RESUMO
Studies on myotonic dystrophy type 1 (DM1) have led to the RNA-mediated disease model for hereditary disorders caused by noncoding microsatellite expansions. This model proposes that DM1 disease manifestations are caused by a reversion to fetal RNA processing patterns in adult tissues due to the expression of toxic CUG RNA expansions (CUGexp) leading to decreased muscleblind-like, but increased CUGBP1/ETR3-like factor 1 (CELF1), alternative splicing activities. Here, we test this model in vivo, using the mouse HSALR poly(CUG) model for DM1 and recombinant adeno-associated virus (rAAV)-mediated transduction of specific splicing factors. Surprisingly, systemic overexpression of HNRNPA1, not previously linked to DM1, also shifted DM1-relevant splicing targets to fetal isoforms, resulting in more severe muscle weakness/myopathy as early as 4 to 6 wk posttransduction, whereas rAAV controls were unaffected. Overexpression of HNRNPA1 promotes fetal exon inclusion of representative DM1-relevant splicing targets in differentiated myoblasts, and HITS-CLIP of rAAV-mycHnrnpa1-injected muscle revealed direct interactions of HNRNPA1 with these targets in vivo. Similar to CELF1, HNRNPA1 protein levels decrease during postnatal development, but are elevated in both regenerating mouse muscle and DM1 skeletal muscle. Our studies suggest that CUGexp RNA triggers abnormal expression of multiple nuclear RNA binding proteins, including CELF1 and HNRNPA1, that antagonize MBNL activity to promote fetal splicing patterns.
Assuntos
Processamento Alternativo , Ribonucleoproteína Nuclear Heterogênea A1/genética , Ribonucleoproteína Nuclear Heterogênea A1/metabolismo , Distrofia Miotônica/genética , Animais , Proteínas CELF1/genética , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Feto , Humanos , Camundongos , Camundongos Transgênicos , Distrofia Miotônica/metabolismo , Distrofia Miotônica/patologia , Proteínas de Ligação a RNA/metabolismoRESUMO
OBJECTIVE: To explore the electromyography (EMG) and nerve conduction (NC) features of patients with myotonic dystrophy type 1 (DM1). METHODS: Routine PCR and triplet primed-PCR (TP-PCR) were performed for 33 clinically diagnosed DM1 cases at our clinic from June 2009 to June 2012. The EMG and NC results of 30 patients with a genetic diagnosis of DM1 were collected and analyzed. RESULTS: Myotonic discharges were found in all patients and EMG revealed myogenic changes in 29 patients. Among all 123 muscles examined, the incidence of myotonic discharges was, a little higher than that of myogenic changes (91.87% vs 90.24%). The rate of myotonic discharges in distal muscles was higher than that of myotonic discharges in proximal muscles (100% vs 83.61%). And the difference was statistically significant. No difference existed in myogenic changes between distal and proximal muscles.(87.10% vs 93.44%) Nerve conduction was all normal. CONCLUSIONS: Myotonic discharges and myogenic changes are important EMG features in DM1. In early stage of DM1, myotonic discharges may be the isolated EMG abnormality. Myotonic discharges are predominantly detected in distal muscles. The involved regions detected by EMG are wider than those of clinical findings. EMG is an important screening tool for subclinical or early atypical DM1 patients.
Assuntos
Músculo Esquelético/fisiopatologia , Distrofia Miotônica/fisiopatologia , Adolescente , Adulto , Idoso , Eletromiografia , Fenômenos Eletrofisiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Distrofia Miotônica/diagnóstico , Adulto JovemRESUMO
To investigate the response mechanisms of soil bacterial and fungal communities to the changes of preci-pitation in a desert steppe of Ningxia, we conducted a three-year precipitation control experiment following completely randomized design. There were five treatments, natural precipitation (T0), 50% less in precipitation (T1), 25% less in precipitation (T2), 25% more in precipitation (T3) and 50% more in precipitation (T4). By using Illumina high-throughput sequencing and bioinformatics analysis, we investigated the effects of increased and decreased precipitation on soil bacterial and fungal communities, and examined the correlations between soil physicochemical properties, plant communities and soil bacterial and fungal communities. The result showed that the richness of soil bacteria and fungi was highest in the T4 treatment. In addition, the relative abundance of Chloroflexi, the predominant phyla of soil bacteria was more sensitive to precipitation change. However, the relative abundance of only Ascomycota, a rare fungal taxon, responded to precipitation changes. Results of redundancy analysis showed that the first two axes accounted for 92.8% and 87.4% of the total variance for soil bacterial and fungal community composition, respectively. Precipitation and soil pH were the most important environmental factors driving changes in soil bacterial diversity and community composition. On the one hand, precipitation had a direct positive effect on bacterial diversity and community composition. On the other hand, precipitation changed pH by affecting soil moisture, which in turn had a significant indirect effect on bacterial diversity and community composition. Plant community biomass, plant species richness, and soil pH were the most influential environmental factors affecting fungal diversity and community composition. Precipitation had no direct effect on soil fungal community, but had a significant indirect effect by changing plant community richness and soil pH. The response mechanisms of bacterial and fungal communities in soil differed significantly under different precipitation regimes in the desert grasslands of Ningxia.
Assuntos
Micobioma , Bactérias , Biomassa , Sequenciamento de Nucleotídeos em Larga Escala , SoloRESUMO
In recent years, the number of sequencing data of plant whole genome have been increasing rapidly and the whole genome sequencing has been also performed widely in woody plants. However, there are a set of obstacles in investigating the whole genome sequencing in woody plants, which include larger genome, complex genome structure, limitations of assembly, annotation, functional analysis, and restriction of the funds for scientific research. Therefore, to promote the efficiency of the whole genome sequencing in woody plants, the development and defect of this field should be analyzed. The three-generation sequencing technologies (i.e., Sanger sequencing, synthesis sequencing, and single molecule sequencing) were compared in our studies. The progress mainly focused on the whole genome sequencing in four woody plants (Populus, Grapevine, Papaya, and Apple), and the application of sequencing results also was analyzed. The future of whole genome sequencing research in woody plants, consisting of material selection, establishment of genetic map and physical map, selection of sequencing technology, bioinformatic analysis, and application of sequencing results, was discussed.
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Genoma de Planta , Análise de Sequência de DNA/métodos , Árvores/genética , Caricaceae/genética , Rosácea/genética , Vitis/genéticaRESUMO
We measured the total vegetation carbon stock in the widely distributed natural grassland of meadow steppe (MS), warm steppe (WS), steppe desert (SD) and desert steppe (DS)] in Ningxia, using survey and sampling method. The results showed that the average carbon rate of vege-tation, shrubs and root were 0.40, and that of litter was 0.39. The total vegetation carbon density of meadow steppe, warm steppe, steppe desert and desert steppe (including aboveground vegetation, litter and roots) was 470.26, 192.23, 117.17 and 83.36 g·m-2, while that of aboveground vegetation was 87.35, 68.50, 59.32 and 40.05 g·m-2, and that of roots was 344.29, 108.83, 50.65 and 30.29 g·m-2, litter carbon storage was 38.62,14.91, 7.19 and 13.03 g·m-2, respectively. The order of those grassland types ranked as MSï¼WSï¼SDï¼DS. Root carbon storage contributed the most to carbon storage in meadow steppe and warm steppe, and aboveground vegetation carbon storage contributed the most to steppe desert and desert steppe. Root carbon storage showed a decreasing trend with the increases of soil depth within 40 cm soil layer. For the spatial distribution of total carbon stock, the southern part of meadow steppe and temperate steppe had obviously higher carbon stock than the middle and north part of desert steppe and steppe desert.
Assuntos
Carbono , Pradaria , Carbono/análise , China , SoloRESUMO
Spastic paraplegias (SPGs) are a group of clinically and genetically heterogeneous neurodegenerative diseases. Mutations in 78 genes have been identified in autosomal dominant hereditary SPG (AD-HSP) and autosomal recessive hereditary SPG (AR-HSP). Compared to familial HSP, much less is known about the genetic and clinical profiles of sporadic SPGs. In this study, we have screened mutations for 18 sporadic SPGs or AR-HSP patients (mainly Northern Chinese) by whole-exome sequencing. We identified 12 mutations in five genes in 9 (50%) patients, including 9 novel ones: SPG5A/CYP7B1 (c.851C > A; c.122 + 2 T > G), SPG11/KIAA1840 (c.1735 + 3_ 1735 + 6del AAGT); SPG7/SPG7 (c.1454G > A; c.1892_ 1906dup GAGGACGGGCCTCGG); SPG39/PNPLA6 (c.1591G > A; c. 2990C > T); SPG15/ ZFYVE26 (c. 4804C > T; c. 4278 G > A). Among all the mutations, 7 were detected in the SPG5A and SPG11. Age at onset was significantly younger in cases with mutations (15.45 ± 6.78 years) than those without mutations (25.56 ± 10.90 years) (P = 0.03). Except for two cases with the SPG5A mutations, all cases presented with complicated SPGs. Three cases carrying mutations in SPG7, SPG15, SPG39 showed symptoms and signs of ataxia. One case carrying the homozygous c.259 + 2 T > C mutation in CYP7B1 showed serum parameters indicating liver impairment. Magnetic resonance imaging showed significantly thinned corpus callosum in cases with SPG11 and SPG15, but not in those with SPG5A, SPG7 or SPG39. In contrast, cerebellar atrophy was prominent in the SPG7 and SPG39 cases. These findings expand the spectrum of genetic, clinical and imaging features of sporadic SPG and AR-HSP, and have important implications in genetic counselling, molecular mechanisms and precise diagnosis of the disease.
Assuntos
Taxa de Mutação , Paraplegia Espástica Hereditária/genética , Adolescente , Adulto , Cerebelo/diagnóstico por imagem , Corpo Caloso/diagnóstico por imagem , Família 7 do Citocromo P450/genética , Feminino , Humanos , Fígado/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Proteínas/genética , Paraplegia Espástica Hereditária/diagnóstico por imagem , Paraplegia Espástica Hereditária/patologia , Esteroide Hidroxilases/genéticaRESUMO
OBJECTIVE: To observe the clinical effect of high suspension and low incision (HSLI) surgery on mixed haemorrhoids, compared with Milligan-Morgan haemorrhoidectomy. METHODS: A multi-centre, randomized, single-blind, non-inferiority clinical trial was performed. Participants with mixed haemorrhoids from Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing Rectum Hospital, Air Force Medical Center of People's Liberation Army of China, and Puyang Hospital of Traditional Chinese Medicine were enrolled from September 2016 to March 2018. By using a blocked randomization scheme, participants were assigned to two groups. The experimental group was treated with HSLI, while the control group was treated with Milligan-Morgan haemorrhoidectomy. The primary outcome was the clinical effect evaluated at 12 weeks after operation. The secondary outcomes included the number of haemorrhoids treated during the operation, pain scores, use of analgesics, postoperative oedema, wound healing, incidence of anal stenosis, anorectal manometry after operation, as well as surgical duration, length of stay and total hospitalization expenses. A safety evaluation was also conducted. RESULTS: In total, 246 eligible participants were enrolled, with 123 cases in each group. There was no significant difference in the clinical effect between the two groups (100.00% vs. 99.19%, P>0.05). Compared with the control group, the number of external haemorrhoids treated during the operation and the pain scores after operation were significantly reduced in the experimental group (P<0.05 or P<0.01); the patient number with wound healing at 2 weeks after operation and the functional length of anal canal at 12 weeks after operation were significantly increased in the experimental group (P<0.05). There was no significant difference in the incidence of anal stenosis, the numbers of patients using analgesics and patients with postoperative oedema between the two groups after operation (P>0.05). The surgical duration and length of stay in the experimental group were significantly longer than those in the control group, and the total hospitalization expense was significantly higher than that in the control group (all P<0.05). No adverse events were reported in either group during the whole trial or follow-up period. CONCLUSION: HSLI had the advantages of preserving the skin of anal canal completely, alleviating postsurgical pain and promoting rapid recovery after operation. (Registration No. ChiCTR1900022883).
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório , Hemorroidas , Hemorroidas/cirurgia , Humanos , Ligadura , Medicina Tradicional Chinesa , Método Simples-Cego , Resultado do TratamentoRESUMO
To accurately estimate ecosystem carbon storage of natural grassland in Ningxia, we examined ecosystem carbon storage in four types of typical temperate natural grasslands, including meadow steppe, warm steppe, steppe desert, and desert steppe in Ningxia. The results showed that the total vegetation biomass of meadow steppe, warm steppe, steppe desert and desert steppe were 1178.91, 481.22, 292.80 and 209.09 g·m-2, respectively. Root biomass was the main component of total vegetation biomass of meadow steppe and warm steppe, with a contribution of 73.1% and 56.6%, respectively. Aboveground biomass was the main component of total vegetation biomass of steppe desert and desert steppe, accounting for 50.3% and 47.6%, respectively. Litter made low contribution, being 8.5%, 8.0%, 6.4% and 16.2%, respectively. Ecosystem carbon storage of four typical natural grassland was 13.90, 5.94, 2.69 and 2.37 kg·m-2, vegetation carbon storage was 470.26, 192.23, 117.17 and 83.36 g·m-2, and soil organic carbon storage in 0-40 cm layers were 13.43, 5.75, 2.58 and 2.29 kg·m-2, respectively. Soil organic carbon storage was the main body of the total carbon storage of four typical natural grassland in Ningxia, accounting for 96.6%, 96.8%, 95.6% and 96.5%, respectively. The total vegetation biomass, vegetation carbon storage, soil organic carbon storage and ecosystem carbon storage of four natural grassland types were in the order of meadow steppeï¼warm steppeï¼steppe desertï¼desert steppe.