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1.
Nature ; 562(7728): 583-588, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30356187

RESUMO

The development of the microbiome from infancy to childhood is dependent on a range of factors, with microbial-immune crosstalk during this time thought to be involved in the pathobiology of later life diseases1-9 such as persistent islet autoimmunity and type 1 diabetes10-12. However, to our knowledge, no studies have performed extensive characterization of the microbiome in early life in a large, multi-centre population. Here we analyse longitudinal stool samples from 903 children between 3 and 46 months of age by 16S rRNA gene sequencing (n = 12,005) and metagenomic sequencing (n = 10,867), as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We show that the developing gut microbiome undergoes three distinct phases of microbiome progression: a developmental phase (months 3-14), a transitional phase (months 15-30), and a stable phase (months 31-46). Receipt of breast milk, either exclusive or partial, was the most significant factor associated with the microbiome structure. Breastfeeding was associated with higher levels of Bifidobacterium species (B. breve and B. bifidum), and the cessation of breast milk resulted in faster maturation of the gut microbiome, as marked by the phylum Firmicutes. Birth mode was also significantly associated with the microbiome during the developmental phase, driven by higher levels of Bacteroides species (particularly B. fragilis) in infants delivered vaginally. Bacteroides was also associated with increased gut diversity and faster maturation, regardless of the birth mode. Environmental factors including geographical location and household exposures (such as siblings and furry pets) also represented important covariates. A nested case-control analysis revealed subtle associations between microbial taxonomy and the development of islet autoimmunity or type 1 diabetes. These data determine the structural and functional assembly of the microbiome in early life and provide a foundation for targeted mechanistic investigation into the consequences of microbial-immune crosstalk for long-term health.


Assuntos
Microbioma Gastrointestinal/imunologia , Microbioma Gastrointestinal/fisiologia , Inquéritos e Questionários , Adolescente , Animais , Bifidobacterium/classificação , Bifidobacterium/genética , Bifidobacterium/isolamento & purificação , Aleitamento Materno/estatística & dados numéricos , Estudos de Casos e Controles , Criança , Pré-Escolar , Análise por Conglomerados , Conjuntos de Dados como Assunto , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/microbiologia , Feminino , Firmicutes/classificação , Firmicutes/genética , Firmicutes/isolamento & purificação , Microbioma Gastrointestinal/genética , Humanos , Lactente , Masculino , Leite Humano/imunologia , Leite Humano/microbiologia , Animais de Estimação , RNA Ribossômico 16S/genética , Irmãos , Fatores de Tempo
2.
J Exp Bot ; 74(10): 3104-3121, 2023 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-36869735

RESUMO

Cysteine-rich receptor-like kinases (CRKs) are a large family of plasma membrane-bound receptors ubiquitous in higher plants. However, despite their prominence, their biological roles have remained largely elusive so far. In this study we report the characterization of an Arabidopsis mutant named crk10-A397T in which alanine 397 has been replaced by a threonine in the αC helix of the kinase domain of CRK10, known to be a crucial regulatory module in mammalian kinases. The crk10-A397T mutant is a dwarf that displays collapsed xylem vessels in the root and hypocotyl, whereas the vasculature of the inflorescence develops normally. In situ phosphorylation assays with His-tagged wild type and crk10-A397T versions of the CRK10 kinase domain revealed that both alleles are active kinases capable of autophosphorylation, with the newly introduced threonine acting as an additional phosphorylation site in crk10-A397T. Transcriptomic analysis of wild type and crk10-A397T mutant hypocotyls revealed that biotic and abiotic stress-responsive genes are constitutively up-regulated in the mutant, and a root-infection assay with the vascular pathogen Fusarium oxysporum demonstrated that the mutant has enhanced resistance to this pathogen compared with wild type plants. Taken together our results suggest that crk10-A397T is a gain-of-function allele of CRK10, the first such mutant to have been identified for a CRK in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Regulação da Expressão Gênica de Plantas , Mutação Puntual , Proteínas Quinases/genética , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo
3.
Gut ; 70(12): 2273-2282, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33328245

RESUMO

OBJECTIVE: Necrotising enterocolitis (NEC) is a devastating intestinal disease primarily affecting preterm infants. The underlying mechanisms are poorly understood: mother's own breast milk (MOM) is protective, possibly relating to human milk oligosaccharide (HMO) and infant gut microbiome interplay. We investigated the interaction between HMO profiles and infant gut microbiome development and its association with NEC. DESIGN: We performed HMO profiling of MOM in a large cohort of infants with NEC (n=33) with matched controls (n=37). In a subset of 48 infants (14 with NEC), we also performed longitudinal metagenomic sequencing of infant stool (n=644). RESULTS: Concentration of a single HMO, disialyllacto-N-tetraose (DSLNT), was significantly lower in MOM received by infants with NEC compared with controls. A MOM threshold level of 241 nmol/mL had a sensitivity and specificity of 0.9 for NEC. Metagenomic sequencing before NEC onset showed significantly lower relative abundance of Bifidobacterium longum and higher relative abundance of Enterobacter cloacae in infants with NEC. Longitudinal development of the microbiome was also impacted by low MOM DSLNT associated with reduced transition into preterm gut community types dominated by Bifidobacterium spp and typically observed in older infants. Random forest analysis combining HMO and metagenome data before disease accurately classified 87.5% of infants as healthy or having NEC. CONCLUSION: These results demonstrate the importance of HMOs and gut microbiome in preterm infant health and disease. The findings offer potential targets for biomarker development, disease risk stratification and novel avenues for supplements that may prevent life-threatening disease.


Assuntos
Enterocolite Necrosante/microbiologia , Enterocolite Necrosante/prevenção & controle , Fezes/microbiologia , Leite Humano/química , Oligossacarídeos/metabolismo , Estudos de Casos e Controles , Feminino , Microbioma Gastrointestinal , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino
4.
Cancer ; 122(14): 2186-96, 2016 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-27142181

RESUMO

BACKGROUND: Despite increasing data on the impact of the microbiome on cancer, the dynamics and role of the microbiome in infection during therapy for acute myelogenous leukemia (AML) are unknown. Therefore, the authors sought to determine correlations between microbiome composition and infectious outcomes in patients with AML who were receiving induction chemotherapy (IC). METHODS: Buccal and fecal specimens (478 samples) were collected twice weekly from 34 patients with AML who were undergoing IC. Oral and stool microbiomes were characterized by 16S ribosomal RNA V4 sequencing using an Illumina MiSeq system. Microbial diversity and genera composition were associated with clinical outcomes. RESULTS: Baseline stool α-diversity was significantly lower in patients who developed infections during IC compared with those who did not (P = .047). Significant decreases in both oral and stool microbial α-diversity were observed over the course of IC, with a linear correlation between α-diversity change at the 2 sites (P = .02). Loss of both oral and stool α-diversity was associated significantly with the receipt of a carbapenem P < 0.001. Domination events by the majority of genera were transient (median duration, 1 sample), whereas the number of domination events by pathogenic genera increased significantly over the course of IC (P = .002). Moreover, patients who lost microbial diversity over the course of IC were significantly more likely to contract a microbiologically documented infection within the 90 days after IC neutrophil recovery (P = .04). CONCLUSIONS: The current data present the largest longitudinal analyses to date of oral and stool microbiomes in patients with AML and suggest that microbiome measurements could assist with the mitigation of infectious complications of AML therapy. Cancer 2016;122:2186-96. © 2016 American Cancer Society.


Assuntos
Microbioma Gastrointestinal , Quimioterapia de Indução/efeitos adversos , Infecções/etiologia , Leucemia Mieloide Aguda/complicações , Adulto , Idoso , Biodiversidade , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Infecções/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Metagenoma , Metagenômica/métodos , Pessoa de Meia-Idade , Prognóstico , RNA Ribossômico 16S/genética , Adulto Jovem
5.
Water Sci Technol ; 73(6): 1287-92, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27003068

RESUMO

An anaerobic/ion exchange (AN-IX) system was developed for recovery and reuse of wastewater nitrogen at point-of-origin. AN-IX combines upflow solids blanket anaerobic treatment with ammonium ion adsorption onto granular natural zeolite. AN-IX operates passively and without energy input. A 57 L empty-bed prototype was operated for 355 days on wastewater primary effluent. Total nitrogen removal exceeded 95% over the first 214 days of operation and ammonia reduction exceeded 99%; accumulation of oxidized nitrogen species (NO3(-) + NO2(-)) was not observed. The wastewater flowrate was increased during the last 35 days of operation to deliberately exhaust the ion exchange media. Spent granular media was removed from the AN-IX prototype and deployed in plant chamber experiments for cultivation of Solanum lycopersicum (cherry tomato). Wastewater nitrogen captured on zeolite was capable of supplying the total growth requirement for nitrogen. Canopy volume and plant flowering and fruiting were higher for wastewater nitrogen than for artificial fertilizer. The AN-IX process is a passive, mechanically simple and reliable system for local-scale nitrogen recovery. AN-IX is modular, scalable, adaptable and can be applied in diverse treatment contexts and recycling scenarios. AN-IX benefits include appropriate technology for local-scale nitrogen recovery, low capital and energy costs, and protection of health and the environment.


Assuntos
Nitrogênio/química , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química , Adsorção , Compostos de Amônio , Fertilizantes , Troca Iônica , Plantas Comestíveis , Reciclagem , Zeolitas
6.
Funct Plant Biol ; 512024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38417910

RESUMO

Black-grass (Alopecurus myosuroides ) is one of the most problematic agricultural weeds of Western Europe, causing significant yield losses in winter wheat (Triticum aestivum ) and other crops through competition for space and resources. Previous studies link black-grass patches to water-retaining soils, yet its specific adaptations to these conditions remain unclear. We designed pot-based waterlogging experiments to compare 13 biotypes of black-grass and six cultivars of wheat. These showed that wheat roots induced aerenchyma when waterlogged whereas aerenchyma-like structures were constitutively present in black-grass. Aerial biomass of waterlogged wheat was smaller, whereas waterlogged black-grass was similar or larger. Variability in waterlogging responses within and between these species was correlated with transcriptomic and metabolomic changes in leaves of control or waterlogged plants. In wheat, transcripts associated with regulation and utilisation of phosphate compounds were upregulated and sugars and amino acids concentrations were increased. Black-grass biotypes showed limited molecular responses to waterlogging. Some black-grass amino acids were decreased and one transcript commonly upregulated was previously identified in screens for genes underpinning metabolism-based resistance to herbicides. Our findings provide insights into the different waterlogging tolerances of these species and may help to explain the previously observed patchiness of this weed's distribution in wheat fields.


Assuntos
Herbicidas , Triticum , Triticum/genética , Triticum/metabolismo , Poaceae/genética , Herbicidas/farmacologia , Herbicidas/metabolismo , Plantas Daninhas , Aminoácidos/metabolismo
7.
Transl Neurodegener ; 12(1): 47, 2023 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-37828541

RESUMO

Amyotrophic lateral sclerosis (ALS) is a poorly treated multifactorial neurodegenerative disease associated with multiple cell types and subcellular organelles. As with other multifactorial diseases, it is likely that drugs will need to target multiple disease processes and cell types to be effective. We review here the role of Janus kinase (JAK)/Signal transducer and activator of transcription (STAT) signalling in ALS, confirm the association of this signalling with fundamental ALS disease processes using the BenevolentAI Knowledge Graph, and demonstrate that inhibitors of this pathway could reduce the ALS pathophysiology in neurons, glia, muscle fibres, and blood cells. Specifically, we suggest that inhibition of the JAK enzymes by approved inhibitors known as Jakinibs could reduce STAT3 activation and modify the progress of this disease. Analysis of the Jakinibs highlights baricitinib as a suitable candidate due to its ability to penetrate the central nervous system and exert beneficial effects on the immune system. Therefore, we recommend that this drug be tested in appropriately designed clinical trials for ALS.


Assuntos
Esclerose Lateral Amiotrófica , Inibidores de Janus Quinases , Doenças Neurodegenerativas , Humanos , Esclerose Lateral Amiotrófica/tratamento farmacológico , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Inibidores de Janus Quinases/uso terapêutico , Sistema Nervoso Central/metabolismo , Janus Quinases/metabolismo , Janus Quinases/uso terapêutico
8.
Vaccines (Basel) ; 10(6)2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35746559

RESUMO

During the current pandemic, the vast majority of COVID-19 patients experienced mild symptoms, but some had a potentially fatal aberrant hyperinflammatory immune reaction characterized by high levels of IL-6 and other cytokines. Modulation of this immune reaction has proven to be the only method of reducing mortality in severe and critical COVID-19. The anti-inflammatory drug baricitinib (Olumiant) has recently been strongly recommended by the WHO for use in COVID-19 patients because it reduces the risk of progressive disease and death. It is a Janus Kinase (JAK) 1/2 inhibitor approved for rheumatoid arthritis which was suggested in early 2020 as a treatment for COVID-19. In this review the AI-assisted identification of baricitinib, its antiviral and anti-inflammatory properties, and efficacy in clinical trials are discussed and compared with those of other immune modulators including glucocorticoids, IL-6 and IL-1 receptor blockers and other JAK inhibitors. Baricitinib inhibits both virus infection and cytokine signalling and is not only important for COVID-19 management but is "non-immunological", and so should remain effective if new SARS-CoV-2 variants escape immune control. The repurposing of baricitinib is an example of how advanced artificial intelligence (AI) can quickly identify new drug candidates that have clinical benefit in previously unsuspected therapeutic areas.

9.
Nat Commun ; 13(1): 3151, 2022 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-35672407

RESUMO

Fungal infections are a major health problem that often begin in the gastrointestinal tract. Gut microbe interactions in early childhood are critical for proper immune responses, yet there is little known about the development of the fungal population from infancy into childhood. Here, as part of the TEDDY (The Environmental Determinants of Diabetes in the Young) study, we examine stool samples of 888 children from 3 to 48 months and find considerable differences between fungi and bacteria. The metagenomic relative abundance of fungi was extremely low but increased while weaning from milk and formula. Overall fungal diversity remained constant over time, in contrast with the increase in bacterial diversity. Fungal profiles had high temporal variation, but there was less variation from month-to-month in an individual than among different children of the same age. Fungal composition varied with geography, diet, and the use of probiotics. Multiple Candida spp. were at higher relative abundance in children than adults, while Malassezia and certain food-associated fungi were lower in children. There were only subtle fungal differences associated with the subset of children that developed islet autoimmunity or type 1 diabetes. Having proper fungal exposures may be crucial for children to establish appropriate responses to fungi and limit the risk of infection: the data here suggests those gastrointestinal exposures are limited and variable.


Assuntos
Diabetes Mellitus Tipo 1 , Probióticos , Adulto , Autoimunidade , Bactérias , Candida , Criança , Pré-Escolar , Fungos , Trato Gastrointestinal/microbiologia , Humanos
10.
Cancer Discov ; 12(2): 416-431, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34551970

RESUMO

Somatic mutations in ACVR1 are found in a quarter of children with diffuse intrinsic pontine glioma (DIPG), but there are no ACVR1 inhibitors licensed for the disease. Using an artificial intelligence-based platform to search for approved compounds for ACVR1-mutant DIPG, the combination of vandetanib and everolimus was identified as a possible therapeutic approach. Vandetanib, an inhibitor of VEGFR/RET/EGFR, was found to target ACVR1 (K d = 150 nmol/L) and reduce DIPG cell viability in vitro but has limited ability to cross the blood-brain barrier. In addition to mTOR, everolimus inhibited ABCG2 (BCRP) and ABCB1 (P-gp) transporters and was synergistic in DIPG cells when combined with vandetanib in vitro. This combination was well tolerated in vivo and significantly extended survival and reduced tumor burden in an orthotopic ACVR1-mutant patient-derived DIPG xenograft model. Four patients with ACVR1-mutant DIPG were treated with vandetanib plus an mTOR inhibitor, informing the dosing and toxicity profile of this combination for future clinical studies. SIGNIFICANCE: Twenty-five percent of patients with the incurable brainstem tumor DIPG harbor somatic activating mutations in ACVR1, but there are no approved drugs targeting the receptor. Using artificial intelligence, we identify and validate, both experimentally and clinically, the novel combination of vandetanib and everolimus in these children based on both signaling and pharmacokinetic synergies.This article is highlighted in the In This Issue feature, p. 275.


Assuntos
Receptores de Ativinas Tipo I/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Tronco Encefálico/tratamento farmacológico , Everolimo/uso terapêutico , Glioma/tratamento farmacológico , Piperidinas/uso terapêutico , Quinazolinas/uso terapêutico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias do Tronco Encefálico/mortalidade , Criança , Pré-Escolar , Reposicionamento de Medicamentos , Everolimo/administração & dosagem , Feminino , Glioma/mortalidade , Humanos , Masculino , Camundongos , Camundongos SCID , Piperidinas/administração & dosagem , Quinazolinas/administração & dosagem , Ratos , Resultado do Tratamento
11.
Water Environ Res ; 83(4): 373-84, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21553593

RESUMO

Enhanced nitrogen removal from stormwater using chabazite, a natural cation exchanger, was evaluated in a pilot-plant biofilter operated for 216 days. A parallel sand filter served as the control. The biofilters were subject to various operating modes including baseline periods of steady flowrate and loading, simulated high flowrate (storm) events following steady flowrates, high flowrates following extended no-flow periods, and with limited influent dissolved oxygen. Under steady-flow operation, chabazite removed 93% of ammonium and sand removed 87%; total inorganic nitrogen was reduced 35% by chabazite versus 15% by sand. In a simulated storm event following steady-flow operation, 97% of cumulative ammonia mass was retained by the chabazite biofilter versus 70% for sand. Following a 40 day no-flow period, the chabazite biofilter retained 98% of influent ammonium in a storm event while sand exhibited high effluent ammonium. Chabazite ammonium retention was high under limited influent dissolved oxygen, verses significant breakthrough by the sand biofilter. Chabazite media provided superior performance resiliency under dynamic conditions that typify stormwater treatment.


Assuntos
Filtração/métodos , Nitrogênio/isolamento & purificação , Zeolitas/química , Espectrofotometria Ultravioleta
12.
Aliment Pharmacol Ther ; 53(4): 499-509, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33314183

RESUMO

BACKGROUND: Dietary fructans may worsen gastrointestinal symptoms in children with irritable bowel syndrome (IBS). AIM: To determine whether gut microbiome composition and function are associated with childhood IBS fructan-induced symptoms. METHODS: Faecal samples were collected from 38 children aged 7-17 years with paediatric Rome III IBS, who previously completied a double-blind, randomised, placebo-controlled crossover (fructan vs maltodextrin) trial. Fructan sensitivity was defined as an increase of ≥30% in abdominal pain frequency during the fructan diet. Gut microbial composition was determined via 16Sv4 rDNA sequencing. LEfSe evaluated taxonomic composition differences. Tax4Fun2 predicted microbial fructan metabolic pathways. RESULTS: At baseline, 17 fructan-sensitive (vs 21 fructan-tolerant) subjects had lower alpha diversity (q < 0.05) and were enriched in the genus Holdermania. In contrast, fructan-tolerant subjects were enriched in 14 genera from the class Clostridia. During the fructan diet, fructan-sensitive (vs tolerant) subjects were enriched in both Agathobacter (P = 0.02) and Cyanobacteria (P = 0.0001). In contrast, fructan-tolerant subjects were enriched in three genera from the Clostridia class. Comparing the fructan vs maltodextrin diet, fructan-sensitive subjects had a significantly increased relative abundance of Bifidobacterium (P = 0.02) while fructan-tolerant subjects had increased Anaerostipes (P = 0.03) during the fructan diet. Only fructan-sensitive subjects had a trend towards increased predicted ß-fructofuranosidase during the fructan vs maltodextrin diet. CONCLUSIONS: Fructan-sensitive children with IBS have distinct gut microbiome signatures. These microbiome signatures differ both at baseline and in response to a fructan challenge.


Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Adolescente , Bifidobacterium , Criança , Fezes , Frutanos , Humanos
13.
Front Pharmacol ; 12: 709856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393789

RESUMO

The onset of the 2019 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic necessitated the identification of approved drugs to treat the disease, before the development, approval and widespread administration of suitable vaccines. To identify such a drug, we used a visual analytics workflow where computational tools applied over an AI-enhanced biomedical knowledge graph were combined with human expertise. The workflow comprised rapid augmentation of knowledge graph information from recent literature using machine learning (ML) based extraction, with human-guided iterative queries of the graph. Using this workflow, we identified the rheumatoid arthritis drug baricitinib as both an antiviral and anti-inflammatory therapy. The effectiveness of baricitinib was substantiated by the recent publication of the data from the ACTT-2 randomised Phase 3 trial, followed by emergency approval for use by the FDA, and a report from the CoV-BARRIER trial confirming significant reductions in mortality with baricitinib compared to standard of care. Such methods that iteratively combine computational tools with human expertise hold promise for the identification of treatments for rare and neglected diseases and, beyond drug repurposing, in areas of biological research where relevant data may be lacking or hidden in the mass of available biomedical literature.

14.
Glob Change Biol Bioenergy ; 13(1): 98-111, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33381230

RESUMO

Flowering in perennial species is directed via complex signalling pathways that adjust to developmental regulations and environmental cues. Synchronized flowering in certain environments is a prerequisite to commercial seed production, and so the elucidation of the genetic architecture of flowering time in Miscanthus and switchgrass could aid breeding in these underdeveloped species. In this context, we assessed a mapping population in Miscanthus and two ecologically diverse switchgrass mapping populations over 3 years from planting. Multiple flowering time quantitative trait loci (QTL) were identified in both species. Remarkably, the most significant Miscanthus and switchgrass QTL proved to be syntenic, located on linkage groups 4 and 2, with logarithm of odds scores of 17.05 and 21.8 respectively. These QTL regions contained three flowering time transcription factors: Squamosa Promoter-binding protein-Like, MADS-box SEPELLATA2 and gibberellin-responsive bHLH137. The former is emerging as a key component of the age-related flowering time pathway.

15.
Cells ; 10(2)2021 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-33668457

RESUMO

The normal composition of the intestinal microbiota is a key factor for maintaining healthy homeostasis, and accordingly, dysbiosis is well known to be present in HIV-1 patients. This article investigates the gut microbiota profile of antiretroviral therapy-naive HIV-1 patients and healthy donors living in Latin America in a cohort of 13 HIV positive patients (six elite controllers, EC, and seven non-controllers, NC) and nine healthy donors (HD). Microbiota compositions in stool samples were determined by sequencing the V3-V4 region of the bacterial 16S rRNA, and functional prediction was inferred using PICRUSt. Several taxa were enriched in EC compared to NC or HD groups, including Acidaminococcus, Clostridium methylpentosum, Barnesiella, Eubacterium coprostanoligenes, and Lachnospiraceae UCG-004. In addition, our data indicate that the route of infection is an important factor associated with changes in gut microbiome composition, and we extend these results by identifying several metabolic pathways associated with each route of infection. Importantly, we observed several bacterial taxa that might be associated with different viral subtypes, such as Succinivibrio, which were more abundant in patients infected by HIV subtype B, and Streptococcus enrichment in patients infected by subtype C. In conclusion, our data brings a significant contribution to the understanding of dysbiosis-associated changes in HIV infection and describes, for the first time, differences in microbiota composition according to HIV subtypes. These results warrant further confirmation in a larger cohort of patients.


Assuntos
Microbioma Gastrointestinal , Infecções por HIV/metabolismo , Infecções por HIV/microbiologia , Redes e Vias Metabólicas , Adulto , Bactérias/classificação , Análise Discriminante , Fezes/microbiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , HIV-1/fisiologia , Humanos , Pessoa de Meia-Idade
16.
BMC Genomics ; 10: 268, 2009 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-19531245

RESUMO

BACKGROUND: Metagenomic sequence data are proving to be a vast resource for the discovery of biological components. Yet analysis of this data to identify functional RNAs lags behind efforts to characterize protein diversity. The genome of 'Candidatus Pelagibacter ubique' HTCC 1062 is the closest match for approximately 20% of marine metagenomic sequence reads. It is also small, contains little non-coding DNA, and has strikingly low GC content. RESULTS: To aid the discovery of RNA motifs within the marine metagenome we exploited the genomic properties of 'Cand. P. ubique' by targeting our search to long intergenic regions (IGRs) with relatively high GC content. Analysis of known RNAs (rRNA, tRNA, riboswitches etc.) shows that structured RNAs are significantly enriched in such IGRs. To identify additional candidate structured RNAs, we examined other IGRs with similar characteristics from 'Cand. P. ubique' using comparative genomics approaches in conjunction with marine metagenomic data. Employing this strategy, we discovered four candidate structured RNAs including a new riboswitch class as well as three additional likely cis-regulatory elements that precede genes encoding ribosomal proteins S2 and S12, and the cytoplasmic protein component of the signal recognition particle. We also describe four additional potential RNA motifs with few or no examples occurring outside the metagenomic data. CONCLUSION: This work begins the process of identifying functional RNA motifs present in the metagenomic data and illustrates how existing completed genomes may be used to aid in this task.


Assuntos
Alphaproteobacteria/genética , Genômica/métodos , RNA Bacteriano/genética , Análise de Sequência de RNA/métodos , Composição de Bases , Sequência de Bases , Sequência Consenso , Sequência Conservada , Genoma Bacteriano , Dados de Sequência Molecular , Conformação de Ácido Nucleico , Alinhamento de Sequência
17.
Biotechnol Bioeng ; 99(4): 830-45, 2008 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-17705250

RESUMO

The redox control bioreactor (RCB) is a new hollow fiber membrane bioreactor (HFMBR) design in which oxygen and hydrogen gases are provided simultaneously through separate arrays of juxtaposed hollow fiber (HF) membranes. This study applied the RCB for completely autotrophic conversion of ammonia to N(2) through nitrification with O(2) and denitrification using hydrogen as an electron donor (i.e., autohydrogentrophic denitrification). The hypothesis of this research was that efficient biofilm utilization of O(2) and H(2) at respective HFs would limit transport of these gases to bulk fluid, thereby enabling completely autotrophic ammonia conversion to N(2) through the co-occurrence of ammonia oxidation (O(2)-HF biofilms) and autohydrogenotrophic denitrification (H(2)-HF biofilms). A prototype RCB was fabricated and operated for 215 days on a synthetic, organic-free feedstream containing 217 mg L(-1) NH(4)(+)-N. When O(2) and H(2) were simultaneously supplied, the RCB achieved a steady NH(4)(+)-N removal flux of 5.8 g m(-2) day(-1) normalized to O(2)-HF surface area with a concomitant removal flux of 4.4 g m(-2) day(-1) (NO(3)(-))+NO(2)(-))-N based on H(2)-HF surface area. The significance of H(2) supply was confirmed by an increase in effluent NO(3)(-)-N when H(2) supply was discontinued and a decline in NO(3)(-)-N when H(2) supply was restarted. Increases in H(2) pressure caused decreased ammonia utilization, suggesting that excess H(2) interfered with nitrification. Microprobe profiling across radial transects revealed significant gradients in dissolved O(2) on spatial scales of 1 mm or less. Physiological and molecular analysis of biofilms confirmed that structurally and functionally distinct biofilms developed on adjacent, juxtaposed fibers.


Assuntos
Amônia/metabolismo , Bactérias Aeróbias/metabolismo , Reatores Biológicos/microbiologia , Oxigênio/metabolismo , Poluentes Químicos da Água/metabolismo , Purificação da Água/instrumentação , Desenho de Equipamento , Análise de Falha de Equipamento , Oxirredução , Purificação da Água/métodos
19.
PLoS One ; 13(4): e0194100, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29694348

RESUMO

The oral microbiome has been linked to a number of chronic inflammatory conditions, including obesity, diabetes, periodontitis, and cancers of the stomach and liver. These conditions disproportionately affect Mexican American women, yet few studies have examined the oral microbiota in this at-risk group. We characterized the 16S rDNA oral microbiome in 369 non-smoking women enrolled in the MD Anderson Mano a Mano Mexican American Cohort Study. Lower bacterial diversity, a potential indicator of oral health, was associated with increased age and length of US residency among recent immigrants. Grouping women by overarching bacterial community type (e.g., "Streptococcus," "Fusobacterium," and "Prevotella" clusters), we observed differences across a number of acculturation-related variables, including nativity, age at immigration, time in the US, country of longest residence, and a multi-dimensional acculturation scale. Participants in the cluster typified by higher abundance of Streptococcus spp. exhibited the lowest bacterial diversity and appeared the most acculturated as compared to women in the "Prevotella" group. Computationally-predicted functional analysis suggested the Streptococcus-dominated bacterial community had greater potential for carbohydrate metabolism while biosynthesis of essential amino acids and nitrogen metabolism prevailed among the Prevotella-high group. Findings suggest immigration and adaption to life in the US, a well-established mediator of disease risk, is associated with differences in oral microbial profiles in Mexican American women. These results warrant further investigation into the joint and modifying effects of acculturation and oral bacteria on the health of Mexican American women and other immigrant populations. The oral microbiome presents an easily accessible biomarker of disease risk, spanning biological, behavioral, and environmental factors.


Assuntos
Aculturação , Fusobacterium/isolamento & purificação , Americanos Mexicanos , Microbiota/fisiologia , Boca/microbiologia , Prevotella/isolamento & purificação , Streptococcus/isolamento & purificação , Adulto , Idoso , Emigrantes e Imigrantes , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
20.
PeerJ ; 6: e4693, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29736335

RESUMO

BACKGROUND: The use of electronic cigarettes (ECs) has increased drastically over the past five years, primarily as an alternative to smoking tobacco cigarettes. However, the adverse effects of acute and long-term use of ECs on the microbiota have not been explored. In this pilot study, we sought to determine if ECs or tobacco smoking alter the oral and gut microbiota in comparison to non-smoking controls. METHODS: We examined a human cohort consisting of 30 individuals: 10 EC users, 10 tobacco smokers, and 10 controls. We collected cross-sectional fecal, buccal swabs, and saliva samples from each participant. All samples underwent V4 16S rRNA gene sequencing. RESULTS: Tobacco smoking had a significant effect on the bacterial profiles in all sample types when compared to controls, and in feces and buccal swabs when compared to EC users. The most significant associations were found in the gut, with an increased relative abundance of Prevotella (P = 0.006) and decreased Bacteroides (P = 0.036) in tobacco smokers. The Shannon diversity was also significantly reduced (P = 0.009) in fecal samples collected from tobacco smokers compared to controls. No significant difference was found in the alpha diversity, beta-diversity or taxonomic relative abundances between EC users and controls. DISCUSSION: From a microbial ecology perspective, the current pilot data demonstrate that the use of ECs may represent a safer alternative compared to tobacco smoking. However, validation in larger cohorts and greater understanding of the short and long-term impact of EC use on microbiota composition and function is warranted.

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