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Carbon and other volatiles in the form of gases, fluids or mineral phases are transported from Earth's surface into the mantle at convergent margins, where the oceanic crust subducts beneath the continental crust. The efficiency of this transfer has profound implications for the nature and scale of geochemical heterogeneities in Earth's deep mantle and shallow crustal reservoirs, as well as Earth's oxidation state. However, the proportions of volatiles released from the forearc and backarc are not well constrained compared to fluxes from the volcanic arc front. Here we use helium and carbon isotope data from deeply sourced springs along two cross-arc transects to show that about 91 per cent of carbon released from the slab and mantle beneath the Costa Rican forearc is sequestered within the crust by calcite deposition. Around an additional three per cent is incorporated into the biomass through microbial chemolithoautotrophy, whereby microbes assimilate inorganic carbon into biomass. We estimate that between 1.2 × 108 and 1.3 × 1010 moles of carbon dioxide per year are released from the slab beneath the forearc, and thus up to about 19 per cent less carbon is being transferred into Earth's deep mantle than previously estimated.
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Dióxido de Carbono/análise , Sequestro de Carbono , Sedimentos Geológicos/química , Biomassa , Isótopos de Carbono , Costa Rica , Sedimentos Geológicos/microbiologia , HélioRESUMO
Change history: In this Article, the original affiliation 2 was not applicable and has been removed. In addition, in the Acknowledgements there was a statement missing and an error in a name. These errors have been corrected online.
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An Amendment to this paper has been published and can be accessed via a link at the top of the paper.
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OBJECTIVE: To develop sets of core and optional recommended domains for describing and evaluating Osteoarthritis Management Programs (OAMPs), with a focus on hip and knee Osteoarthritis (OA). DESIGN: We conducted a 3-round modified Delphi survey involving an international group of researchers, health professionals, health administrators and people with OA. In Round 1, participants ranked the importance of 75 outcome and descriptive domains in five categories: patient impacts, implementation outcomes, and characteristics of the OAMP and its participants and clinicians. Domains ranked as "important" or "essential" by ≥80% of participants were retained, and participants could suggest additional domains. In Round 2, participants rated their level of agreement that each domain was essential for evaluating OAMPs: 0 = strongly disagree to 10 = strongly agree. A domain was retained if ≥80% rated it ≥6. In Round 3, participants rated remaining domains using same scale as in Round 2; a domain was recommended as "core" if ≥80% of participants rated it ≥9 and as "optional" if ≥80% rated it ≥7. RESULTS: A total of 178 individuals from 26 countries participated; 85 completed all survey rounds. Only one domain, "ability to participate in daily activities", met criteria for a core domain; 25 domains met criteria for an optional recommendation: 8 Patient Impacts, 5 Implementation Outcomes, 5 Participant Characteristics, 3 OAMP Characteristics and 4 Clinician Characteristics. CONCLUSION: The ability of patients with OA to participate in daily activities should be evaluated in all OAMPs. Teams evaluating OAMPs should consider including domains from the optional recommended set, with representation from all five categories and based on stakeholder priorities in their local context.
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Osteoartrite do Quadril , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/terapia , Osteoartrite do Quadril/terapia , Consenso , Pessoal de Saúde , Inquéritos e Questionários , Técnica DelphiRESUMO
BACKGROUND: Orofacial clefts (OFCs) are common birth defects with complex etiology. Genome wide association studies for OFC have identified SNPs in and near MAFB. MAFB is a transcription factor critical for structural development of digits, kidneys, skin, and brain. MAFB is also expressed in the craniofacial region. Previous sequencing of MAFB in a Filipino population revealed a novel missense variant significantly associated with an increased risk for OFC. This MAFB variant, leading to the amino acid change H131Q, was knocked into the mouse Mafb, resulting in the MafbH131Q allele. The MafbH131Q construct was engineered to allow for deletion of Mafb ("Mafbdel "). RESULTS: Mafbdel/del animals died shortly after birth. Conversely, MafbH131Q/H131Q mice survived into adulthood at Mendelian ratios. Mafbdel/del and MafbH131Q/H131Q heads exhibited normal macroscopic and histological appearance at all embryonic time points evaluated. The periderm was intact based on expression of keratin 6, p63, and E-cadherin. Despite no effect on craniofacial morphogenesis, H131Q inhibited the Mafb-dependent promoter activation of Arhgap29 in palatal mesenchymal, but not ectodermal-derived epithelial cells in a luciferase assay. CONCLUSIONS: Mafb is dispensable for murine palatogenesis in vivo, and the cleft-associated variant H131Q, despite its lack of morphogenic effect, altered the expression of Arhgap29 in a cell-dependent context.
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Fissura Palatina/metabolismo , Fator de Transcrição MafB/metabolismo , Palato/metabolismo , Polimorfismo de Nucleotídeo Único , Alelos , Animais , Fissura Palatina/genética , Predisposição Genética para Doença , Fator de Transcrição MafB/genética , Camundongos , Camundongos Transgênicos , Palato/embriologiaRESUMO
Cultured Myxococcota are predominantly aerobic soil inhabitants, characterized by their highly coordinated predation and cellular differentiation capacities. Little is currently known regarding yet-uncultured Myxococcota from anaerobic, nonsoil habitats. We analyzed genomes representing one novel order (o__JAFGXQ01) and one novel family (f__JAFGIB01) in the Myxococcota from an anoxic freshwater spring (Zodletone Spring) in Oklahoma, USA. Compared to their soil counterparts, anaerobic Myxococcota possess smaller genomes and a smaller number of genes encoding biosynthetic gene clusters (BGCs), peptidases, one- and two-component signal transduction systems, and transcriptional regulators. Detailed analysis of 13 distinct pathways/processes crucial to predation and cellular differentiation revealed severely curtailed machineries, with the notable absence of homologs for key transcription factors (e.g., FruA and MrpC), outer membrane exchange receptor (TraA), and the majority of sporulation-specific and A-motility-specific genes. Further, machine learning approaches based on a set of 634 genes informative of social lifestyle predicted a nonsocial behavior for Zodletone Myxococcota. Metabolically, Zodletone Myxococcota genomes lacked aerobic respiratory capacities but carried genes suggestive of fermentation, dissimilatory nitrite reduction, and dissimilatory sulfate-reduction (in f_JAFGIB01) for energy acquisition. We propose that predation and cellular differentiation represent a niche adaptation strategy that evolved circa 500 million years ago (Mya) in response to the rise of soil as a distinct habitat on Earth. IMPORTANCE The phylum Myxococcota is a phylogenetically coherent bacterial lineage that exhibits unique social traits. Cultured Myxococcota are predominantly aerobic soil-dwelling microorganisms that are capable of predation and fruiting body formation. However, multiple yet-uncultured lineages within the Myxococcota have been encountered in a wide range of nonsoil, predominantly anaerobic habitats, and the metabolic capabilities, physiological preferences, and capacity of social behavior of such lineages remain unclear. Here, we analyzed genomes recovered from a metagenomic analysis of an anoxic freshwater spring in Oklahoma, USA, that represent novel, yet-uncultured, orders and families in the Myxococcota. The genomes appear to lack the characteristic hallmarks for social behavior encountered in Myxococcota genomes and displayed a significantly smaller genome size and a smaller number of genes encoding biosynthetic gene clusters, peptidases, signal transduction systems, and transcriptional regulators. Such perceived lack of social capacity was confirmed through detailed comparative genomic analysis of 13 pathways associated with Myxococcota social behavior, as well as the implementation of machine learning approaches to predict social behavior based on genome composition. Metabolically, these novel Myxococcota are predicted to be strict anaerobes, utilizing fermentation, nitrate reduction, and dissimilarity sulfate reduction for energy acquisition. Our results highlight the broad patterns of metabolic diversity within the yet-uncultured Myxococcota and suggest that the evolution of predation and fruiting body formation in the Myxococcota has occurred in response to soil formation as a distinct habitat on Earth.
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Bactérias/citologia , Genoma Bacteriano , Nascentes Naturais/microbiologia , Bactérias/genética , Nitritos , Oklahoma , Peptídeo Hidrolases , Transdução de Sinais , Solo , Sulfatos , Microbiologia da ÁguaRESUMO
Psoriasis (PS) is a common inflammatory and incurable skin disease affecting 2-3% of the human population. Although genome-wide association studies implicate more than 60 loci, the full complement of genetic factors leading to disease is not known. Rare, highly penetrant, gain-of-function, dominantly acting mutations within the human caspase recruitment domain family, member 14 (CARD14) gene lead to the development of PS and psoriatic arthritis (PSA) (a familial p.G117S and de-novo p.E138A alteration). These residues are conserved in mouse and orthologous Knock-In (KI) mutations within Card14 were created. The Card14tm.1.1Sun allele (G117S) resulted in no clinically or histologically evident phenotype of the skin or joints in young adult or old mice. However, mice carrying the Card14tm2.1Sun mutant allele (E138A) were runted and developed thick, white, scaly skin soon after birth, dying within two weeks or less. The skin hyperplasia and inflammation was remarkable similarity to human PS at the clinical, histological, and transcriptomic levels. For example, the skin was markedly acanthotic and exhibited orthokeratotic hyperkeratosis with minimal inflammation and no pustules and transcripts affecting critical pathways of epidermal differentiation and components of the IL17 axis (IL23, IL17A, IL17C, TNF and IL22) were altered. Similar changes were seen in a set of orthologous microRNAs previously associated with PS suggesting conservation across species. Crossing the Card14tm2.1Sun/WT mice to C57BL/6NJ, FVB/NJ, CBA/J, C3H/HeJ, and 129S1/SvImJ generated progeny with epidermal acanthosis and marked orthokeratotic hyperkeratosis regardless of the hybrid strain. Of these hybrid lines, only the FVB;B6N(129S4) mice survived to 250â¯days of age or older and has led to recombinant inbred lines homozygous for Card14E138A that are fecund and have scaly skin disease. This implicates that modifiers of PS severity exist in mice, as in the familial forms of the disease in humans.
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Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/fisiologia , Mutação com Ganho de Função , Genes Modificadores , Guanilato Ciclase/genética , Guanilato Quinases/fisiologia , Inflamação/genética , Proteínas de Membrana/genética , Psoríase/genética , Dermatopatias/genética , Animais , Feminino , Técnicas de Introdução de Genes , Humanos , Inflamação/patologia , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Camundongos Knockout , Psoríase/patologia , Índice de Gravidade de Doença , Dermatopatias/patologia , TranscriptomaRESUMO
Spontaneously arising mouse mutations have served as the foundation for understanding gene function for more than 100 years. We have used exome sequencing in an effort to identify the causative mutations for 172 distinct, spontaneously arising mouse models of Mendelian disorders, including a broad range of clinically relevant phenotypes. To analyze the resulting data, we developed an analytics pipeline that is optimized for mouse exome data and a variation database that allows for reproducible, user-defined data mining as well as nomination of mutation candidates through knowledge-based integration of sample and variant data. Using these new tools, putative pathogenic mutations were identified for 91 (53%) of the strains in our study. Despite the increased power offered by potentially unlimited pedigrees and controlled breeding, about half of our exome cases remained unsolved. Using a combination of manual analyses of exome alignments and whole-genome sequencing, we provide evidence that a large fraction of unsolved exome cases have underlying structural mutations. This result directly informs efforts to investigate the similar proportion of apparently Mendelian human phenotypes that are recalcitrant to exome sequencing.
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Exoma , Mutação , Animais , Feminino , Doenças Genéticas Inatas/genética , Ligação Genética , Variação Genética , Estudo de Associação Genômica Ampla , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Masculino , Camundongos , Fenótipo , Reprodutibilidade dos TestesRESUMO
Mus pahari is a wild-derived, inbred mouse strain. M. pahari colony managers observed fragility of this strain's skin resulting in separation of tail skin from the mouse if handled incorrectly. Tail skin tension testing of M. pahari resulted in significantly lowered force threshold for caudal skin rupture and loss in comparison to closely related inbred mouse species and subspecies and even more than a model for junctional epidermolysis bullosa. Histologically, the tail skin separated at the subdermal level with the dermis firmly attached to the epidermis, excluding the epidermolysis bullosa complex of diseases. The dermal collagen bundles were abnormally thickened and branched. Elastin fiber deposition was focally altered in the dermis adjacent to the hair follicle. Collagens present in the skin could not be differentiated between the species in protein gels following digestion with pepsin. Together these data suggest that M. pahari have altered extracellular matrix development resulting in separation of the skin below the level of the dermis with moderate force similar to the African spiny mouse (Acomys spp.).
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Pele/metabolismo , Pele/fisiopatologia , Cauda , Animais , Colágeno/metabolismo , Derme/metabolismo , Derme/patologia , Derme/fisiopatologia , Elasticidade , Elastina/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Pele/patologia , Especificidade da EspécieRESUMO
Mouse models of various types of inflammatory skin disease are often accompanied by increased dermal angiogenesis. The C3H/HeJ inbred strain spontaneously develops alopecia areata (AA), a cell mediated autoimmune disorder that can be controllably expanded using full thickness skin grafts to young unaffected mice. This provides a reproducible and progressive model for AA in which the vascularization of the skin can be examined. Mice receiving skin grafts from AA or normal mice were evaluated at 5, 10, 15, and 20 weeks after engraftment. Lymphatics are often overlooked as they are small slit-like structures above the hair follicle that resemble artifact-like separation of collagen bundles with some fixatives. Lymphatics are easily detected using lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1) by immunohistochemistry to label their endothelial cells. Using LYVE1, there were no changes in distribution or numbers of lymphatics although they were more prominent (dilated) in the mice with AA. Lyve1 transcripts were not significantly upregulated except at 10 weeks after skin grafting when clinical signs of AA first become apparent. Other genes involved with vascular growth and dilation or movement of immune cells were dysregulated, mostly upregulated. These findings emphasize aspects of AA not commonly considered and provide potential targets for therapeutic intervention.
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Alopecia em Áreas/patologia , Modelos Animais de Doenças , Sistema Linfático/patologia , Pele/patologia , Alopecia em Áreas/genética , Alopecia em Áreas/metabolismo , Animais , Perfilação da Expressão Gênica/métodos , Glicoproteínas/genética , Glicoproteínas/metabolismo , Folículo Piloso/irrigação sanguínea , Folículo Piloso/metabolismo , Folículo Piloso/patologia , Imuno-Histoquímica , Sistema Linfático/metabolismo , Vasos Linfáticos/metabolismo , Vasos Linfáticos/patologia , Proteínas de Membrana Transportadoras , Camundongos Endogâmicos C3H , Análise de Sequência com Séries de Oligonucleotídeos , Pele/irrigação sanguínea , Pele/metabolismo , Transplante de Pele/métodos , Fatores de TempoRESUMO
Technology now exists for rapid screening of mutated laboratory mice to identify phenotypes associated with specific genetic mutations. Large repositories exist for spontaneous mutants and those induced by chemical mutagenesis, many of which have never been fully studied or comprehensively evaluated. To supplement these resources, a variety of techniques have been consolidated in an international effort to create mutations in all known protein coding genes in the mouse. With targeted embryonic stem cell lines now available for almost all protein coding genes and more recently CRISPR/Cas9 technology, large-scale efforts are underway to create further novel mutant mouse strains and to characterize their phenotypes. However, accurate diagnosis of skin, hair, and nail diseases still relies on careful gross and histological analysis, and while not automated to the level of the physiological phenotyping, histopathology still provides the most direct and accurate diagnosis and correlation with human diseases. As a result of these efforts, many new mouse dermatological disease models are being characterized and developed.
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Alopecia em Áreas/genética , Análise Mutacional de DNA , Modelos Animais de Doenças , Animais , Genoma , Humanos , Camundongos , Camundongos Knockout , FenótipoRESUMO
Studies of spontaneous mutations in mice have provided valuable disease models and important insights into the mechanisms of human disease. Ruffled (rul) is a new autosomal recessive mutation causing abnormal hair coat in mice. The rul allele arose spontaneously in the RB156Bnr/EiJ inbred mouse strain. In addition to an abnormal coat texture, we found diffuse epidermal blistering, abnormal electrocardiograms (ECGs), and ventricular fibrosis in mutant animals. Using high-throughput sequencing (HTS) we found a frameshift mutation at 38,288,978bp of chromosome 13 in the desmoplakin gene (Dsp). The predicted mutant protein is truncated at the c-terminus and missing the majority of the plakin repeat domain. The phenotypes found in Dsp(rul) mice closely model a rare human disorder, Carvajal-Huerta syndrome. Carvajal-Huerta syndrome (CHS) is a rare cardiocutaneous disorder that presents in humans with wooly hair, palmoplantar keratoderma and ventricular cardiomyopathy. CHS results from an autosomal recessive mutation on the 3' end of desmoplakin (DSP) truncating the full length protein. The Dsp(rul) mouse provides a new model to investigate the pathogenesis of CHS, as well as the underlying basic biology of the adhesion molecules coded by the desmosomal genes.
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Cardiomiopatias/genética , Desmoplaquinas/genética , Doenças do Cabelo/genética , Cabelo/patologia , Ceratodermia Palmar e Plantar/genética , Animais , Sequência de Bases , Cardiomiopatia Dilatada , Mutação da Fase de Leitura , Ligação Genética/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Dados de Sequência Molecular , Análise de Sequência de DNARESUMO
BACKGROUND: Healthcare-associated infections are prevalent in low- and middle-income countries and may be reduced through proper hand hygiene (HH) adherence during patient care. AIM: We produced and distributed alcohol-based hand rub (ABHR) to 19 public primary- and secondary-level healthcare facilities in Quetzaltenango, Guatemala, and carried out HH observations to assess healthcare workers' (HCWs) HH adherence, and to identify factors associated with this practice. HH adherence was defined as washing hands with soap and water or using ABHR. METHODS: Observations were conducted before (2021, baseline) and after (2022, follow-up) ABHR distribution to evaluate the evolution of HH practices over time. Bivariate comparisons and mixed-effects logistic regression models were used to explore associations between HH adherence and the following independent variables: healthcare facility level, type of contact performed, timing of HH performance, occupational category of HCW and materials present (e.g., water, soap, ABHR). FINDINGS: We observed 243 and 300 patient interactions among 67 and 82 HCWs at each time point, respectively. HH adherence was low for both observation periods (40% at baseline and 35% at follow-up). HCWs were more likely to adhere to HH during invasive contacts, after patient contact, and if the HCW was a physician. CONCLUSION: HH adherence varied by scenario, which underscores the importance of addressing multiple determinants of behaviour change to improve adherence. This requires interventions implemented with a multi-modal approach that includes both increasing access to HH materials and infrastructure, as well as HH education and training, monitoring and feedback, reminders, and promoting a HH safety culture.
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COVID-19 , Fidelidade a Diretrizes , Higiene das Mãos , Pessoal de Saúde , Humanos , Guatemala , COVID-19/prevenção & controle , Pessoal de Saúde/estatística & dados numéricos , Pessoal de Saúde/psicologia , Higiene das Mãos/estatística & dados numéricos , Higiene das Mãos/métodos , Higiene das Mãos/normas , Fidelidade a Diretrizes/estatística & dados numéricos , Feminino , Masculino , Desinfecção das Mãos/métodos , Infecção Hospitalar/prevenção & controle , Adulto , SARS-CoV-2 , Controle de Infecções/métodos , Instalações de Saúde/estatística & dados numéricosRESUMO
A number of single gene mutations in laboratory mice produce hair follicle defects resulting in deformed hair shafts. The radiation-induced (SB/LeJ-Foxq1(sa)) satin mutant mice have a satin-like sheen to their hair and dilute colouration. This sheen is due to failure of the hair shafts to develop normal medullas, while the pigment dilution is due to the unrelated beige (lysosomal trafficking regulator, Lyst(bg)) mutation. A new allelic mutation, Foxq1(sa-J), arose spontaneously on the albino (tyrosinase, Tyr(c)) MRL/MpJ-Fas(lpr) background. The Foxq1(sa-J) allele has a C to T transition at position 490. By contrast, the Foxq1(sa) mutant allele was confirmed to be a 67 base pair deletion followed by two base changes (GA to AT). Morphologic changes were similar to those seen in Hoxc13 transgenic and targeted mutant mice. This new allelic mutation provides yet another tool to investigate formation of the interior structures of hair shafts.
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Fatores de Transcrição Forkhead/genética , Cor de Cabelo/genética , Folículo Piloso/embriologia , Mutação/genética , Alelos , Sequência de Aminoácidos , Animais , Fatores de Transcrição Forkhead/análise , Camundongos , Camundongos Mutantes , Camundongos Transgênicos , Modelos Animais , Dados de Sequência Molecular , FenótipoRESUMO
Biogas production from municipal anaerobic digesters could potentially be boosted via co-digestion with organic wastes such as whey. The challenge is that whey production is seasonal. This research examined the effect of storing whey at ambient temperature on: (1) whey composition; (2) biogas production from co-digestion of the stored whey with municipal primary sludge. Whey storage resulted in acidification with formation of acetate, propionate and butyrate and a 9% reduction in total chemical oxygen demand (COD) over the 9-month trial. A control digester fed with primary sludge produced 0.18-0.23 m3 CH4/kgCOD(added). Co-digestion of fresh whey and sludge increased biogas production and the methane contribution from the whey was 0.29 m3CH4/kgCOD(added). When the fresh whey was substituted with stored whey, methane production by the whey remained at 0.29 m3CH4/kgCOD(added). The ability to store whey at ambient temperature and allow co-digestion year round will significantly improve the economics of biogas production from whey.
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Biocombustíveis/análise , Biocombustíveis/microbiologia , Proteínas do Leite/metabolismo , Esgotos/microbiologia , Anaerobiose , Biocombustíveis/economia , Reatores Biológicos/economia , Reatores Biológicos/microbiologia , Metano/análise , Metano/metabolismo , Proteínas do Leite/química , Estabilidade Proteica , Esgotos/química , Temperatura , Proteínas do Soro do LeiteRESUMO
Increasing biogas production from municipal anaerobic digesters via additional loading with industrial/agricultural wastes offers a low-cost, sustainable energy generation option of significant untapped potential. In this work, bench-top reactors were used to mimic a full-scale primary sludge digester operating at an organic loading rate (OLR) of 2.4 kg COD/m3 d and a 20 d hydraulic retention time (HRT). Co-digestion of whey with primary sludge was sustained at a loading rate of 3.2 kg COD/m3 d (17 d HRT) and boosted gas production to 151% compared to primary sludge digestion alone. Addition of chemical alkalinity enabled co-digestion of whey with primary sludge to be maintained at an elevated OLR of 6.4 kg COD/m3 d (11 d HRT) with gas production increased to 208%. However, when the chemical addition was simply replaced by cow manure, stable operation was maintained at OLRs of 5.2-6.9 kg COD/m3 d (11-14 d HRT) with gas production boosted up to 268%.
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Biocombustíveis/análise , Esterco/análise , Proteínas do Leite/química , Esgotos/análise , Animais , Bovinos , Proteínas do Soro do LeiteRESUMO
This comprehensive study analysed 55 articles published between 2011 and 2022 on the use of metal organic frameworks (MOFs) for phosphate adsorption. The study found that the performance of MOFs in phosphate adsorption is influenced by various factors such as the type of MOF, synthesis method, modification/alteration, and operational conditions (initial concentration, adsorbent dose, pH, contact time, and temperature). Most of the MOFs have a wide range of theoretical maximum adsorption capacity for phosphate, but their long-term use in phosphorus recovery may be limited due to the adsorption mechanisms being dominated by inner sphere complexation. The study employed machine learning to construct artificial neural network (ANN) models for predicting phosphate adsorption capacity based on input features from operation and synthesis procedures. The initial phosphate concentration was the most important input from the operational features, while the modulator agent was consistently relevant during MOF synthesis. The models showed strong fitting for most MOF types recorded for the study, such as UIO-66, MIL-100, ZIF-8, Al-MOFs, La-MOFs, and Ce-MOFs. Overall, this study provides valuable insights for the design of MOF adsorbents for phosphate adsorption and offers guidance for future research in this area.
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Estruturas Metalorgânicas , Fosfatos , Adsorção , Fósforo , Redes Neurais de ComputaçãoRESUMO
Numerous single gene mutations identified in humans and mice result in nail deformities with many similarities between the species. A spontaneous, autosomal, recessive mutation called witch nails (whnl) is described here where the distal nail matrix and nail bed undergo degenerative changes resulting in formation of an abnormal nail plate causing mice to develop long, curved nails. This mutation arose spontaneously in a colony of MRL/MpJ-Faslpr/J at The Jackson Laboratory. Homozygous mutant mice are recognizable by 8 weeks of age by their long, curved nails. The whnl mutation, mapped on Chromosome 15, is due to a 7-bp insertion identified in the 3' region of exon 9 in the Krt90 gene (formerly Riken cDNA 4732456N10Rik), and is predicted to result in a frameshift that changes serine 476 to arginine and subsequently introduces 36 novel amino acids into the protein before a premature stop codon (p. Ser476ArgfsTer36). By immunohistochemistry the normal KRT90 protein is expressed in the nail matrix and nail bed in control mice where lesions are located in mutant mice. Immunoreactivity toward equine KRT124, the ortholog of mouse KRT90, is restricted to the hoof lamellae (equine hoof wall and lamellae are homologous to the mouse nail plate and nail bed) and the mouse nail bed. Equine laminitis lesions are similar to those observed in this mutant mouse suggesting that the latter may be a useful model for hoof and nail diseases. This first spontaneous mouse mutation affecting the novel Krt90 gene provides new insight into the normal regulation of the molecular pathways of nail development.
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Doenças da Unha , Unhas Malformadas , Animais , Camundongos , Crescimento e Desenvolvimento , Cavalos , Mutação , Doenças da Unha/genética , Unhas/química , Unhas Malformadas/genéticaRESUMO
Active slag filters are an emerging technology for removing phosphorus (P) from wastewaters. Recent research revealed that adsorption onto Fe oxides/oxyhydroxides at near-neutral pH and oxidizing Eh is the key mechanism of P removal by melter slag filters. Currently, filter lifespan is limited by available adsorption sites. This study examined whether the performance and longevity of active filters could be improved via chemical treatment to create additional reactive sites as well as regenerate exhausted ones. Fresh original melter slag as well as slag from an exhausted full-scale filter was tested. Chemical reagents that could manipulate the pH/Eh of the slag granule surfaces and potentially activate them for further P removal were used, namely hydrochloric acid (HCI), sodium hydroxide (NaOH) and sodium dithionite (Na2S2O4). Waste stabilization pond effluent was then applied to the treated slag to assess the effectiveness of the treatments at improving P removal. Fresh slag treated with Na2S204 and HCl, respectively, retained 1.9 and 1.4 times more P from the effluent than the untreated fresh slag. These reagents were even more effective at regenerating the exhausted slag, increasing total retained P by a factor of 13 and six, respectively, compared with untreated slag. Sodium hydroxide was ineffective at increasing P removal. The higher P retention by the 'treated exhausted slag' compared with the 'treated fresh media' indicates that adsorption sites on melter slag filters become increasingly reactive with time. This research is the first study to provide evidence that P retention by active slag filters can be increased by both (1) chemical pre treatment and (2) chemical post-treatment once their P removal is exhausted, thereby potentially transforming them from a single use system to a more viable, reusable treatment technology.
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Filtração/instrumentação , Fósforo/química , Fósforo/isolamento & purificação , Desenho de Equipamento , Análise de Falha de Equipamento , Reutilização de EquipamentoRESUMO
Active filtration, where effluent is passed through a reactive substrate such as steel slag, offers a simple and cost-effective option for removing phosphorus (P) from effluent. This work summarises a series of studies that focused on the world's only full-scale active slag filter operated through to exhaustion. The filter achieved 75% P-removal during its first 5 years, reaching a retention capacity of 1.23 g P/kg slag but then its performance sharply declined. Scanning electron microscopy, X-ray diffraction, X-ray fluorescence, and chemical extractions revealed that P sequestration was primarily achieved via adsorption onto iron (Fe) oxyhydroxides on the slag's surface. It was concluded that batch equilibrium tests, whose use has been repeatedly proposed in the literature, cannot be used as an accurate predictor of filter adsorption capacity because Fe oxyhydroxides form via chemical weathering in the field, and laboratory tests don't account for this. Research into how chemical conditions affect slag's P retention capacity demonstrated that near-neutral pH and high redox are optimal for Fe oxyhydroxide stability and overall filter performance. However, as Fe oxyhydroxide sites fill up, removal capacity becomes exhausted. Attempts to regenerate P removal efficiency using physical techniques proved ineffective contrary to dogma in the literature. Based on the newly-developed understanding of the mechanisms of P removal, chemical regeneration techniques were investigated and were shown to strip large quantities of P from filter adsorption sites leading to a regenerated P removal efficiency. This raises the prospect of developing a breakthrough technology that can repeatedly remove and recover P from effluent.