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1.
Artigo em Inglês | MEDLINE | ID: mdl-38639759

RESUMO

During investigations of invertebrate-associated fungi in Yunnan Province of China, a new species, Sporodiniella sinensis sp. nov., was collected. Morphologically, S. sinensis is similar to Sporodiniella umbellata; however, it is distinguished from S. umbellata by its greater number of sporangiophore branches, longer sporangiophores, larger sporangiospores, and columellae. The novel species exhibits similarities of 91.62 % for internal transcribed spacer (ITS), 98.66-99.10 % for ribosomal small subunit (nrSSU), and 96.36-98.22 % for ribosomal large subunit (nrLSU) sequences, respectively, compared to S. umbellata. Furthermore, phylogenetic analyses based on combined sequences of ITS, nrLSU and nrSSU show that it forms a separate clade in Sporodiniella, and clusters closely with S. umbellata with high statistical support. The phylogenetic and morphological evidence support S. sinensis as a distinct species. Here, it is formally described and illustrated, and compared with other relatives.


Assuntos
Ácidos Graxos , Mucorales , Animais , Filogenia , China , Análise de Sequência de DNA , Composição de Bases , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Técnicas de Tipagem Bacteriana , Ácidos Graxos/química , Invertebrados
2.
Int Wound J ; 21(2): e14756, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38339818

RESUMO

The primary objective of this meta-analysis was to provide the comprehensive understanding of the intricate correlation that existed between immune senescence and its effects on the advancement of lung cancer as well as recovery of cutaneous wounds. By conducting this systematic review of six rigorous studies utilizing databases such as PubMed and Web of Science, this research examined the multitude of facets pertaining to immune aging and consequences it bear on the health outcomes. The incorporated studies encompassed wide range of geographical and methodological viewpoints, with the specific emphasis on non-small-cell lung cancer and diverse scenarios related to wound recovery. This analysis synthesized discoveries regarding therapeutic responses, cellular and molecular mechanisms and impact of lifestyle factors on immune senescence. The findings suggested that immune senescence has substantial impact on the effectiveness of treatments for lung cancer and cutaneous wounds healing process; therefore, targeted therapies and holistic approaches may be able to mitigate these effects. By following the revised PRISMA guidelines, this meta-analysis guarantee thorough and ethically sound methodology for amalgamating pre-existing literature. The study concluded by emphasizing the critical nature of comprehending immune senescence in the context of clinical practice and proposed avenues for further investigation to enhance health results among the elderly.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Idoso , Neoplasias Pulmonares/terapia , Carcinoma Pulmonar de Células não Pequenas/terapia , Cicatrização , Envelhecimento
3.
Mol Psychiatry ; 27(11): 4611-4623, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36198764

RESUMO

Alcohol withdrawal is a clinically important consequence and potential driver of Alcohol Use Disorder. However, susceptibility to withdrawal symptoms, ranging from craving and anxiety to seizures and delirium, varies greatly. Selectively bred Withdrawal Seizure-Prone (WSP) and Seizure-Resistant (WSR) mice are an animal model of differential susceptibility to withdrawal and phenotypes with which withdrawal severity correlates. To identify innate drivers of alcohol withdrawal severity, we performed a multi-omic study of the WSP and WSR lines and F2 mice derived from them, using genomic, genetic, and transcriptomic analyses. Genes implicated in seizures and epilepsy were over-represented among those that segregated between WSP and WSR mice and that displayed differential expression in F2 mice high and low in withdrawal. Quantitative trait locus (QTL) analysis of ethanol withdrawal convulsions identified several genome-wide significant loci and pointed to genes that modulate potassium channel function and neural excitability. Perturbations of expression of genes involved in synaptic transmission, including GABAergic and glutamatergic genes, were prominent in prefrontal cortex transcriptome. Expression QTL (eQTL) analysis fine mapped genes within the peak ethanol withdrawal QTL regions. Genetic association analysis in human subjects provided converging evidence for the involvement of those genes in severity of alcohol withdrawal and dependence. Our results reveal a polygenic network and neural signaling pathways contributing to ethanol withdrawal seizures and related phenotypes that overlap with genes modulating epilepsy and neuronal excitability.


Assuntos
Alcoolismo , Epilepsia , Síndrome de Abstinência a Substâncias , Camundongos , Humanos , Animais , Síndrome de Abstinência a Substâncias/genética , Alcoolismo/genética , Convulsões/genética , Etanol
4.
Int J Mol Sci ; 24(8)2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37108681

RESUMO

Methylotrophic bacteria are widely distributed in nature and can be applied in bioconversion because of their ability to use one-carbon source. The aim of this study was to investigate the mechanism underlying utilization of high methanol content and other carbon sources by Methylorubrum rhodesianum strain MB200 via comparative genomics and analysis of carbon metabolism pathway. The genomic analysis revealed that the strain MB200 had a genome size of 5.7 Mb and two plasmids. Its genome was presented and compared with that of the 25 fully sequenced strains of Methylobacterium genus. Comparative genomics revealed that the Methylorubrum strains had closer collinearity, more shared orthogroups, and more conservative MDH cluster. The transcriptome analysis of the strain MB200 in the presence of various carbon sources revealed that a battery of genes was involved in the methanol metabolism. These genes are involved in the following functions: carbon fixation, electron transfer chain, ATP energy release, and resistance to oxidation. Particularly, the central carbon metabolism pathway of the strain MB200 was reconstructed to reflect the possible reality of the carbon metabolism, including ethanol metabolism. Partial propionate metabolism involved in ethyl malonyl-CoA (EMC) pathway might help to relieve the restriction of the serine cycle. In addition, the glycine cleavage system (GCS) was observed to participate in the central carbon metabolism pathway. The study revealed the coordination of several metabolic pathways, where various carbon sources could induce associated metabolic pathways. To the best of our knowledge, this is the first study providing a more comprehensive understanding of the central carbon metabolism in Methylorubrum. This study provided a reference for potential synthetic and industrial applications of this genus and its use as chassis cells.


Assuntos
Metanol , Methylobacterium , Metanol/metabolismo , Biocombustíveis , Carbono/metabolismo , Methylobacterium/metabolismo , Genômica
5.
J Environ Manage ; 345: 118707, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37536132

RESUMO

Composting is a common and effective strategy for reducing antibiotic resistance genes (ARGs) and antibiotic-resistant bacteria (ARB) from animal manure. However, it is unclear whether the advantages of composting for the control of ARGs and ARB can be further increased in land application. This study investigated the fate of ARB and ARGs after land application of swine-manure composts (SMCs) to three different soil types (red soil, loess and black soil). The results showed that although the SMCs caused an increase in the abundance of total ARGs in the soil in the short period, they significantly reduced (p < 0.01) the abundance of total ARGs after 82 days compared to the control. The decay rate of ARGs reflected by the half-life times (t1/2) varied by soil type, with red soil being the longest. The SMCs mainly introduced ermF, tetG and tetX into the soils, while these ARGs quickly declined to the control level. Notably, SMCs increased the number of ARB in the soils, especially for cefotaxime-resistant bacteria. Although SMCs only affected the microbiome significantly during the early stage (p < 0.05), it took a much longer time for the microbiome to recover compared to the control. Statistical analysis indicated that changes in the microbial community contributed more to the fate of ARGs during SMCs land application than other factors. Overall, it is proposed that the advantages of ARGs control in the composting process for swine manure can be further increased in land application, but it can still bring some risks in regard to ARB.


Assuntos
Compostagem , Solo , Animais , Suínos , Genes Bacterianos , Esterco/análise , Antagonistas de Receptores de Angiotensina , Microbiologia do Solo , Inibidores da Enzima Conversora de Angiotensina , Bactérias/genética , Antibacterianos/farmacologia
6.
J Environ Manage ; 334: 117394, 2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-36774902

RESUMO

The global climate change made the heavy rainfall happen more frequently, and the non-point source pollution caused by it would exacerbate the risk to the water ecological environment. In this study, we took a reservoir (Shahe reservoir, Beijing, China) supplied with reclaimed water as an exapmle to investigate how spatiotemporal changes in the quantity and diversity of prokaryotic, eukaryotic, and algal communities respond to heavy rainfall. Results showed that heavy rainfall could directly impact the composition of the prokaryotic community by introducing amounts of runoff closely associated bacterium especially for the human potential pathogens such as Aliarcobacter, Aeromonas and Pseudomonas in the Shahe reservoir area. While the eukaryotic community was rather stable, and the development and changes in algal communities occurred in the last few days after heavy rainfall. The microbial source tracking through FEAST indicated that Nansha river (S) was the major contributor to the development of all the three concerned communities in the reservoir. The co-occurrence analysis showed that the modules with the highest cumulative abundance in each community were all strongly and positively connected with Chl-a, pH, turbidity, COD and TOC, but negatively correlated with NO3-N (p < 0.01). The network analysis showed that the eukaryotes played a key role in the interaction network among the three communities, and were more likely to interact with algae and prokaryotes. It was suggested that the controlling of human potential pathogens associated with prokaryotic community should be emphasized at the beginning of the heavy rainfall, but the prevention of the eutrophication bloom should be another focus after the heavy rainfall. This study provided valuable information concerning the role of heavy rainfall on the water ecological environment from the perspective of microbial community.


Assuntos
Eucariotos , Água , Humanos , Qualidade da Água , Eutrofização , Rios , China
7.
Addict Biol ; 27(2): e13144, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35229939

RESUMO

Iron loading has been consistently reported in those with alcohol use disorder (AUD), but its effect on the clinical course of the disease is not yet fully understood. Here, we conducted a cohort study to examine whether peripheral iron measures, genetic variation in HFE rs1799945 and their interaction differed between 594 inpatient participants with alcohol use disorder (AUD) undergoing detoxification and 472 healthy controls (HC). We also assessed whether HFE rs1799945 was associated with elevated peripheral iron and can serve as a predictor of withdrawal severity. AUD patients showed significantly higher serum transferrin saturation than HC. Within the AUD group, transferrin saturation significantly predicted withdrawal symptoms (CIWA-Ar) and cumulative dose of benzodiazepine treatment during the first week of detoxification, which is an indicator of withdrawal severity. HFE rs1799945 minor allele carriers showed elevated transferrin saturation compared to non-carriers, both in AUD and healthy controls. Exploratory analyses indicated that, within the AUD cohort, HFE rs1799945 predicted CIWA withdrawal scores, and this relationship was significantly mediated by transferrin saturation. We provide evidence that serum transferrin saturation predicts alcohol withdrawal severity in AUD. Moreover, our findings replicated previous studies on elevated serum transferrin saturation in AUD and an involvement of HFE rs1799945 in serum transferrin saturation levels in both AUD and healthy controls. Future studies may use transferrin saturation measures as predictors for treatment or potentially treat iron overload to ameliorate withdrawal symptoms.


Assuntos
Alcoolismo , Sobrecarga de Ferro , Síndrome de Abstinência a Substâncias , Alcoolismo/genética , Estudos de Coortes , Genótipo , Proteína da Hemocromatose/genética , Humanos , Sobrecarga de Ferro/genética , Síndrome de Abstinência a Substâncias/genética , Transferrina/análise , Transferrina/genética
8.
Proc Natl Acad Sci U S A ; 116(26): 13107-13115, 2019 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-31182603

RESUMO

Artificially selected model organisms can reveal hidden features of the genetic architecture of the complex disorders that they model. Addictions are disease phenotypes caused by different intermediate phenotypes and pathways and thereby are potentially highly polygenic. High responder (bHR) and low responder (bLR) rat lines have been selectively bred (b) for exploratory locomotion (EL), a behavioral phenotype correlated with novelty-seeking, impulsive response to reward, and vulnerability to addiction, and is inversely correlated with spontaneous anxiety and depression-like behaviors. The rapid response to selection indicates loci of large effect for EL. Using exome sequencing of HR and LR rats, we identified alleles in gene-coding regions that segregate between the two lines. Quantitative trait locus (QTL) analysis in F2 rats derived from a bHR × bLR intercross confirmed that these regions harbored genes affecting EL. The combined effects of the seven genome-wide significant QTLs accounted for approximately one-third of the total variance in EL, and two-thirds of the variance attributable to genetic factors, consistent with an oligogenic architecture of EL estimated both from the phenotypic distribution of F2 animals and rapid response to selection. Genetic association in humans linked APBA2, the ortholog of the gene at the center of the strongest QTL, with substance use disorders and related behavioral phenotypes. Our finding is also convergent with molecular and animal behavioral studies implicating Apba2 in locomotion. These results provide multilevel evidence for genes/loci influencing EL. They shed light on the genetic architecture of oligogenicity in animals artificially selected for a phenotype modeling a more complex disorder in humans.


Assuntos
Comportamento Aditivo/genética , Caderinas/genética , Comportamento Exploratório/fisiologia , Locomoção/genética , Proteínas do Tecido Nervoso/genética , Transtornos Relacionados ao Uso de Substâncias/genética , Animais , Comportamento Aditivo/fisiopatologia , Comportamento Animal/fisiologia , Proteínas de Transporte/genética , Estudos de Casos e Controles , Modelos Animais de Doenças , Feminino , Finlândia , Predisposição Genética para Doença , Técnicas de Genotipagem , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Ratos , Recompensa , Sequenciamento do Exoma
9.
Water Sci Technol ; 85(10): 3023-3035, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35638803

RESUMO

Anaerobic activated sludge plays a key role in the anaerobic digestion (AD) treatment of wastewater. The ability of anaerobic activated sludge to endure stress shock determines the performance of AD. In this study, the resistance of anaerobic activated sludge acclimated by three feeding patterns (continuous, semi-continuous, and pulse) to four stress shocks, including low pH influent, high OLR (organic loading rate), high ammonium and high sulfate, was investigated respectively. The results showed that the anaerobic activated sludge acclimated by semi-continuous feeding had the best resistance to high OLR shock, followed by pulse feeding, and then continuous feeding. There was no significant difference in the resistance of the three activated sludge to the other stress shocks. Under stress shock, the microbial community structure and abundance of specific functional microorganisms in the activated sludge acclimated by different feeding patterns varied, while the relative abundance of Methanosarcinaceae in the anaerobic activated sludge increased. The variation in the relative abundance of specific functional microorganisms was in charge of the differences in the resistance of anaerobic activated sludge. Overall, the results presented herein provide reference for improving the stability and effectiveness of activated sludge under adverse conditions.


Assuntos
Microbiota , Esgotos , Anaerobiose , Comportamento Alimentar , Águas Residuárias
10.
J Gastroenterol Hepatol ; 35(10): 1668-1675, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32250469

RESUMO

BACKGROUND AND AIM: The role of STMN1 in the development and progression of esophageal carcinoma is not yet determined. The present study aimed to systematically evaluate the correlation between STMN1 and prognosis of patients with esophageal carcinoma. METHODS: Electronic databases including PubMed, Embase, the Cochrane library, and Chinese Biomedical Literature Database (CBM) were searched to identify studies evaluating the impact of STMN1 on the survival of esophageal cancer patients, without the language limitation. Two investigators screened the literature according to the inclusion and exclusion criteria and evaluated the quality of the included studies. The combined analysis was performed using RevMan 5.3 software. RESULTS: A total of eight studies, involving 1240 esophageal carcinoma patients, were included in this retrospective design. Meta-analysis showed that esophageal carcinoma patients with low STMN1 had a superior overall survival and disease-free survival than those with high expression of STMN1. Compared with the high expression of STMN1, the 5-year survival rate was significantly higher in patients with low level of STMN1. Patients with high STMN1 expression had a higher risk of experiencing clinical grade III-IV disease, lymph node metastasis, and tumor invasion than those with low STMN1. CONCLUSION: STMN1 is an indicator for the prognosis of esophageal carcinoma patients.


Assuntos
Carcinoma/genética , Neoplasias Esofágicas/genética , Regulação da Expressão Gênica , Expressão Gênica , Estudos de Associação Genética , Estatmina/genética , Estatmina/metabolismo , Povo Asiático , Carcinoma/mortalidade , Carcinoma/patologia , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
11.
Biotechnol Lett ; 41(1): 69-77, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30361889

RESUMO

OBJECTIVE: To identify potential target genes involved in L-serine biosynthesis in Methylobacterium sp. MB200 and to evaluate the gnd genetically-engineered strains for L-serine production. RESULTS: Five genes that are not associated with the central metabolic pathway but with L-serine biosynthesis were identified from Methylobacterium sp. MB200 mutants. Gene gnd, encoding 6-phosphogluconate dehydrogenase (PGDH), was selected for further evaluation. The gnd deletion mutant showed a 600% increase in D-serine tolerance and an 80% decrease in PGDH activity compared to Methylobacterium sp. MB200. gnd over-expression did not affect D-serine tolerance, whereas it did increase enzyme-activity up to 136%. Additionally, analysis revealed that in Methylobacterium sp. MB200, L-serine inhibited PGDH activity. The deletion of gnd did not affect growth, whereas it did enhance the biosynthesis of L-serine, resulting in a 225% increase in production of L-serine compared to the wild-type. CONCLUSION: gnd, one of the five genes identified here that is associated with L-serine synthesis, can be developed as a potential candidate for metabolic engineering to promote L-serine synthesis in Methylobacterium sp. MB200.


Assuntos
Proteínas de Bactérias/genética , Deleção de Genes , Methylobacterium/metabolismo , Microrganismos Geneticamente Modificados/metabolismo , Fosfogluconato Desidrogenase/genética , Serina/biossíntese , Methylobacterium/genética , Microrganismos Geneticamente Modificados/genética , Serina/genética
12.
Cell Physiol Biochem ; 44(4): 1425-1434, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29186712

RESUMO

BACKGROUND/AIMS: In contrast to men, women have experienced a rapid increase in lung cancer mortality. Numerous studies have found that the sex differences in lung cancer are due to reproductive hormones. Experiments in female mice with and without ovariectomy were performed to explore the possible mechanism by which sex hormones (and their receptors) influence lung cancer. METHODS: Twenty-four female C57BL/6 mice aged 56-62 days were randomly divided into the ovariectomized group and the control group. In the ovariectomized group, the bilateral ovaries were removed via the dorsal approach, while the control group underwent a sham operation with bilateral ovarian fat resection at the same sites. After 3 weeks of recovery, Lewis lung cancer cells were transplanted into these mice by subcutaneous inoculation of a tumour cell suspension to establish the ovariectomized lung cancer model. Beginning on the 6th day after subcutaneous inoculation, mouse weight and transplanted tumour volume were measured every 3 days. After 3 weeks, all the mice were killed by cervical dislocation, and we measured the tumour weight. Mouse serum and tumour tissues were removed. Then, the serum levels of E2 (oestradiol) and T (testosterone) were detected by ELISA; the protein expression levels of AR (androgen receptor), ERα (oestrogen receptor α) and ERß (oestrogen receptor ß) were detected by Western Blot and IHC (immunohistochemistry); and the mRNA expression levels of AR, ERα and ERß were detected by qRT-PCR (quantitative real-time polymerase chain reaction) in the ovariectomized and control groups. RESULTS: Compared with the control group, both mouse weight and transplanted tumour volume increased rapidly in the ovariectomized group, and the transplanted tumour weight was significantly heavier in the ovariectomized group (1.83±0.40 and 3.13±0.43, P<0.05). E2 and T serum levels decreased exponentially in the ovariectomized group, while the E2/T ratio increased compared with the control group (E2: 55.88±11.45 and 78.21±9.37; T: 0.82±0.14 and 1.46±0.16; ratio: 69.62±14.43±29.81 and 52.22±5.42; all P<0.05). The Western blot and IHC results indicated that AR, ERα and ERß protein expression levels were obviously higher in transplanted tumour and lung tissues from the ovariectomized group, with particular increases in ERß in transplanted tumour tissue and in ERα in lung tissue. The PCR results also showed markedly higher mRNA expression levels of AR, ERα and ERß in the ovariectomized group, and in particular, ERß in transplanted tumour tissue and ERα in lung tissue were significantly increased in the ovariectomized group. CONCLUSION: Ovariectomy decreased E2 and T serum levels and increased the E2/T ratio in mice, and this imbalance in the internal environment promoted the growth of transplanted tumours. Sex hormone disorder not only promoted transplanted tumour growth but also significantly reduced the protein and mRNA expression levels of sex hormone receptors. The metabolism of E2 and T may affect the growth, proliferation and metabolism of lung cancer cells, and the mechanism by which sex hormones and their receptors influence lung cancer is worthy of further research.


Assuntos
Estradiol/sangue , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Neoplasias Pulmonares/patologia , Receptores Androgênicos/metabolismo , Testosterona/sangue , Animais , Peso Corporal , Linhagem Celular Tumoral , Ensaio de Imunoadsorção Enzimática , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Feminino , Humanos , Imuno-Histoquímica , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/mortalidade , Camundongos , Camundongos Endogâmicos C57BL , Ovariectomia , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores Androgênicos/genética , Transplante Heterólogo
13.
Artigo em Inglês | MEDLINE | ID: mdl-27207918

RESUMO

BACKGROUND: Reduction in brain volume, especially gray matter volume, has been shown to be one of the many deleterious effects of prolonged alcohol consumption. High variance in the degree of gray matter tissue shrinkage among alcohol-dependent individuals and a previous neuroimaging genetics report suggest the involvement of environmental and/or genetic factors, such as superoxide dismutase 2 (SOD2). Identification of such underlying factors will help in the clinical management of alcohol dependence. METHODS: We analyzed quantitative magnetic resonance imaging and genotype data from 103 alcohol users, including both light drinkers and treatment-seeking alcohol-dependent individuals. Genotyping was performed using a custom gene array that included genes selected from 8 pathways relevant to chronic alcohol-related brain volume loss. RESULTS: We replicated a significant association of a functional SOD2 single nucleotide polymorphism with normalized gray matter volume, which had been reported previously in an independent smaller sample of alcohol-dependent individuals. The SOD2-related genetic protection was observed only at the cohort's lower drinking range. Additional associations between normalized gray matter volume and other candidate genes such as alcohol dehydrogenase gene cluster (ADH), GCLC, NOS3, and SYT1 were observed across the entire sample but did not survive corrections for multiple comparisons. CONCLUSION: Converging independent evidence for a SOD2 gene association with gray matter volume shrinkage in chronic alcohol users suggests that SOD2 genetic variants predict differential brain volume loss mediated by free radicals. This study also provides the first catalog of genetic variations relevant to gray matter loss in chronic alcohol users. The identified gene-brain structure relationships are functionally pertinent and merit replication.

14.
Behav Genet ; 46(2): 151-69, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26392368

RESUMO

The mu1 opioid receptor gene, OPRM1, has long been a high-priority candidate for human genetic studies of addiction. Because of its potential functional significance, the non-synonymous variant rs1799971 (A118G, Asn40Asp) in OPRM1 has been extensively studied, yet its role in addiction has remained unclear, with conflicting association findings. To resolve the question of what effect, if any, rs1799971 has on substance dependence risk, we conducted collaborative meta-analyses of 25 datasets with over 28,000 European-ancestry subjects. We investigated non-specific risk for "general" substance dependence, comparing cases dependent on any substance to controls who were non-dependent on all assessed substances. We also examined five specific substance dependence diagnoses: DSM-IV alcohol, opioid, cannabis, and cocaine dependence, and nicotine dependence defined by the proxy of heavy/light smoking (cigarettes-per-day >20 vs. ≤ 10). The G allele showed a modest protective effect on general substance dependence (OR = 0.90, 95% C.I. [0.83-0.97], p value = 0.0095, N = 16,908). We observed similar effects for each individual substance, although these were not statistically significant, likely because of reduced sample sizes. We conclude that rs1799971 contributes to mechanisms of addiction liability that are shared across different addictive substances. This project highlights the benefits of examining addictive behaviors collectively and the power of collaborative data sharing and meta-analyses.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Receptores Opioides mu/genética , Transtornos Relacionados ao Uso de Substâncias/genética , População Branca/genética , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Criança , Estudos de Coortes , Frequência do Gene/genética , Humanos , Masculino , Tamanho da Amostra
15.
Alcohol Clin Exp Res ; 40(1): 93-101, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26727527

RESUMO

BACKGROUND: Animal and human studies indicate that GABBR1, encoding the GABAB1 receptor subunit, and SLC6A1, encoding the neuronal gamma-aminobutyric acid (GABA) transporter GAT1, play a role in addiction by modulating synaptic GABA. Therefore, variants in these genes might predict risk/resilience for alcoholism. METHODS: This study included 3 populations that differed by ethnicity and alcoholism phenotype: African American (AA) men: 401 treatment-seeking inpatients with single/comorbid diagnoses of alcohol and drug dependence, 193 controls; Finnish Caucasian men: 159 incarcerated alcoholics, half with comorbid antisocial personality disorder, 181 controls; and a community sample of Plains Indian (PI) men and women: 239 alcoholics, 178 controls. Seven GABBR1 tag single nucleotide polymorphisms were genotyped in the AA and Finnish samples; rs29220 was genotyped in the PI for replication. Also, a uniquely African, functional SLC6A1 insertion promoter polymorphism (IND) was genotyped in the AAs. RESULTS: We found a significant and congruent association between GABBR1 rs29220 and alcoholism in all 3 populations. The major genotype (heterozygotes in AAs, Finns) and the major allele in PIs were significantly more common in alcoholics. Moreover, SLC6A1 IND was more abundant in controls, that is, the major genotype predicted alcoholism. An analysis of combined GABBR1 rs29220 and SLC6A1 IND genotypes showed that rs29220 heterozygotes, irrespective of their IND status, had an increased risk for alcoholism, whereas carriers of the IND allele and either rs29220 homozygote were more resilient. CONCLUSIONS: Our results show that with both GABBR1 and SLC6A1, the minor genotypes/alleles were protective against risk for alcoholism. Finally, GABBR1 rs29220 might predict treatment response/adverse effects for baclofen, a GABAB receptor agonist.


Assuntos
Alcoolismo/genética , Negro ou Afro-Americano/genética , Proteínas da Membrana Plasmática de Transporte de GABA/genética , Indígenas Norte-Americanos/genética , Receptores de GABA-B/genética , População Branca/genética , Adulto , Alelos , Estudos de Casos e Controles , Feminino , Finlândia , Predisposição Genética para Doença , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Fatores de Proteção , Quinolinas/metabolismo , Sulfonamidas/metabolismo , Transmissão Sináptica/genética
16.
Proc Natl Acad Sci U S A ; 110(42): 16963-8, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-24082084

RESUMO

Identification of genes influencing complex traits is hampered by genetic heterogeneity, the modest effect size of many alleles, and the likely involvement of rare and uncommon alleles. Etiologic complexity can be simplified in model organisms. By genomic sequencing, linkage analysis, and functional validation, we identified that genetic variation of Grm2, which encodes metabotropic glutamate receptor 2 (mGluR2), alters alcohol preference in animal models. Selectively bred alcohol-preferring (P) rats are homozygous for a Grm2 stop codon (Grm2 *407) that leads to largely uncompensated loss of mGluR2. mGluR2 receptor expression was absent, synaptic glutamate transmission was impaired, and expression of genes involved in synaptic function was altered. Grm2 *407 was linked to increased alcohol consumption and preference in F2 rats generated by intercrossing inbred P and nonpreferring rats. Pharmacologic blockade of mGluR2 escalated alcohol self-administration in Wistar rats, the parental strain of P and nonpreferring rats. The causal role of mGluR2 in altered alcohol preference was further supported by elevated alcohol consumption in Grm2 (-/-) mice. Together, these data point to mGluR2 as an origin of alcohol preference and a potential therapeutic target.


Assuntos
Consumo de Bebidas Alcoólicas/genética , Códon de Terminação , Receptores de Glutamato Metabotrópico , Transmissão Sináptica/genética , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Consumo de Bebidas Alcoólicas/metabolismo , Consumo de Bebidas Alcoólicas/patologia , Animais , Cruzamentos Genéticos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Ácido Glutâmico/metabolismo , Camundongos , Camundongos Knockout , Ratos , Ratos Wistar , Receptores de Glutamato Metabotrópico/antagonistas & inibidores , Receptores de Glutamato Metabotrópico/biossíntese , Receptores de Glutamato Metabotrópico/genética , Sinapses/genética , Sinapses/metabolismo , Transmissão Sináptica/efeitos dos fármacos
17.
Appl Microbiol Biotechnol ; 99(17): 7321-31, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25967653

RESUMO

Sludge bio-drying in which sludge is dried by means of the heat generated by the aerobic degradation of its own organic substances has been widely used for sludge treatment. A better understanding of the evolution of dissolved organic matter (DOM) and its degradation drivers during sludge bio-drying could facilitate its control. Aeration is one of the key factors that affect sludge bio-drying performance. In this study, two aeration strategies (pile I-the optimized and pile II-the current) were established to investigate their impacts on the evolution of DOM and the microbial community in a full-scale sludge bio-drying plant. A higher pile temperature in pile I caused pile I to enter the DOM and microbiology stable stage approximately2 days earlier than pile II. The degradation of easily degradable components in the DOM primarily occurred in the thermophilic phase; after that degradation, the DOM components changed a little. Along with the evolution of the DOM, its main degradation driver, the microbial community, changed considerably. Phyla Firmicutes and Proteobacteria were dominant in the thermophilic stage, and genus Ureibacillus, which was the primary thermophilic bacteria, was closely associated with the degradation of the DOM. In the mesophilic stage, the microbial community changed significantly at first and subsequently stabilized, and the genus Parapedobacter, which belongs to Bacteriodetes, became dominant. This study elucidates the interplay between the DOM and microbial community during sludge bio-drying.


Assuntos
Bactérias/classificação , Biota , Dessecação , Compostos Orgânicos/análise , Esgotos/química , Esgotos/microbiologia , Temperatura
18.
Antonie Van Leeuwenhoek ; 107(6): 1615-23, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25900453

RESUMO

A novel D-amino acid oxidase (DAAO) gene designated as daoE was cloned by the sequence-based screening of a plasmid metagenomic library of uncultured microorganisms from contaminated agricultural soil. The deduced amino acid sequence comparison and phylogenetic analysis indicated that daoE and other putative DAAOs are closely related. The putative DAAO gene was subcloned into a pETBlue-2 vector and overexpressed in Escherichia coli Tunner(DE3)pLacI. The recombinant protein was purified to homogeneity. The maximum activity of DaoE protein occurred at pH 8.0 and 37 °C. DaoE recombinant protein had an apparent K m of 2.96 mM, V max of 0.018 mM/min, k cat of 10.9/min, and k cat/K m of 1.16 × 10(4)/mol/min. The identification of this novel DAAO gene demonstrated the importance of metagenomic libraries in exploring new D-amino acid oxidases from environmental microorganisms to optimize their applications.


Assuntos
D-Aminoácido Oxidase/isolamento & purificação , D-Aminoácido Oxidase/metabolismo , Metagenoma , Microbiologia do Solo , Sequência de Aminoácidos , Clonagem Molecular , D-Aminoácido Oxidase/genética , Estabilidade Enzimática , Escherichia coli/genética , Escherichia coli/metabolismo , Biblioteca Gênica , Concentração de Íons de Hidrogênio , Cinética , Dados de Sequência Molecular , Filogenia , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Homologia de Sequência de Aminoácidos , Temperatura
19.
Curr Microbiol ; 71(1): 143-9, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26003628

RESUMO

Centenarians constitute a significant subpopulation in the Bama County of Guangxi province in China. The beneficial effects of intestinal microbiota, especially bifidobacteria of centenarians, have been widely accepted; however, knowledge about Bifidobacterium species in centenarians is not adequate. The aim of this study was to investigate the quantity and prevalence of fecal Bifidobacterium in healthy longevous individuals. Fecal samples from eight centenarians from Bama (aged 100 to 108 years), eight younger elderlies from Bama (aged 80 to 99 years), and eight younger elderlies from Nanning (aged 80 to 99 years) were analyzed using denaturing gradient gel electrophoresis, species-specific clone library, and quantitative polymerase chain reaction technology (qPCR). A total of eight different Bifidobacterium species were detected. B. dentium, B. longum, B. thermophilum, B. pseudocatenulatum/B. catenulatum, and B. adolescentis were common in fecal of centenarians and young elderly. B. minimum, B. saecularmay/B. pullorum/B. gallinarum, and B. mongoliense were found in centenarians but were absent in the younger elderlies. In addition, Bifidobacterium species found in centenarians were different from those found in Bama young elderly and Nanning young elderly, and the principal differences were the significant increase in the population of B. longum (P < 0.05) and B. dentium (P < 0.05) and the reduction in the frequency of B. adolescentis (P < 0.05), respectively. Centenarians tend to have more complex fecal Bifidobacterium species than young elderlies from different regions.


Assuntos
Carga Bacteriana , Bifidobacterium/classificação , Bifidobacterium/isolamento & purificação , Fezes/microbiologia , Idoso de 80 Anos ou mais , Bifidobacterium/genética , China , Eletroforese em Gel de Gradiente Desnaturante , Humanos , Reação em Cadeia da Polimerase em Tempo Real
20.
Nature ; 452(7190): 997-1001, 2008 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-18385673

RESUMO

Understanding inter-individual differences in stress response requires the explanation of genetic influences at multiple phenotypic levels, including complex behaviours and the metabolic responses of brain regions to emotional stimuli. Neuropeptide Y (NPY) is anxiolytic and its release is induced by stress. NPY is abundantly expressed in regions of the limbic system that are implicated in arousal and in the assignment of emotional valences to stimuli and memories. Here we show that haplotype-driven NPY expression predicts brain responses to emotional and stress challenges and also inversely correlates with trait anxiety. NPY haplotypes predicted levels of NPY messenger RNA in post-mortem brain and lymphoblasts, and levels of plasma NPY. Lower haplotype-driven NPY expression predicted higher emotion-induced activation of the amygdala, as well as diminished resiliency as assessed by pain/stress-induced activations of endogenous opioid neurotransmission in various brain regions. A single nucleotide polymorphism (SNP rs16147) located in the promoter region alters NPY expression in vitro and seems to account for more than half of the variation in expression in vivo. These convergent findings are consistent with the function of NPY as an anxiolytic peptide and help to explain inter-individual variation in resiliency to stress, a risk factor for many diseases.


Assuntos
Encéfalo/metabolismo , Emoções , Regulação da Expressão Gênica/genética , Variação Genética/genética , Neuropeptídeo Y/genética , Estresse Fisiológico/genética , Alelos , Ansiedade/genética , Transtornos de Ansiedade/genética , Encéfalo/fisiologia , Encéfalo/fisiopatologia , Expressão Facial , Finlândia/etnologia , Haplótipos/genética , Humanos , Linfócitos/metabolismo , Imageamento por Ressonância Magnética , Masculino , Neuropeptídeo Y/sangue , Peptídeos Opioides/metabolismo , Dor/genética , Polimorfismo de Nucleotídeo Único/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Estresse Fisiológico/psicologia , Estados Unidos/etnologia , População Branca/genética
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