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1.
Nucleic Acids Res ; 50(6): 3128-3141, 2022 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-35286381

RESUMO

Alternative splicing is frequently involved in the diversification of protein function and can also be modulated for therapeutic purposes. Here we develop a predictive model, called Exon ByPASS (predicting Exon skipping Based on Protein amino acid SequenceS), to assess the criticality of exon inclusion based solely on information contained in the amino acid sequence upstream and downstream of the exon junctions. By focusing on protein sequence, Exon ByPASS predicts exon skipping independent of tissue and species in the absence of any intronic information. We validate model predictions using transcriptomic and proteomic data and show that the model can capture exon skipping in different tissues and species. Additionally, we reveal potential therapeutic opportunities by predicting synthetically skippable exons and neo-junctions arising in cancer cells.


Assuntos
Processamento Alternativo , Proteômica , Sequência de Aminoácidos , Éxons/genética , Íntrons
2.
Clin Psychol Psychother ; 30(3): 548-565, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36478339

RESUMO

BACKGROUND: Women are likely to suffer from maternal depression due to childbirth difficulties and parenting responsibilities, leading to long-term negative consequences on their children and families. British mothers of African/Caribbean origin uptake of mental healthcare is low due to the lack of access to culturally appropriate care. METHODS: A mixed-methods randomized controlled feasibility trial was adopted to test the appropriateness and acceptability of Learning Through Play plus Culturally adapted Cognitive Behaviour Therapy (LTP+CaCBT) for treating maternal depression compared with Psychoeducation (PE). Mothers (N = 26) aged 20-55 were screened for depression using the Patient Health Questionnaire (PHQ-9). Those who scored >5 on PHQ-9 were further interviewed using the Revised Clinical Interview Schedule to confirm the diagnosis and randomized into LTP+CaCBT (n = 13) or PE (n = 13) groups. Assessments were taken at baseline, end of the intervention at 3- and 6-months post-randomization. N = 2 focus groups (LTP+CaCBT, n = 12; PE, n = 7) and N = 8 individual interviews were conducted (LTP+CaCBT, n = 4; PE, n = 4). RESULTS: The LTP+CaCBT group showed higher acceptability, feasibility and satisfaction levels than the PE group. Participants experienced the intervention as beneficial to their parenting skills with reduced depression and anxiety in the LTP+CaCBT compared to the PE group. CONCLUSIONS: This is the first feasibility trial of an integrated online parenting intervention for British African and Caribbean mothers. The results indicated that culturally adapted LTP+CaCBT is acceptable and feasible. There is a need to study the clinical and cost-effectiveness of LTP+CaCBT in an appropriately powered randomized control trial and include the child's outcomes. TRIAL REGISTRATION: www. CLINICALTRIALS: gov (no. NCT04820920).


Assuntos
Depressão , Mães , Criança , Humanos , Feminino , Mães/psicologia , Depressão/terapia , Estudos de Viabilidade , Intervenção Psicossocial , Resultado do Tratamento , Região do Caribe
3.
Nanomedicine ; 40: 102488, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34748964

RESUMO

The goal of this study was to evaluate hepatocyte-specific gene editing, via systemic administration of hyaluronic acid (HA)-based nanoparticles in naïve CD-1 mice. Using HA-poly(ethylene imine) (HA-PEI) and HA-PEI-mannose nanoparticles with differential mannose density (1X and 2X), we have evaluated systemic biodistribution and hepatocyte-specific delivery using IVIS imaging and flow cytometry. Additionally, we have investigated hepatocyte-specific delivery and transfection of CRISPR/Cas9 gene editing plasmid and eGFP gene payload to integrate at the Rosa26 locus. IVIS imaging showed uptake of HA-PEI nanoparticles primarily by the liver, and with addition of mannose at different concentrations, the nanoparticles showed increased uptake in both the liver and spleen. HA-PEI-mannose nanoparticles showed 55-65% uptake by hepatocytes, along with uptake by resident macrophage regardless of the mannose concentration. One of two gRNA targets showed 15% genome editing and obtained similar results for all three nanoparticle formulations. Cells positive for our gene payload were greatest with HA-PEI-mannose-1X nanoparticles where 16.2% of cells were GFP positive. The results were encouraging as proof of concept for the development of a non-viral biodegradable and biocompatible polymeric delivery system for gene editing specifically targeting hepatocytes upon systemic administration.


Assuntos
Edição de Genes , Nanopartículas , Animais , Sistemas CRISPR-Cas/genética , Edição de Genes/métodos , Hepatócitos , Ácido Hialurônico , Camundongos , Distribuição Tecidual
4.
PLoS Genet ; 15(12): e1008508, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31815936

RESUMO

Zinc is essential for cellular functions as it is a catalytic and structural component of many proteins. In contrast, cadmium is not required in biological systems and is toxic. Zinc and cadmium levels are closely monitored and regulated as their excess causes cell stress. To maintain homeostasis, organisms induce metal detoxification gene programs through stress responsive transcriptional regulatory complexes. In Caenorhabditis elegans, the MDT-15 subunit of the evolutionarily conserved Mediator transcriptional coregulator is required to induce genes upon exposure to excess zinc and cadmium. However, the regulatory partners of MDT-15 in this response, its role in cellular and physiological stress adaptation, and the putative role for mammalian MED15 in the metal stress responses remain unknown. Here, we show that MDT-15 interacts physically and functionally with the Nuclear Hormone Receptor HIZR-1 to promote molecular, cellular, and organismal adaptation to cadmium and excess zinc. Using gain- and loss-of-function mutants and qRT-PCR and reporter analysis, we find that mdt-15 and hizr-1 cooperate to induce zinc and cadmium responsive genes. Moreover, the two proteins interact physically in yeast-two-hybrid assays and this interaction is enhanced by the addition of zinc or cadmium, the former a known ligand of HIZR-1. Functionally, mdt-15 and hizr-1 mutants show defective storage of excess zinc in the gut and are hypersensitive to zinc-induced reductions in egg-laying. Furthermore, mdt-15 but not hizr-1 mutants are hypersensitive to cadmium-induced reductions in egg-laying, suggesting potential divergence of regulatory pathways. Lastly, mammalian MDT-15 orthologs bind genomic regulatory regions of metallothionein and zinc transporter genes in a cadmium and zinc-stimulated fashion, and human MED15 is required to induce a metallothionein gene in lung adenocarcinoma cells exposed to cadmium. Collectively, our data show that mdt-15 and hizr-1 cooperate to regulate cadmium detoxification and zinc storage and that this mechanism is at least partially conserved in mammals.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Fator 4 Nuclear de Hepatócito/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Zinco/toxicidade , Animais , Caenorhabditis elegans/efeitos dos fármacos , Proteínas de Caenorhabditis elegans/genética , Proteínas de Transporte/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Fator 4 Nuclear de Hepatócito/genética , Humanos , Metalotioneína/genética , Mutação , Regiões Promotoras Genéticas , Receptores Citoplasmáticos e Nucleares/genética , Estresse Fisiológico , Fatores de Transcrição/genética , Técnicas do Sistema de Duplo-Híbrido
5.
FASEB J ; 34(7): 9156-9179, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32413239

RESUMO

Pseudomonas aeruginosa infection elicits the production of cytotoxic amyloids from lung endothelium, yet molecular mechanisms of host-pathogen interaction that underlie the amyloid production are not well understood. We examined the importance of type III secretion system (T3SS) effectors in the production of cytotoxic amyloids. P aeruginosa possessing a functional T3SS and effectors induced the production and release of cytotoxic amyloids from lung endothelium, including beta amyloid, and tau. T3SS effector intoxication was sufficient to generate cytotoxic amyloid release, yet intoxication with exoenzyme Y (ExoY) alone or together with exoenzymes S and T (ExoS/T/Y) generated the most virulent amyloids. Infection with lab and clinical strains engendered cytotoxic amyloids that were capable of being propagated in endothelial cell culture and passed to naïve cells, indicative of a prion strain. Conversely, T3SS-incompetent P aeruginosa infection produced non-cytotoxic amyloids with antimicrobial properties. These findings provide evidence that (1) endothelial intoxication with ExoY is sufficient to elicit self-propagating amyloid cytotoxins during infection, (2) pulmonary endothelium contributes to innate immunity by generating antimicrobial amyloids in response to bacterial infection, and (3) ExoY contributes to the virulence arsenal of P aeruginosa through the subversion of endothelial amyloid host-defense to promote a lung endothelial-derived cytotoxic proteinopathy.


Assuntos
Amiloide/química , Antibacterianos/farmacologia , Células Endoteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Príons/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/isolamento & purificação , Animais , Proteínas de Bactérias/imunologia , Citotoxinas/farmacologia , Células Endoteliais/imunologia , Células Endoteliais/microbiologia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Pulmão/imunologia , Pulmão/microbiologia , Masculino , Infecções por Pseudomonas/imunologia , Infecções por Pseudomonas/microbiologia , Ratos , Ratos Endogâmicos F344 , Ratos Sprague-Dawley , Virulência/efeitos dos fármacos
6.
Microb Ecol ; 81(3): 601-616, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33150499

RESUMO

Despite being the largest estuary on the west coast of North America, no in-depth survey of microbial communities in San Francisco Bay (SFB) waters currently exists. In this study, we analyze bacterioplankton and archaeoplankton communities at several taxonomic levels and spatial extents (i.e., North versus South Bay) to reveal patterns in alpha and beta diversity. We assess communities using high-throughput sequencing of the 16S rRNA gene in 177 water column samples collected along a 150-km transect over a 2-year monthly time-series. In North Bay, the microbial community is strongly structured by spatial salinity changes while in South Bay seasonal variations dominate community dynamics. Along the steep salinity gradient in North Bay, we find that operational taxonomic units (OTUs; 97% identity) have higher site specificity than at coarser taxonomic levels and turnover ("species" replacement) is high, revealing a distinct brackish community (in oligo-, meso-, and polyhaline samples) from fresh and marine end-members. At coarser taxonomic levels (e.g., phylum, class), taxa are broadly distributed across salinity zones (i.e., present/abundant in a large number of samples) and brackish communities appear to be a mix of fresh and marine communities. We also observe variations in brackish communities between samples with similar salinities, likely related to differences in water residence times between North and South Bay. Throughout SFB, suspended particulate matter is positively correlated with richness and influences changes in beta diversity. Within several abundant groups, including the SAR11 clade (comprising up to 30% of reads in a sample), OTUs appear to be specialized to a specific salinity range. Some other organisms also showed pronounced seasonal abundance, including Synechococcus, Ca. Actinomarina, and Nitrosopumilus-like OTUs. Overall, this study represents the first in-depth spatiotemporal survey of SFB microbial communities and provides insight into how planktonic microorganisms have specialized to different niches along the salinity gradient.


Assuntos
Archaea , Plâncton , Archaea/genética , Baías , Plâncton/genética , RNA Ribossômico 16S/genética , São Francisco
7.
BMC Womens Health ; 21(1): 83, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637070

RESUMO

BACKGROUND: Maternal depression is a leading cause of disease burden for women worldwide; however, there are ethnic inequalities in access to psychological interventions in high-income countries (HICs). Culturally appropriate interventions might prove beneficial for African and Caribbean women living in HICs as ethnic minorities. METHODS: The review strategy was formulated using the PICo (Population, phenomenon of Interest, and Context) framework with Boolean operators (AND/OR/NOT) to ensure rigour in the use of search terms ("postpartum depression", "maternal depression", "postnatal depression", "perinatal depression" "mental health", "psychotherapy" "intervention", "treatment", "black Caribbean", "black African", "mothers" and "women"). Five databases, including Scopus, PsycINFO, Applied Social Science Index and Abstracts (ASSIA), ProQuest Central and Web of Science, were searched for published articles between 2000 and July 2020. 13 studies met the inclusion criteria, and the relevant data extracted were synthesised and thematically analysed. RESULTS: Data syntheses and analyses of included studies produced four themes, including (1) enhance parenting confidence and self-care; (2) effective mother-child interpersonal relationship; (3) culturally appropriate maternal care; and (4) internet-mediated care for maternal depression. CONCLUSION: In the quest to address maternal mental health disparities among mothers of African and Caribbean origin in HICs, the authors recommend culturally adapted psychological interventions to be tested in randomised control trials.


Assuntos
Depressão , Intervenção Psicossocial , Região do Caribe , Criança , Depressão/terapia , Feminino , Humanos , Saúde Mental , Relações Mãe-Filho , Gravidez
8.
Microb Ecol ; 80(4): 778-792, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32535638

RESUMO

Subsurface microbial communities mediate biogeochemical transformations that drive both local and ecosystem-level cycling of essential elements, including nitrogen. However, their study has been largely limited to the deep ocean, terrestrial mines, caves, and topsoils (< 30 cm). Here, we present regional insights into the microbial ecology of aerobic ammonia oxidation within the terrestrial subsurface of five semi-arid riparian sites spanning a 900-km N-S transect. We sampled sediments, profiled communities to depths of ≤ 10 m, and compared them to reveal trends regionally within and surrounding the Upper Colorado River Basin (CRB). The diversity and abundance of ammonia-oxidizing microbial communities were evaluated in the context of subsurface geochemistry by applying a combination of amoA (encoding ammonia monooxygenase subunit A) gene sequencing, quantitative PCR, and geochemical techniques. Analysis of 898 amoA sequences from ammonia-oxidizing archaea (AOA) and bacteria (AOB) revealed extensive ecosystem-scale diversity, including archaeal amoA sequences from four of the five major AOA lineages currently found worldwide as well as distinct AOA ecotypes associated with naturally reduced zones (NRZs) and hydrogeochemical zones (unsaturated, capillary fringe, and saturated). Overall, AOA outnumber AOB by 2- to 5000-fold over this regional scale, suggesting that AOA may play a prominent biogeochemical role in nitrification within terrestrial subsurface sediments.


Assuntos
Amônia/metabolismo , Archaea/fisiologia , Microbiota/fisiologia , Microbiologia do Solo , Archaea/isolamento & purificação , Colorado , Ecossistema , Inundações , New Mexico , Oxirredução , Wyoming
9.
Environ Microbiol ; 21(11): 4032-4045, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31330081

RESUMO

Ammonia-oxidizing archaea (AOA) of the phylum Thaumarchaeota are key players in nutrient cycling, yet large gaps remain in our understanding of their ecology and metabolism. Despite multiple lines of evidence pointing to a central role for copper-containing nitrite reductase (NirK) in AOA metabolism, the thaumarchaeal nirK gene is rarely studied in the environment. In this study, we examine the diversity of nirK in the marine pelagic environment, in light of previously described ecological patterns of pelagic thaumarchaeal populations. Phylogenetic analyses show that nirK better resolves diversification patterns of marine Thaumarchaeota, compared to the conventionally used marker gene amoA. Specifically, we demonstrate that the three major phylogenetic clusters of marine nirK correspond to the three 'ecotype' populations of pelagic Thaumarchaeota. In this context, we further examine the relative distributions of the three variant groups in metagenomes and metatranscriptomes representing two depth profiles in coastal Monterey Bay. Our results reveal that nirK effectively tracks the dynamics of thaumarchaeal ecotype populations, particularly finer-scale diversification patterns within major lineages. We also find evidence for multiple copies of nirK per genome in a fraction of thaumarchaeal cells in the water column, which must be taken into account when using it as a molecular marker.


Assuntos
Archaea/classificação , Archaea/genética , Baías/microbiologia , Metabolismo Energético/genética , Nitrito Redutases/genética , Amônia/metabolismo , Archaea/metabolismo , Ecótipo , Marcadores Genéticos/genética , Variação Genética/genética , Nitrito Redutases/metabolismo , Oxirredução , Filogenia
10.
Environ Microbiol ; 19(12): 4897-4912, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28892301

RESUMO

Denitrification is a dominant nitrogen loss process in the sediments of San Francisco Bay. In this study, we sought to understand the ecology of denitrifying bacteria by using next-generation sequencing (NGS) to survey the diversity of a denitrification functional gene, nirS (encoding cytchrome-cd1 nitrite reductase), along the salinity gradient of San Francisco Bay over the course of a year. We compared our dataset to a library of nirS sequences obtained previously from the same samples by standard PCR cloning and Sanger sequencing, and showed that both methods similarly demonstrated geography, salinity and, to a lesser extent, nitrogen, to be strong determinants of community composition. Furthermore, the depth afforded by NGS enabled novel techniques for measuring the association between environment and community composition. We used Random Forests modelling to demonstrate that the site and salinity of a sample could be predicted from its nirS sequences, and to identify indicator taxa associated with those environmental characteristics. This work contributes significantly to our understanding of the distribution and dynamics of denitrifying communities in San Francisco Bay, and provides valuable tools for the further study of this key N-cycling guild in all estuarine systems.


Assuntos
Bactérias/classificação , Bactérias/metabolismo , Baías/microbiologia , Meio Ambiente , Sedimentos Geológicos/microbiologia , Nitrito Redutases/genética , Bactérias/genética , Sequência de Bases , Desnitrificação/genética , Geografia , Óxido Nitroso/metabolismo , Salinidade , São Francisco , Análise de Sequência de DNA
11.
Ecology ; 98(4): 1117-1129, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28130777

RESUMO

The supply of nitrogen (N) constrains primary productivity in many ecosystems, raising the question "what controls the availability and cycling of N"? As a step toward answering this question, we evaluated N cycling processes and aspects of their regulation on a climate gradient on Kohala Volcano, Hawaii, USA. The gradient extends from sites receiving <300 mm/yr of rain to those receiving >3,000 mm/yr, and the pedology and dynamics of rock-derived nutrients in soils on the gradient are well understood. In particular, there is a soil process domain at intermediate rainfall within which ongoing weathering and biological uplift have enriched total and available pools of rock-derived nutrients substantially; sites at higher rainfall than this domain are acid and infertile as a consequence of depletion of rock-derived nutrients, while sites at lower rainfall are unproductive and subject to wind erosion. We found elevated rates of potential net N mineralization in the domain where rock-derived nutrients are enriched. Higher-rainfall sites have low rates of potential net N mineralization and high rates of microbial N immobilization, despite relatively high rates of gross N mineralization. Lower-rainfall sites have moderately low potential net N mineralization, relatively low rates of gross N mineralization, and rates of microbial N immobilization sufficient to sequester almost all the mineral N produced. Bulk soil δ15 N also varied along the gradient, from +4‰ at high rainfall sites to +14‰ at low rainfall sites, indicating differences in the sources and dynamics of soil N. Our analysis shows that there is a strong association between N cycling and soil process domains that are defined using soil characteristics independent of N along this gradient, and that short-term controls of N cycling can be understood in terms of the supply of and demand for N.


Assuntos
Clima , Ciclo do Nitrogênio , Havaí , Nitrogênio , Solo
12.
Microb Ecol ; 73(2): 271-284, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27709247

RESUMO

Denitrifying bacteria play a critical role in the estuarine nitrogen cycle. Through the transformation of nitrate into nitrogen gas, these organisms contribute to the loss of bioavailable (i.e., fixed) nitrogen from low-oxygen environments such as estuary sediments. Denitrifiers have been shown to vary in abundance and diversity across the spatial environmental gradients that characterize estuaries, such as salinity and nitrogen availability; however, little is known about how their communities change in response to temporal changes in those environmental properties. Here, we present a 1-year survey of sediment denitrifier communities along the estuarine salinity gradient of San Francisco Bay. We used quantitative PCR and sequencing of functional genes coding for a key denitrifying enzyme, dissimilatory nitrite reductase, to compare two groups of denitrifiers: those with nirK (encoding copper-dependent nitrite reductase) and those with nirS (encoding the cytochrome-cd 1-dependent variant). We found that nirS was consistently more abundant and more diverse than nirK in all parts of the estuary. The abundances of the two genes were tightly linked across space but differed temporally, with nirK peaking when temperature was low and nirS peaking when nitrate was high. Likewise, the diversity and composition of nirK- versus nirS-type communities differed in their responses to seasonal variations, though both were strongly determined by site. Furthermore, our sequence libraries detected deeply branching clades with no cultured isolates, evidence of enormous diversity within the denitrifiers that remains to be explored.


Assuntos
Bactérias/genética , Biodiversidade , Sedimentos Geológicos/microbiologia , Nitrito Redutases/genética , Água do Mar/microbiologia , Amônia/metabolismo , Sequência de Bases , Baías/microbiologia , Grupo dos Citocromos c , Citocromos/genética , DNA Bacteriano , Desnitrificação/genética , Estuários , Genes Bacterianos , Sedimentos Geológicos/química , Nitratos/metabolismo , Nitrogênio/metabolismo , Filogenia , Reação em Cadeia da Polimerase/métodos , RNA Ribossômico 16S/genética , Salinidade , São Francisco , Água do Mar/química , Temperatura
13.
Opt Express ; 24(17): 19881-94, 2016 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-27557264

RESUMO

This paper documents the accuracy and precision of the U. S. Air Force Research Laboratory APCL laser polarimeter in arbitrary bistatic geometries at the three laser wavelengths 633nm, 1064nm, and 1550nm. The difference between measured and theoretical-truth Mueller matrices of calibration components is used as the calibration metric and justified relative to block ellipsometer calibration methods. Calibration of the polarimeter ellipsometry mode is demonstrated first, at quasi-monostatic and large bistatic angles, employing a metallic mirror and a dielectric window as the calibration component, respectively, the latter in order to avoid uncertainty in the retardance of typical metallic mirrors at large incident angles. This uncertainty is demonstrated in measurements of COTS protected-silver mirrors from two vendors, revealing an approximately λ/8 retardance difference, for reflection through 90°, between nominally-identical mirrors from the two vendors. Polarimeter calibration is finally extended beyond ellipsometry by calibrating depolarization measurements using a new technique employing ensembles of polarized states as calibration components.

14.
Microb Ecol ; 69(1): 13-24, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25038845

RESUMO

The primary objective of this study was to gain an understanding of how key microbial communities involved in nitrogen cycling in estuarine sediments vary over a 12-month period. Furthermore, we sought to determine whether changes in the size of these communities are related to, or indicative of, seasonal patterns in fixed nitrogen dynamics in Elkhorn Slough--a small, agriculturally impacted estuary with a direct connection to Monterey Bay. We assessed sediment and pore water characteristics, abundance of functional genes for nitrification (bacterial and archaeal amoA, encoding ammonia monooxygenase subunit A) and denitrification (nirS and nirK, encoding nitrite reductase), and measurements of potential nitrification and denitrification activities at six sites. No seasonality in the abundance of denitrifier or ammonia oxidizer genes was observed. A strong association between potential nitrification activity and the size of ammonia-oxidizing bacterial communities was observed across the estuary. In contrast, ammonia-oxidizing archaeal abundances remained relatively constant in space and time. Unlike many other estuaries, salinity does not appear to regulate the distribution of ammonia-oxidizing communities in Elkhorn Slough. Instead, their distributions appear to be governed over two different time scales. Long-term niche characteristics selected for the gross size of archaeal and bacterial ammonia-oxidizing communities, yet covariation in their abundances between monthly samples suggests that they respond in a similar manner to short-term changes in their environment. Abundances of denitrifier and ammonia oxidizer genes also covaried, but site-specific differences in this relationship suggest differing levels of interaction (or coupling) between nitrification and denitrification.


Assuntos
Amônia/metabolismo , Sedimentos Geológicos/microbiologia , Desnitrificação , Dados de Sequência Molecular , Oxirredutases/metabolismo
15.
Appl Microbiol Biotechnol ; 98(10): 4723-36, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24553968

RESUMO

Wastewater treatment plants use a variety of bioreactor types and configurations to remove organic matter and nutrients. Little is known regarding the effects of different configurations and within-plant immigration on microbial community dynamics. Previously, we found that the structure of ammonia-oxidizing bacterial (AOB) communities in a full-scale dispersed growth activated sludge bioreactor correlated strongly with levels of NO2 (-) entering the reactor from an upstream trickling filter. Here, to further examine this puzzling association, we profile within-plant microbial biogeography (spatial variation) and test the hypothesis that substantial microbial immigration occurs along a transect (raw influent, trickling filter biofilm, trickling filter effluent, and activated sludge) at the same full-scale wastewater treatment plant. AOB amoA gene abundance increased >30-fold between influent and trickling filter effluent concomitant with NO2 (-) production, indicating unexpected growth and activity of AOB within the trickling filter. Nitrosomonas europaea was the dominant AOB phylotype in trickling filter biofilm and effluent, while a distinct "Nitrosomonas-like" lineage dominated in activated sludge. Prior time series indicated that this "Nitrosomonas-like" lineage was dominant when NO2 (-) levels in the trickling filter effluent (i.e., activated sludge influent) were low, while N. europaea became dominant in the activated sludge when NO2 (-) levels were high. This is consistent with the hypothesis that NO2 (-) production may cooccur with biofilm sloughing, releasing N. europaea from the trickling filter into the activated sludge bioreactor. Phylogenetic microarray (PhyloChip) analyses revealed significant spatial variation in taxonomic diversity, including a large excess of methanogens in the trickling filter relative to activated sludge and attenuation of Enterobacteriaceae across the transect, and demonstrated transport of a highly diverse microbial community via the trickling filter effluent to the activated sludge bioreactor. Our results provide compelling evidence that substantial immigration between coupled process units occurs and may exert significant influence over microbial community dynamics within staged bioreactors.


Assuntos
Reatores Biológicos/microbiologia , Biota , Águas Residuárias/microbiologia , Purificação da Água , Análise por Conglomerados , Dados de Sequência Molecular , Nitritos/análise , Oxirredutases/genética , Filogenia , Análise de Sequência de DNA , Águas Residuárias/química
16.
Eplasty ; 24: e20, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846498

RESUMO

Infantile hemangiomas are commonly encountered at all levels of medical practice. Clinicians should be aware of their typical clinical history and findings in order to expedite early diagnosis and management. It is also necessary to be aware of differential diagnoses that may mimic infantile hemangiomas but have a more concerning prognosis. The objective of this report is to describe the clinical case of one such mimic, dermatofibrosarcoma protuberans. This report highlights key clinical findings of infantile hemangiomas, while also identifying "red flags" that necessitate urgent additional investigations and referral to a multidisciplinary team. Additionally, key features in the management of both infantile hemangiomas and extremity masses are discussed.

17.
mSystems ; : e0031424, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940520

RESUMO

We use metagenome-assembled genomes (MAGs) to understand single-carbon (C1) compound-cycling-particularly methane-cycling-microorganisms in montane riparian floodplain sediments. We generated 1,233 MAGs (>50% completeness and <10% contamination) from 50- to 150-cm depth below the sediment surface capturing the transition between oxic, unsaturated sediments and anoxic, saturated sediments in the Slate River (SR) floodplain (Crested Butte, CO, USA). We recovered genomes of putative methanogens, methanotrophs, and methylotrophs (n = 57). Methanogens, found only in deep, anoxic depths at SR, originate from three different clades (Methanoregulaceae, Methanotrichaceae, and Methanomassiliicoccales), each with a different methanogenesis pathway; putative methanotrophic MAGs originate from within the Archaea (Candidatus Methanoperedens) in anoxic depths and uncultured bacteria (Ca. Binatia) in oxic depths. Genomes for canonical aerobic methanotrophs were not recovered. Ca. Methanoperedens were exceptionally abundant (~1,400× coverage, >50% abundance in the MAG library) in one sample that also contained aceticlastic methanogens, indicating a potential C1/methane-cycling hotspot. Ca. Methylomirabilis MAGs from SR encode pathways for methylotrophy but do not harbor methane monooxygenase or nitrogen reduction genes. Comparative genomic analysis supports that one clade within the Ca. Methylomirabilis genus is not methanotrophic. The genetic potential for methylotrophy was widespread, with over 10% and 19% of SR MAGs encoding a methanol dehydrogenase or substrate-specific methyltransferase, respectively. MAGs from uncultured Thermoplasmata archaea in the Ca. Gimiplasmatales (UBA10834) contain pathways that may allow for anaerobic methylotrophic acetogenesis. Overall, MAGs from SR floodplain sediments reveal a potential for methane production and consumption in the system and a robust potential for methylotrophy.IMPORTANCEThe cycling of carbon by microorganisms in subsurface environments is of particular relevance in the face of global climate change. Riparian floodplain sediments contain high organic carbon that can be degraded into C1 compounds such as methane, methanol, and methylamines, the fate of which depends on the microbial metabolisms present as well as the hydrological conditions and availability of oxygen. In the present study, we generated over 1,000 MAGs from subsurface sediments from a montane river floodplain and recovered genomes for microorganisms that are capable of producing and consuming methane and other C1 compounds, highlighting a robust potential for C1 cycling in subsurface sediments both with and without oxygen. Archaea from the Ca. Methanoperedens genus were exceptionally abundant in one sample, indicating a potential C1/methane-cycling hotspot in the Slate River floodplain system.

18.
Front Psychiatry ; 15: 1383990, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38606412

RESUMO

Background: One in every three women worldwide experiences postnatal depression after childbirth, with long-term negative consequences on their children. The mainstream mental healthcare provision for British mothers of African/Caribbean origin is mostly unsuccessful due to a lack of culturally appropriate care. Methods: The study adopts a mixed-methods randomised controlled trial (RCT) design. A 12-session (60 minutes each) of online Learning Through Play plus Culturally adapted Cognitive Behaviour Therapy (LTP+CaCBT) intervention was employed for treating postnatal depression in comparison with psychoeducation (PE). Participants aged 19-53 were screened for depression using the Patient Health Questionnaire (PHQ-9). N=130 participants who scored >5 on PHQ-9 were randomised into LTP+CaCBT (n=65) or PE (n=65) groups. N=12 focus groups (LTP+CaCBT, n=6; PE, n=6) and n=15 individual interviews (LTP+CaCBT, n=8; PE, n=7) were conducted, transcribed verbatim and analysed. Results: Satisfaction with intervention (LTP+CaCBT, 72.9%; PE, 65.2%); retention rates (LTP+CaCBT, 91%; PE, 71%); reduction in postnatal depression was higher in LTP+CaCBT on PHQ-9 Md=1.00 with z= -4.046; compared to PE, Md=1.00 with z= -1.504. Both groups showed reduced levels of anxiety on GAD-7 with no significant difference. Emerging themes from the qualitative findings showed increased positive moods, reduced worries about parenting difficulties and the facilitative role of remote intervention. Conclusions: LTP+CaCBT intervention is culturally appropriate and acceptable and reduces postnatal depression in British mothers of African/Caribbean origin. A fully powered RCT is recommended to evaluate the clinical and cost-effectiveness of LTP+CaCBT, including the child's outcomes compared with routine treatment as usual. Clinical trial registration: www.ClinicalTrials.gov, identifier NCT04820920.

19.
Arch Suicide Res ; : 1-25, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38506246

RESUMO

BACKGROUND: Self-harm and suicidal ideation are increasing public health concerns globally and are paramount in Africa. Therefore, a review of suicidal ideation and self-harm interventions would be beneficial in identifying culturally appropriate interventions for the African context. METHOD: The Population, phenomenon of Interest and Context (PICo) model was adopted to formulate the review strategy. Thus, the Population (Africans), phenomenon of Interest (intervention) and Context (self-harm and suicidal ideation). We used this PICo strategy which is a modified version of PICO for qualitative studies. Framework with Boolean operators (AND/OR/NOT) was further used to ensure rigor through search terms such as ("Suicide" OR "suicidal ideation") AND ("Intervention" OR "Treatment" OR "Therapy" OR "Psychological" OR "Psychosocial" OR "Culturally adapted") AND "Africa" OR "African countries." Six databases were searched (Embase, PsycINFO, ProQuest Central, Cochrane Controlled Trials Register, Medline, and Web of Science) for published articles between 2000 and March 2023. N = 12 studies met the inclusion criteria, and the relevant data extracted were synthesized and thematically analyzed. The review protocol was pre-registered on the PROSPERO Registry (no. CRD42021283795). RESULTS: N = 12 studies met the inclusion criteria, and the following themes emerged from the synthesized literature and analyses of current African approaches to curbing self-harm and suicidal ideation: (a) Western medical and compassion-focused intervention (b) the helpful role of traditional healing and healers (c) psychoeducation and self-help techniques (d) use of technology and a nation-wide approach. CONCLUSION: Self-harm and suicidal ideation are global health concerns. To address this health concern in Africa, the authors recommend culturally adapted psychological interventions to be tested via randomized control trials.

20.
Arch Suicide Res ; : 1-15, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38363148

RESUMO

BACKGROUND: Suicide and self-harm are global disease burden that contributes significantly to years of lost life and mortality. Despite the increasing rates of suicide and self-harm in Nigeria, this topic is understudied. METHODS: A mixed-methods design was adopted. Study 1 interviewed n = 18 participants (n = 11 clinicians; n = 5 patients with a history of self-harm and suicide ideation; and n = 2 caregivers). All interviews were audio-recorded, transcribed verbatim, and analyzed using IPA. Study 2 surveyed n = 562 non-clinical sample about their tolerance toward self-harm and the data was analyzed using One-way ANOVA in SPSS. RESULTS: Study 1 qualitative findings showed substance use, perceived rejection and social isolation were considered predisposing factors for suicide and self-harm. Cultural and religious beliefs shaped help-seeking behaviours. Although Study 2 found no significant differences in demographic characteristics concerning public tolerance toward persons with a history of self-harm, 64% believed that individuals who died by suicide would face punishment after death; 51% believed that victims of attempted suicide are a source of shame to their families; and 33.8% agreed that dying by suicide is the correct behaviour. CONCLUSIONS: Patients with a history of self-harm and suicidal ideation consider family members and close friends as valuable sources of support. Due to the potential clinical implication of cultural and religious beliefs, as shown in the present study's findings, the authors recommend a co-development of culturally appropriate psychological intervention for persons with a history of self-harm and suicidal ideation to be tested in randomized control trials.

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