanced supply and demand of ESs at the urban agglomeration scale is limited. Therefore, in this study, using the Fujian Delta urban agglomeration of China as the research area, based on multi-source data, and analysis tools, such as ArcGIS, ENVI, and GeoDa, we constructed a research framework and indicator system for ESs supply and demand to determine the spatial change law, matching degree, and coupling coordination degree (CCD) of the ESs. On this basis, the key areas of imbalanced supply and demand of ESs were identified, and optimization strategies were proposed. The results showed that (1) there is obvious spatial heterogeneity between ESs supply and demand in the study area, and different degrees of spatial changes occurred with urbanization. Specifically, areas with large changes were concentrated in urban core areas and economic development zones. (2) The matching degree between ESs supply and demand is quite diverse and shows a trend of polarization. Under the influence of urbanization, some cities began facing ESs supply shortages. (3) Overall, the CCD between ESs supply and demand in the study area is in a state of mild incoordination, but with increasing urbanization, some cities have turned into a state of extreme incoordination. Our results indicate that the ESs supply and demand status in some cities at the urban agglomeration scale has become increasingly severe. Therefore, it is necessary to focus on certain "key areas" to formulate optimization strategies. For key areas with "low supply-high demand" and extreme incoordination, the population and land use intensity should be controlled to reduce the ESs demand level. Meanwhile, for key areas with "high supply-low demand" and extreme incoordination, the utilization efficiency of ecological resources should be improved to enhance the ESs supply capacity. The results of this study will help decision-makers optimize the relationship between ESs supply and demand in order to achieve the sustainable development of urban agglomeration.


Assuntos
Conservação dos Recursos Naturais , Ecossistema , China , Cidades , Urbanização
18.
Plant Cell Environ ; 2021 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-34176142

RESUMO

Abscisic acid (ABA) plays an important role in plant adaptation to water deficits, but its role in regulating root growth (primary root elongation and lateral root number) during different drought-phases remains unclear. Here, we exposed wild-type (WT) and ABA-deficient (not) tomato plants to three continuous drought-phases (moderate drying: day 0-21; severe drying: day 22-47 and re-watering: day 48-51). It was found that WT increased primary root growth during moderate drying; maintained more lateral roots, and greater primary root and total root length under severe drying; and produced more roots after re-watering. After RNA-Seq analysis, we found that the auxin-related genes in root showed different expression patterns between WT and not under drying or re-watering. Further, exogenous supply of IAA partially recovered the root growth of ABA-deficient not plants under three continuous drought-phases. Our results suggested that ABA regulation of tomato root growth during soil drying and recovery can involve auxin response.

20.
Proc Natl Acad Sci U S A ; 118(19)2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33947817

RESUMO

DNA damage plays a central role in the cellular pathogenesis of polyglutamine (polyQ) diseases, including Huntington's disease (HD). In this study, we showed that the expression of untranslatable expanded CAG RNA per se induced the cellular DNA damage response pathway. By means of RNA sequencing (RNA-seq), we found that expression of the Nudix hydrolase 16 (NUDT16) gene was down-regulated in mutant CAG RNA-expressing cells. The loss of NUDT16 function results in a misincorporation of damaging nucleotides into DNAs and leads to DNA damage. We showed that small CAG (sCAG) RNAs, species generated from expanded CAG transcripts, hybridize with CUG-containing NUDT16 mRNA and form a CAG-CUG RNA heteroduplex, resulting in gene silencing of NUDT16 and leading to the DNA damage and cellular apoptosis. These results were further validated using expanded CAG RNA-expressing mouse primary neurons and in vivo R6/2 HD transgenic mice. Moreover, we identified a bisamidinium compound, DB213, that interacts specifically with the major groove of the CAG RNA homoduplex and disfavors the CAG-CUG heteroduplex formation. This action subsequently mitigated RNA-induced silencing complex (RISC)-dependent NUDT16 silencing in both in vitro cell and in vivo mouse disease models. After DB213 treatment, DNA damage, apoptosis, and locomotor defects were rescued in HD mice. This work establishes NUDT16 deficiency by CAG repeat RNAs as a pathogenic mechanism of polyQ diseases and as a potential therapeutic direction for HD and other polyQ diseases.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...