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1.
J Mol Biol ; 433(7): 166846, 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33549587

RESUMO

Chromosome ends are protected by guanosine-rich telomere DNA that forms stable G-quadruplex (G4) structures. The heterodimeric POT1-TPP1 complex interacts specifically with telomere DNA to shield it from illicit DNA damage repair and to resolve secondary structure that impedes telomere extension. The mechanism by which POT1-TPP1 accomplishes these tasks is poorly understood. Here, we establish the kinetic framework for POT1-TPP1 binding and unfolding of telomere G4 DNA. Our data identify two modes of POT1-TPP1 destabilization of G4 DNA that are governed by protein concentration. At low concentrations, POT1-TPP1 passively captures transiently unfolded G4s. At higher concentrations, POT1-TPP1 proteins bind to G4s to actively destabilize the DNA structures. Cancer-associated POT1-TPP1 mutations impair multiple reaction steps in this process, resulting in less efficient destabilization of G4 structures. The mechanistic insight highlights the importance of cell cycle dependent expression and localization of the POT1-TPP1 complex and distinguishes diverse functions of this complex in telomere maintenance.

2.
New Phytol ; 230(3): 1063-1077, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33474772

RESUMO

Plant hormones can adjust the physiology and development of plants to enhance their adaptation to biotic and abiotic challenges. Jasmonic acid (JA), one of the immunity hormones in plants, triggers genome-wide transcriptional changes in response to insect attack and wounding. Although JA is known to affect the development of trichomes, epidermal appendages that form a protective barrier against various stresses, it remains unclear how JA interacts with developmental programs that regulate trichome development. In this study, we show that JA affects trichome length in tomato by releasing the transcriptional repression mediated by Jasmonate ZIM (JAZ) proteins. We identified SlJAZ4, a negative regulator preferentially expressed in trichomes, as the critical component in JA signaling in tomato trichomes. We also identified a homeodomain-leucine zipper gene, SlHD8, as the downstream regulator of JA signaling that promotes trichome elongation. SlHD8 is also highly expressed in trichomes and physically interacts with SlJAZ4. Loss-of-function mutations in SlHD8 caused shorter trichomes, a phenotype that was only partially rescued by methyl jasmonate treatment. Our dual-luciferase and chromatin immunoprecipitation-quantitative PCR assays revealed that SlHD8 regulates trichome elongation by directly binding to the promoters of a set of cell-wall-loosening protein genes and activating their transcription. Together, our findings define SlHD8-SlJAZ4 as a key module mediating JA-induced trichome elongation in tomato.

3.
Int J Mol Sci ; 22(2)2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33466786

RESUMO

Glycerol-3-phosphate acyltransferases (GPATs) play an important role in glycerolipid biosynthesis, and are mainly involved in oil production, flower development, and stress response. However, their roles in regulating plant height remain unreported. Here, we report that Arabidopsis GPAT1 is involved in the regulation of plant height. GUS assay and qRT-PCR analysis in Arabidopsis showed that GPAT1 is highly expressed in flowers, siliques, and seeds. A loss of function mutation in GPAT1 was shown to decrease seed yield but increase plant height through enhanced cell length. Transcriptomic and qRT-PCR data revealed that the expression levels of genes related to gibberellin (GA) biosynthesis and signaling, as well as those of cell wall organization and biogenesis, were significantly upregulated. These led to cell length elongation, and thus, an increase in plant height. Together, our data suggest that knockout of GPAT1 impairs glycerolipid metabolism in Arabidopsis, leading to reduced seed yield, but promotes the biosynthesis of GA, which ultimately enhances plant height. This study provides new evidence on the interplay between lipid and hormone metabolism in the regulation of plant height.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Glicerol-3-Fosfato O-Aciltransferase/genética , Mutação , Óleos Vegetais/metabolismo , Caules de Planta/genética , Sementes/genética , Arabidopsis/citologia , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Forma Celular/genética , Flores/genética , Flores/metabolismo , Perfilação da Expressão Gênica/métodos , Regulação Enzimológica da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Ontologia Genética , Glicerol-3-Fosfato O-Aciltransferase/metabolismo , Caules de Planta/citologia , Caules de Planta/metabolismo , Plantas Geneticamente Modificadas , Sementes/metabolismo
4.
J Speech Lang Hear Res ; : 1-11, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33166243

RESUMO

Purpose We aimed to compare the speech of parents and examiners as they elicited language samples from minimally and low-verbal (MLV) children and adolescents with autism spectrum disorder (ASD), while following the same semi-structured elicitation protocol, Eliciting Language Samples for Analysis-Adolescents (ELSA-A). We also compared the speech elicited from the MLV children/adolescents by their parents at home and by trained examiners in the lab and assessed the feasibility of parents collecting language samples at home. Method Thirty-three (five female, 28 male) MLV children and adolescents with ASD between the ages of 6;6 and 19;7 (years;months) participated. All participants were administered standardized assessments, and a trained examiner collected an ELSA-A language sample from them in the lab. The parents of 22 of the children/adolescents collected an ELSA-A sample at home. All language samples were transcribed following standard procedures, and measures of expressive language were extracted to assess the quantity of speech, its syntactic complexity, and lexical diversity. At the end of the study, parents filled out a feedback survey about their experiences collecting ELSA-A. Results On average, parents produced twice as much speech as trained examiners during ELSA-A. However, their speech did not differ in syntactic complexity or lexical diversity. When with their parents, the MLV children/adolescents also produced twice as much speech than with trained examiners. In addition, their samples were more lexically diverse. Overall, parents elicited longer language samples but administered fewer of the ELSA-A activities. Nevertheless, the majority of parents rated the experience of collecting language samples at home favorably. Conclusions When parents collect language samples at home, their older MLV children/adolescents with ASD produce more speech and engage in more back-and-forth verbal interactions than when with trained examiners. Because parent-elicited language samples allow for a richer assessment of children's expressive language abilities, future studies should focus on identifying ways to encourage parents to collect data at home.

5.
Virol Sin ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32955691

RESUMO

In the original version of Fig. 4I and 4J, the cutoff lines were accidently shifted during figure layout. Figures 4I and 4J are re-drawn and provided below.

6.
Autism Res ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32909382

RESUMO

Expressive language and communication are among the key targets of interventions for individuals with autism spectrum disorder (ASD), and natural language samples provide an optimal approach for their assessment. Currently, there are no protocols for collecting such samples that cover a wide range of ages or language abilities, particularly for children/adolescents who have very limited spoken language. We introduce a new protocol for collecting language samples, eliciting language samples for analysis (ELSA), and a novel approach for deriving basic measures of verbal communicative competence from it that bypasses the need for time-consuming transcription. Study 1 presents ELSA-adolescents (ELSA-A), designed for minimally and low-verbal older children/adolescents with ASD. The protocol successfully engaged and elicited speech from 46 participants across a wide range of ages (6;6-19;7) with samples averaging 20-25 min. The collected samples were segmented into speaker utterances (examiner and participant) using real-time coding as one is listening to the audio recording and two measures were derived: frequency of utterances and conversational turns per minute. These measures were shown to be reliable and valid. For Study 2, ELSA was adapted for younger children (ELSA-Toddler [ELSA-T]) with samples averaging 29 min from 19 toddlers (2;8-4;10 years) with ASD. Again, measures of frequency of utterances and conversational turns derived from ELSA-T were shown to have strong psychometric properties. In Study 3, we found that ELSA-A and ELSA-T were equivalent in eliciting language from 17 children with ASD (ages: 4;0-6;8), demonstrating their suitability for deriving robust objective assessments of expressive language that could be used to track change in ability over time. We introduce a new protocol for collecting expressive language samples, ELSA, that can be used with a wide age range, from toddlers (ELSA-T) to older adolescents (ELSA-A) with ASD who have minimal or low-verbal abilities. The measures of language and communication derived from them, frequency of utterances, and conversational turns per minute, using real-time coding methods, can be used to characterize ability and chart change in intervention research. LAY SUMMARY: We introduce a new protocol for collecting expressive language samples, ELSA, that can be used with a wide age range, from toddlers (ELSA-T) to older adolescents (ELSA-A) with autism spectrum disorder who have minimal or low-verbal abilities. The measures of language and communication derived from them, frequency of utterances and conversational turns per minute, using real-time coding methods, can be used to characterize ability and chart change in intervention research.

7.
Talanta ; 220: 121388, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32928410

RESUMO

In this work, an assay with high sensitivity and selectivity for the detection of formaldehyde (FA) is presented. The assay applied a gold nanoprism/Tollens' reagent (Au-np/TR) complex as the sensor used in headspace single-drop microextraction (HS-SDME). A surface plasmon resonance signal enhancement as well as color change was caused by the formation of Au@Ag-np after a redox reaction between FA and TR during the HS-SDME process. With the utilization of smartphone nanocolorimetry (SNC), the FA could be detected and quantified. For HS-SDME-SNC, a linearity calibration curve ranging from 0.1 to 100 µM was obtained, and the limit of detection was determined to be 30 nM. Successful attempts to determine FA were demonstrated by analysis of the analyte in (adulterated) raw food samples (octopus and chicken flesh). Matrix effects from real samples were avoided by using HS-SDME, and only a 3-µL droplet of solvent was needed in the assay.

8.
Nat Biomed Eng ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958897

RESUMO

The clinical applicability of porcine xenotransplantation-a long-investigated alternative to the scarce availability of human organs for patients with organ failure-is limited by molecular incompatibilities between the immune systems of pigs and humans as well as by the risk of transmitting porcine endogenous retroviruses (PERVs). We recently showed the production of pigs with genomically inactivated PERVs. Here, using a combination of CRISPR-Cas9 and transposon technologies, we show that pigs with all PERVs inactivated can also be genetically engineered to eliminate three xenoantigens and to express nine human transgenes that enhance the pigs' immunological compatibility and blood-coagulation compatibility with humans. The engineered pigs exhibit normal physiology, fertility and germline transmission of the 13 genes and 42 alleles edited. Using in vitro assays, we show that cells from the engineered pigs are resistant to human humoral rejection, cell-mediated damage and pathogenesis associated with dysregulated coagulation. The extensive genome engineering of pigs for greater compatibility with the human immune system may eventually enable safe and effective porcine xenotransplantation.

9.
Virol Sin ; 2020 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-32749593

RESUMO

Reverse transcription-polymerase chain reaction (RT-PCR) is an essential method for specific diagnosis of SARS-CoV-2 infection. Unfortunately, false negative test results are often reported. In this study, we attempted to determine the principal causes leading to false negative results of RT-PCR detection of SARS-CoV-2 RNAs in respiratory tract specimens. Multiple sputum and throat swab specimens from 161 confirmed COVID-19 patients were tested with a commercial fluorescent RT-PCR kit targeting the ORF1ab and N regions of SARS-CoV-2 genome. The RNA level of a cellular housekeeping gene ribonuclease P/MRP subunit p30 (RPP30) in these specimens was also assessed by RT-PCR. Data for a total of 1052 samples were retrospectively re-analyzed and a strong association between positive results in SARS-CoV-2 RNA tests and high level of RPP30 RNA in respiratory tract specimens was revealed. By using the ROC-AUC analysis, we identified Ct cutoff values for RPP30 RT-PCR which predicted false negative results for SARS-CoV-2 RT-PCR with high sensitivity (95.03%-95.26%) and specificity (83.72%-98.55%) for respective combination of specimen type and amplification reaction. Using these Ct cutoff values, false negative results could be reliably identified. Therefore, the presence of cellular materials, likely infected host cells, are essential for correct SARS-CoV-2 RNA detection by RT-PCR in patient specimens. RPP30 could serve as an indicator for cellular content, or a surrogate indicator for specimen quality. In addition, our results demonstrated that false negativity accounted for a vast majority of contradicting results in SARS-CoV-2 RNA test by RT-PCR.

10.
Med Microbiol Immunol ; 209(6): 657-668, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32860073

RESUMO

The magnitude of SARS-CoV-2 infection, the dynamic changes of immune parameters in patients with the novel coronavirus disease (COVID-19) and their correlation with the disease severity remain unclear. The clinical and laboratory results from 154 confirmed COVID-19 patients were collected. The SARS-CoV-2 RNA levels in patients were estimated using the Ct values of specific RT-PCR tests. The lymphocyte subsets and cytokine profiles in the peripheral blood were analyzed by flow cytometry and specific immunoassays. 154 confirmed COVID-19 patients were clinically examined up to 4 weeks after admission. The initial SARS-CoV-2 RNA Ct values at admission varied, but were comparable in the patient groups classified according to the age, gender, underlying diseases, and disease severity. Three days after admission, significant higher Ct values were found in severe cases. Significantly reduced counts of T cells and T cell subsets were found in patients with old age and underlying diseases at admission and were characteristic for the development of severe COVID-19. Severe COVID-19 developed preferentially in patients with underlying compromised immunity and was not associated with initial virus levels. Higher SARS-CoV-2 RNA levels in severe cases were apparently a result of impaired immune control associated with dysregulation of inflammation.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , RNA Viral/análise , Linfócitos T/imunologia , Adulto , Idoso , Betacoronavirus/imunologia , Biomarcadores/sangue , China/epidemiologia , Estudos de Coortes , Infecções por Coronavirus/sangue , Feminino , Humanos , Mediadores da Inflamação/sangue , Contagem de Linfócitos , Subpopulações de Linfócitos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/sangue , Prognóstico , RNA Viral/genética , Estudos Retrospectivos , Carga Viral
11.
PLoS Pathog ; 16(6): e1008568, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32516328

RESUMO

Human herpesvirus 6 (HHV-6) is an important immunosuppressive and immunomodulatory virus worldwide. However, whether and how HHV-6 infection influences the metabolic machinery of the host cell to provide the energy and biosynthetic resources for virus propagation remains unknown. In this study, we identified that HHV-6A infection promotes glucose metabolism in infected T cells, resulting in elevated glycolytic activity with an increase of glucose uptake, glucose consumption and lactate secretion. Furthermore, we explored the mechanisms involved in HHV-6A-mediated glycolytic activation in the infected T cells. We found increased expressions of the key glucose transporters and glycolytic enzymes in HHV-6A-infected T cells. In addition, HHV-6A infection dramatically activated AKT-mTORC1 signaling in the infected T cells and pharmacological inhibition of mTORC1 blocked HHV-6A-mediated glycolytic activation. We also found that direct inhibition of glycolysis by 2-Deoxy-D-glucose (2-DG) or inhibition of mTORC1 activity in HHV-6A-infected T cells effectively reduced HHV-6 DNA replication, protein synthesis and virion production. These results not only reveal the mechanism of how HHV-6 infection affects host cell metabolism, but also suggest that targeting the metabolic pathway could be a new avenue for HHV-6 therapy.


Assuntos
Glicólise , Herpesvirus Humano 6/metabolismo , Infecções por Roseolovirus/metabolismo , Transdução de Sinais , Linfócitos T/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Linhagem Celular , Replicação do DNA/efeitos dos fármacos , DNA Viral/biossíntese , Desoxiglucose/farmacologia , Glucose/metabolismo , Humanos , Ácido Láctico/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Infecções por Roseolovirus/tratamento farmacológico , Infecções por Roseolovirus/patologia , Linfócitos T/patologia , Linfócitos T/virologia , Proteínas Virais/biossíntese , Vírion/metabolismo
13.
Neuropsychopharmacology ; 45(8): 1369-1379, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32353861

RESUMO

Schizophrenia (SCZ), bipolar disorder (BD), and major depressive disorder (MDD) are heritable psychiatric disorders with partially overlapping genetic liability. Shared and disorder-specific neurobiological abnormalities associated with familial risk for developing mental illnesses are largely unknown. We performed a meta-analysis of structural brain imaging studies in relatives of patients with SCZ, BD, and MDD to identify overlapping and discrete brain structural correlates of familial risk for mental disorders. Search for voxel-based morphometry studies in relatives of patients with SCZ, BD, and MDD in PubMed and Embase identified 33 studies with 2292 relatives and 2052 healthy controls (HC). Seed-based d Mapping software was used to investigate global differences in gray matter volumes between relatives as a group versus HC, and between those of each psychiatric disorder and HC. As a group, relatives exhibited gray matter abnormalities in left supramarginal gyrus, right striatum, right inferior frontal gyrus, left thalamus, bilateral insula, right cerebellum, and right superior frontal gyrus, compared with HC. Decreased right cerebellar gray matter was the only abnormality common to relatives of all three conditions. Subgroup analyses showed disorder-specific gray matter abnormalities in left thalamus and bilateral insula associated with risk for SCZ, in left supramarginal gyrus and right frontal regions with risk for BD, and in right striatum with risk for MDD. While decreased gray matter in right cerebellum might be a common brain structural abnormality associated with shared risk for SCZ, BD, and MDD, regional gray matter abnormalities in neocortex, thalamus, and striatum appear to be disorder-specific.

14.
Chemosphere ; 255: 126962, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32402887

RESUMO

The degradation of N,N-diethyl-meta-toluamide (DEET) in aqueous solution by the UV/monochloramine (UV/NH2Cl) process was examined systematically in this study. DEET was resistant to UV photolysis and chloramination, while the synchronous combination of UV irradiation and NH2Cl can effectively eliminate DEET, which was caused by the generation of hydroxyl radicals and reactive chlorine species. The former played the critical role in DEET degradation, while the contribution of the latter can be ignored. Under all investigated experimental conditions, DEET degradation in the UV/NH2Cl process followed the pseudo-first-order kinetic model. The water quality parameters exerted the complicated impact. Reducing solution pH and raising water temperature both favored the DEET removal. The presence of sulfate, humic acid and fulvic acid accelerated the degradation, while the introduction of bicarbonate and high-concentration chloride retarded the removal. The plausible degradation pathways of DEET in the UV/NH2Cl process were proposed through the combination of QTOF/MS analysis and DFT calculation, and mainly involved in the cleavage of C-N bond, dealkylation, mono- and polyhydroxylation. The acute toxicity of reacted solution underwent a trend of first increasing and then decreasing with the prolonged irradiation time, which can be well illustrated by quantitative structure-activity relationship analysis. Electrical energy per order was employed to determine the energy consumption and the optimal conditions were determined as UV fluence of 369.9-493.2 mJ cm-2 and NH2Cl dosage of 5-20 mg L-1.


Assuntos
DEET/química , Poluentes Químicos da Água/química , Purificação da Água/métodos , Cloraminas , Cloretos , Cloro , Radical Hidroxila , Cinética , Oxirredução , Fotólise , Raios Ultravioleta , Água
15.
Parkinsons Dis ; 2020: 5190703, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32399170

RESUMO

Freezing of gait (FOG) is a disabling phenomenon that is described by patients with Parkinson's disease (PD). Not only gait may be involved in the freezing phenomenon, but also some nonmotor symptoms, such as freezing of urination (FOU) in this case. The characters of urinary dysfunctions in this case resemble "off" freezing: (1) abrupt difficulty in starting or continuing in urination; (2) the urinary dysfunctions fluctuated with medication state; and (3) the urinary dysfunctions could be alleviated dramatically by an external cueing. Urinary dysfunctions in this patient (and maybe more PD patients) are associated not only with the classical "nonmotor symptoms" but also the freezing phenomenon. FOU could be a part of the spectrum of freezing symptoms. The subtypes of the freezing phenomenon will shed light on the PD pathophysiology and clinical treatment.

16.
J Virol ; 94(13)2020 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-32295911

RESUMO

Human herpesviruses 6A and 6B (HHV-6A and HHV-6B, respectively) are two virus species in the betaherpesvirus subfamily that exhibit T cell tropism. CD46 and CD134 are the cellular receptors for HHV-6A and HHV-6B, respectively. Interestingly, the efficiency of HHV-6A/6B entry is different among different types of target cells despite similar receptor expression levels on these cells. Here, we found that the cellular factor gp96 (also known as glucose-regulated protein 94 [GRP94]) is expressed on the cell surface and interacts with viral glycoprotein Q1 (gQ1) during virus entry. gp96 cell surface expression levels are associated with the efficiency of HHV-6A and HHV-6B entry into target cells. Both loss-of-function and gain-of-function experiments indicated that gp96 plays an important role in HHV-6 infection. Our findings provide new insight into the HHV-6 entry process and might suggest novel therapeutic targets for HHV-6 infection.IMPORTANCE Although new clinical importance has been revealed for human herpesviruses 6A (HHV-6A) and 6B, much is still unknown about the life cycles of these viruses in target cells. We identified a novel cellular factor, gp96, that is critical for both HHV-6A and -6B entry into host cells. As gp96 can function as an adjuvant in vaccine development for both infectious agents and cancers, it can be a potential therapeutic target for infection by these two viruses.

17.
Cell Death Dis ; 11(3): 207, 2020 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-32231200

RESUMO

This study aimed to evaluate treatment response, survival, safety profiles, and predictive factors to chimeric antigen receptor T cell (CAR-T) therapy in Chinese patients with relapsed or refractory B cell acute lymphoblast leukemia (R/R B-ALL). 39R/R B-ALL patients who underwent CAR-T therapy were included. Baseline data were collected from patients' electronic medical records. Patients' peripheral bloods, bone marrow aspirates, and biopsies were obtained for routine examination, and treatment response and survival profiles as well as adverse events were evaluated. The rates of complete remission (CR), CR with minimal residual disease (MRD) negative/positive, and bridging to hematopoietic stem-cell transplantation (HSCT) were 92.3%, 76.9%, 15.4%, and 43.6%, respectively. The median event-free survival (EFS) was 11.6 months (95% confidence interval (CI): 4.0-19.2 months) and median overall survival (OS) was 14.0 months (95% CI: 10.9-17.1 months). Bridging to HSCT independently predicted better EFS and OS, while high bone marrow blasts level independently predicted worse EFS. The incidence of cytokine release syndrome (CRS) was 97.4%, and refractory disease as well as decreased white blood cell independently predicted higher risk of severe CRS. Other common adverse events included hematologic toxicities (grade I: 5.1%, grade II: 7.7%, grade III: 17.9%, grade IV: 69.2%), neurotoxicity (28.2%), infection (38.5%), and admission for intensive care unit (10.3%). In conclusion, CAR-T therapy presents with promising treatment response, survival and safety profiles, and higher disease burden predicts worse survival as well as increased risk of severe CRS in Chinese R/R B-ALL patients.

18.
J Med Virol ; 92(6): 667-674, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32167180

RESUMO

Starting around December 2019, an epidemic of pneumonia, which was named COVID-19 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full-length genomic sequences of SARAS-CoV-2 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS-CoV-2 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%-100%) at the nucleotide level and 99.99% (99.79%-100%) at the amino acid level. Although overall variation in open-reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS-COV-2, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS-CoV-2 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS-CoV-2 infection in the future.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Genoma Viral , Taxa de Mutação , Pandemias , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Sequência de Bases , Betacoronavirus/classificação , Betacoronavirus/isolamento & purificação , Betacoronavirus/patogenicidade , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Bases de Dados Genéticas , Humanos , Fases de Leitura Aberta , Filogenia , Pneumonia Viral/transmissão , Pneumonia Viral/virologia , RNA Viral/genética , Padrões de Referência , Alinhamento de Sequência , Homologia de Sequência do Ácido Nucleico
19.
Microbiologyopen ; 9(1): e00955, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31782623

RESUMO

Lake anchovy (Coilia ectenes taihuensis) is a sedentary, dominant fish species that forms an unmanaged fishery in Taihu Lake, eastern China. The environment and developmental stage of lake anchovy are likely important drivers of their gut microbiome, which is linked to host health and development. To investigate the relationship between the gut microbiome and three defined factors (fish sex, fish body size, and the local habitat), high-throughput sequencing of the 16S ribosomal RNA gene was used to study the microorganisms of 184 fish samples and four water samples collected in Taihu Lake. Four dominant bacterial phyla (Proteobacteria, Firmicutes, Planctomycetes, and Cyanobacteria) were present in all fish samples. We compared the microbial communities of males and females and found that the relative abundance of Corynebacteriaceae was significantly higher in males than in females, while the opposite trend was detected for Sphingomonadaceae. We also discovered that the relative abundance of Firmicutes was positively correlated with fish body size and that the proportions of Proteobacteria and Tenericutes were lower in larger fish than in fish of other sizes. Finally, we found that the difference in microbial richness between eastern and northern Taihu Lake was the most marked. Lake anchovy was rich in Lactobacillus and Clostridium in the eastern site, while those in the northern site had the highest abundance of Sphingomonas and Methylobacterium, suggesting that the local habitat may also influence the intestinal microbiome. These findings will not only help researchers understand the community composition of the intestinal microflora of lake anchovy but also contribute to the protection of fish resources in Lake Taihu and the sustainable use of lake anchovy.

20.
Neurotox Res ; 37(1): 67-76, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31691188

RESUMO

Cognitive deficits and psychiatric disorders have been regarded as the most common clinical symptoms of methamphetamine (MA) users. Accumulating evidence has shown that liver disease may be involved in cognitive deficits and psychiatric disorders. This study examines whether cognitive deficits and psychiatric symptoms are associated with serum levels of liver biomarkers in MA users. Cognition was assessed by the Repeatable Battery for the Assessment of neuropsychological Status (RBANS). Psychiatric symptoms were assessed by the Symptom Checklist-90 (SCL-90). Liver function was assessed by serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), total protein, albumin, globulin, Apolipoprotein B (ApoB), triglyceride, total cholesterol, and glucose concentrations in 106 MA addicts and 76 controls. Compared to control subjects, MA users had greater severity of psychotic symptoms on the dimension of somatization, depression, anxiety, psychoticism, addiction, and global severity index in SCL-90, and lower scores of cognition, including the total RBANS score and all five subscales. The globulin levels were increased, while the albumin, albumin/globulin, and ApoB levels were decreased. ApoB levels were positively correlated with immediate memory, attention, and total RBANS score. Furthermore, stepwise multivariate regression analysis indicated that ApoB levels were associated with immediate memory, attention, and total RBANS score. The findings of this study suggest that MA addicts might experience cognitive deficits, psychiatric disorders, and liver damage. Serum ApoB levels may be involved in cognitive deficits; thus, improving liver function may help to treat cognitive deficits and psychiatric disorders in MA addicts.

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