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Discovering widespread microbial processes that drive unexpected variation in carbon cycling may improve modeling and management of soil carbon (Prescott, 2010; Wieder et al., 2015a, 2018). A first step is to identify community features linked to carbon cycle variation. We addressed this challenge using an epidemiological approach with 206 soil communities decomposing Ponderosa pine litter in 618 microcosms. Carbon flow from litter decomposition was measured over a 6-week incubation. Cumulative CO2 from microbial respiration varied two-fold among microcosms and dissolved organic carbon (DOC) from litter decomposition varied five-fold, demonstrating large functional variation despite constant environmental conditions where strong selection is expected. To investigate microbial features driving DOC concentration, two microbial community cohorts were delineated as "high" and "low" DOC. For each cohort, communities from the original soils and from the final microcosm communities after the 6-week incubation with litter were taxonomically profiled. A logistic model including total biomass, fungal richness, and bacterial richness measured in the original soils or in the final microcosm communities predicted the DOC cohort with 72 (P < 0.05) and 80 (P < 0.001) percent accuracy, respectively. The strongest predictors of the DOC cohort were biomass and either fungal richness (in the original soils) or bacterial richness (in the final microcosm communities). Successful forecasting of functional patterns after lengthy community succession in a new environment reveals strong historical contingencies. Forecasting future community function is a key advance beyond correlation of functional variance with end-state community features. The importance of taxon richness-the same feature linked to carbon fate in gut microbiome studies-underscores the need for increased understanding of biotic mechanisms that can shape richness in microbial communities independent of physicochemical conditions.
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Experiments were conducted to determine the relative bioavailability (RBV) of the calcium salt of the hydroxy analog of dl-methionine (MHA-Ca, 84%) to dl-methionine (dl-Met, 99%) as Met sources fed to pigs. In experiment 1, 42 crossbred barrows (initial BW of 15.0 ± 0.7 kg) were allotted to 7 treatments in an N-balance study. The basal diet (BD) was formulated to contain 15.4% CP and 0.22% Met (70% of requirement). Diets included (1) BD, (2) BD + 0.025% dl-Met, (3) BD + 0.050% dl-Met, (4) BD + 0.075% dl-Met, (5) BD + 0.038% MHA-Ca, (6) BD + 0.077% MHA-Ca, and (7) BD + 0.115% MHA-Ca. An increase in dietary inclusion rates of both Met sources linearly increased (P < 0.01) N retained (g/d) and N retention (% of intake). Using linear slope-ratio regression, the RBV value of MHA-Ca to dl-Met for N retained (g/d) was 63.0% on a product-to-product basis (75.0% on an equimolar basis). In experiment 2, 40 crossbred barrows (initial BW of 15.5 ± 1.5 kg) were allotted to 5 treatments in another N-balance study. The BD was formulated to contain 17.0% CP and 0.22% Met (70% of requirement). Diets included (1) BD, (2) BD + 0.030% dl-Met, (3) BD + 0.060% dl-Met, (4) BD + 0.046% MHA-Ca, and (5) BD + 0.092% MHA-Ca. Increasing levels of dl-Met or MHA-Ca increased N retained (g/d) and N retention (% of intake) linearly (P < 0.001) and quadratically (P < 0.05). Using linear slope-ratio regression, a product-to-product RBV value of MHA-Ca to dl-Met was 68.4% (81.4% on an equimolar basis) for N retained (g/d). In experiment 3, 276 pigs (12 barrow and 11 gilt replicates; initial BW of 7.09 ± 1.1 kg) were used in 3 diet preference studies. Pigs were randomly allotted to 1 of 3 treatment comparisons of feed choice: (1) BD (0.23% Met) or BD + 0.07% dl-Met; (2) BD or BD + 0.0825% MHA-Ca, and (3) BD + 0.07% dl-Met or BD + 0.0825% MHA-Ca. Pigs consumed a higher percentage (55 vs. 45%; P = 0.008) of their total feed intake from the diet supplemented with 0.07% dl-Met in Comparison 1, but a lower percentage (45 vs. 55%; P = 0.003) of their total feed intake from the diet supplemented with 0.0825% MHA-Ca in Comparison 2. There was no diet preference for dl-Met or MHA-Ca in Comparison 3. The observed Met source preference differences occurred in the barrow replicates but not in the gilt replicates. These results demonstrated the mean RBV of MHA-Ca to dl-Met of 65.7% on a product-to-product (wt/wt) basis or 78.2% on an equimolar basis and that a preference for Met sources was observed in barrows but not in gilts.
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Ração Animal , Cálcio , Ração Animal/análise , Animais , Disponibilidade Biológica , Dieta/veterinária , Feminino , Metionina/análogos & derivados , Metionina/metabolismo , Nitrogênio , SuínosRESUMO
The high loss rate of forest ecosystem by deforestation in the Trans-Mexican Volcanic Belt is one of the principal ecological problems of central Mexico, even in natural protected areas. We compiled a checklist and determined ß-diversity indexes of amphibians and reptiles of the highly disturbed protected area, La Malinche National Park (LMNP) in Mexico, to determine the principal habitats for herpetofaunal conservation. After our extensive eight-year field sampling, we documented 28 species (nine amphibians and 19 reptiles), representing 11 families and 18 genera; four of these species are new records for LMNP. Of the species, 89% are endemic to Mexico. The IUCN Red List considers 22 species as Least Concern, one as Near Threatened, and four as Vulnerable. Meanwhile, the Environmental Viability Scores categorize three species as low vulnerability, 15 as medium, and 10 as high. According to the Mexican list of protected species, eight species are under Special Protection and nine are considered Vulnerable. The dissimilarity index between habitat types (ßsør) in both groups is high, principally due to the environmental gradient generated by the altitudinal range. Abies and Pine forest are high diversity areas for amphibians and reptiles, respectively, and must be considered for special protection. LMNP hosts more than 60% of the herpetofauna of Tlaxcala and is the principal "conservation island" for this state. Therefore, based on the percentage of state species represented, endemism and the current social and ecological problems, additional efforts that involve the local communities to protect the biodiversity of this National Park are necessary.
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El patrón llamado 'crazy paving' en tomografia computada de tórax (TAC) puede deberse a diferentes condiciones siendo una de ellas la Proteinosis Alveolar Pulmonar (PAP), rara condición que puede llevar a insuficiencia respiratoria y a menudo, a la muerte. Presentamos el caso de una mujer joven con una historia de un año de evolución de disnea progresiva y tos seca que consultó por un cuadro de aparición brusca de fiebre, calofríos, malestar general y falla respiratoria hipoxémica severa (PaO2 = 51,9 mmHg con FiO2 = 0,50) en la cual la TAC de tórax mostraba un patrón de empedrado o 'crazy paving' que significó un desafío diagnóstico resuelto finalmente con una biopsia pulmonar quirúrgica que mostró una PAP. Ante el fracaso del tratamiento tradicional de Lavado Pulmonar Total (LPT) se usó una aproximación terapéutica novedosa consistente en una serie de 4 lavados lobares con un perfluorocarbono, Perflubron (PFC) bajo anestesia local seguido por 5 sesiones de Plasmaféresis. Casi inmediatamente después de este tratamiento la paciente evidenció mejoría radiológica y funcional. La PaO2 fue de 89,9 mmHg respirando aire ambiental y la CVF y el VEF1 aumentaron alcanzado respectivamente el 77 y el 75% de sus valores normales de referencia. Dadas las características químicas y físicas del PFC, pensamos que es una alternativa válida al LPT en estos casos.
Crazy paving computed tomography pattern may be due to a number of causes, one of them being Pulmonary Alveolar Proteinosis, a rare condition leading to respiratory failure and often to death. We present the case of a young woman with a one-year history of progressive dyspnea and dry cough, who consulted for an acute onset of fever, chills, malaise and severe hypoxemic respiratory failure (PaO2 = 51.9 mmHg; FiO2 = 0.50) with a 'crazy paving' pattern on chest CT. This diagnostic challenge was resolved by a surgical lung biopsy that showed a pulmonary alveolar proteinosis. Taking into account that the traditional treatment using whole lung lavage had already failed in this patient, a novel therapeutic approach was settled. A series of 4 lobar lavages with a perfluorocarbon (Perflubron) under local anesthesia followed by 5 plasmapheresis sessions were carried out. The patient showed radiographic and functional improvement almost immediately after this treatment. PaO2 was 89.9 mmHg breathing room air and FVC and FEV1 increased to reach 77 and 75% respectively of their normal reference values. Because of its chemical and physical properties we think this novel therapeutic approach should be a valuable alternative to saline solution for whole lung lavage in these cases.
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Humanos , Feminino , Adulto , Proteinose Alveolar Pulmonar/terapia , Proteinose Alveolar Pulmonar/diagnóstico por imagem , Proteinose Alveolar Pulmonar/cirurgia , Proteinose Alveolar Pulmonar/complicações , Insuficiência Respiratória/prevenção & controle , Tomografia Computadorizada por Raios X/métodos , Plasmaferese , Lavagem Broncoalveolar/métodos , FluorocarbonosRESUMO
Platinum drugs are the frontline therapy in many carcinomas, including high-grade serous ovarian cancers. Clinically, high-grade serous carcinomas have an apparent complete response to carboplatin, but tumors invariably recur and response to platinum drugs diminishes over time. Standard of care prohibits re-administration of platinum drugs to these patients who are labeled as having platinum-resistant disease. In this stage patients are treated with non-platinum agents and outcomes are often poor. In vivo and in vitro data presented here demonstrate that this clinical dogma should be challenged. Platinum drugs can be an effective therapy even for platinum-resistant carcinomas as long as they are combined with an agent that specifically targets mechanisms of platinum resistance exploited by the therapy-resistant tumor subpopulations. High levels of cellular inhibitor of apoptosis proteins cIAP1 and 2 (cIAP) were detected in up to 50% of high-grade serous and non-high-grade serous platinum-resistant carcinomas. cIAP proteins can induce platinum resistance and they are effectively degraded with the drug birinapant. In platinum-resistant tumors with ≥22.4 ng of cIAP per 20 µg of tumor lysate, the combination of birinapant with carboplatin was effective in eliminating the cancer. Our findings provide a new personalized therapeutic option for patients with platinum-resistant carcinomas. The efficacy of birinapant in combination with carboplatin should be tested in high-grade serous carcinoma patients in a clinical trial.
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BACKGROUND AND OBJECTIVES: Host- and bacteria-derived proteinases are considered to play critical roles in periodontitis progression. This study investigated the ability of a blackcurrant extract and its major anthocyanins (cyanidin-3-O-glucoside, cyanidin-3-O-rutinoside and delphinidin-3-O-rutinoside) to inhibit the activity of matrix metalloproteinases (MMPs), neutrophil elastase and periodontopathogen (Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola) proteinases. MATERIAL AND METHODS: Enzyme inhibition was detected using fluorometric and colorimetric assays after incubating blackcurrant extract and its major anthocyanins (at concentrations of 6.25, 12.5, 25 and 50 µg/mL) with MMPs, elastase or bacterial proteinases, along with their specific substrates. Substrate degradation was recorded every hour for up to 4 h. RESULTS: The blackcurrant extract (50 µg/mL) inhibited all proteinases tested. MMP-1 and MMP-9 were significantly inhibited by pure anthocyanins at concentrations ranging from 6.25 to 50 µg/mL. Elastase activity was inhibited by cyanidin-3-O-glucoside and cyanidin-3-O-rutinoside in the range of 6.25-50 µg/mL and by delphinidin-3-O-rutinoside at 50 µg/mL. P. gingivalis, T. forsythia and T. denticola proteinases were also significantly inhibited by pure anthocyanins. In all cases, enzyme inhibition was time-dependent. CONCLUSION: Our study showed that a blackcurrant extract and its major anthocyanins were able to inhibit the activity of host- and bacteria-derived proteinases. This suggests that such natural compounds may represent promising agents for use in adjunctive treatments for periodontitis.
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Antocianinas/farmacologia , Extratos Vegetais/farmacologia , Inibidores de Proteases/farmacologia , Ribes/química , Proteínas de Bactérias/antagonistas & inibidores , Bacteroides/enzimologia , Glucosídeos/farmacologia , Humanos , Elastase de Leucócito/efeitos adversos , Metaloproteinase 1 da Matriz/efeitos adversos , Inibidores de Metaloproteinases de Matriz , Porphyromonas gingivalis/enzimologia , Proteólise , Treponema denticola/enzimologiaRESUMO
La rabia representa un importante problema de salud pública en el estado Zulia, constituyendo en Venezuela la entidad con mayor incidencia de casos en animales y humanos, registrándose 25 muertes humanas por rabia durante el período enero 1993 - junio 2009. Describir su comportamiento epidemiológico durante este período constituye nuestro objetivo. Estudio epidemiológico realizado: observacional, descriptivo. La muestra incluyó todos los casos confirmados como rabia humana en la entidad durante este lapso (n = 25), con edades entre 2-57 años, de ambos sexos y procedentes de 7 municipios con incidencia. Datos tomados de los informes de casos de rabia de la Dirección Regional de Epidemiología. Los resultados están expresados en porcentajes, promedios, intervalos de confianza, tasa de letalidad y distribuciones según edad, sexo y municipio de ocurrencia. La mayor incidencia ocurrió en varones (68%). El grupo entre 2-10 años resultó mayormente afectado (60%). El 80% casos no efectuó consulta post exposición no recibiendo inmunoprofilaxia oportuna. La Inmunofluorescencia directa fue utilizada para confirmación diagnóstica. El conocimiento sobre las formas de transmisión de rabia es crucial para prevenirla; el tiempo entre la inoculación viral y la invasión neural es quizá el único período para una inmunoprofilaxia efectiva
Rabies represents a major public health problem in the State of Zulia, constituting the entitywith the highest incidence of animal and human cases in Venezuela, registering 25 human deathsby rabies from January, 1993 June, 2009. The objective of this study is to describe its epidemiologicalbehavior during this period; the epidemiological study was observational and descriptive.The sample included all cases confirmed as human rabies in the entity during this period (n = 25);they were between 2 and 57 years of age, from both sexes and 7 municipalities. Data was takenfrom the reports of rabies cases in the Regional Epidemiology Direction. The results are expressedin percentages, means, confidence intervals, mortality rate and distributions according to age, sexand municipality of occurrence. The highest incidence was in males (68%).The group between2-10 years was principally affected (60%). Eighty per cent of the cases did not seek post-exposureconsultation and did not receive timely prophylaxis. The direct fluorescent antibody test was usedfor diagnostic confirmation. Knowledge about forms of rabies transmission is crucial for its prevention;the time between viral inoculation and neural invasion is perhaps the only period for aneffective prophylaxis
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Humanos , Masculino , Adolescente , Adulto , Feminino , Criança , Raiva/diagnóstico , Raiva/epidemiologia , Raiva/mortalidade , Saúde PúblicaRESUMO
Matrix metalloproteinases (MMPs) produced by resident and inflammatory cells in response to periodontopathogens play a major role in periodontal tissue destruction. Our aim was to investigate the effects of A-type cranberry proanthocyanidins (AC-PACs) on: (i) the production of various MMPs by human monocyte-derived macrophages stimulated with Aggregatibacter actinomycetemcomitans lipopolysaccharide (LPS), and (ii) the catalytic activity of recombinant MMP-1 and MMP-9. The effects of AC-PACs on the expression of 5 protein kinases and the activity of nuclear factor-kappa B (NF-kappaB) p65 in macrophages stimulated with LPS were also monitored. Our results indicated that AC-PACs inhibited the production of MMPs in a concentration-dependent manner. Furthermore, the catalytic activity of MMP-1 and MMP-9 was also inhibited. The inhibition of MMP production was associated with reduced phosphorylation of key intracellular kinases and the inhibition of NF-kappaB p65 activity. AC-PACs thus show potential for the development of novel host-modulating strategies to inhibit MMP-mediated tissue destruction during periodontitis.
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Inibidores de Metaloproteinases de Matriz , Periodontite/enzimologia , Extratos Vegetais/farmacologia , Proantocianidinas/farmacologia , Aggregatibacter actinomycetemcomitans , Relação Dose-Resposta a Droga , Humanos , Lipopolissacarídeos , Macrófagos/enzimologia , Metaloproteinases da Matriz/metabolismo , NF-kappa B/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Proteínas Quinases/biossíntese , Proteínas Recombinantes/metabolismo , Vaccinium macrocarponRESUMO
BACKGROUND AND OBJECTIVE: Naringenin, a naturally occurring flavonoid, possesses a wide range of pharmacological properties. The purpose of this study was to investigate the effect of naringenin on human osteoclastogenesis and osteoclastic bone resorption. MATERIAL AND METHODS: Naringenin was tested in a human osteoclastogenesis model using primary osteoclast precursor cells activated by receptor activator of nuclear factor-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) for 6 days. Osteoclastogenesis was assessed by determining the number of tartrate-resistant acid phosphatase (TRAP)-stained multinuclear cells, while the secretion of factors involved in osteoclastogenesis was assessed using enzyme-linked immunosorbent assays. The effect of naringenin on bone resorption was investigated using an OsteoAssay human bone plate coupled with an immunoassay to evaluate the release of helical peptide 620-633 from the alpha1 chain of type I collagen. RESULTS: Naringenin was non-toxic at the highest concentration used (50 microg/ml). Naringenin (10, 25 and 50 microg/ml) significantly inhibited osteoclastogenesis (by 29 +/- 5, 57 +/- 8 and 96 +/- 1%, respectively). Naringenin also markedly inhibited the secretion of interleukin (IL)-1alpha (by 59%), IL-23 (by 87%) and monocyte chemoattractant protein-1 (by 58%). Lastly, naringenin (10, 25 and 50 microg/ml) significantly decreased the release of helical peptide 620-633, an indicator of bone resorption activity (by 44 +/- 0.5, 73 +/- 0.5 and 86 +/- 1%, respectively). CONCLUSIONS: Naringenin can inhibit human osteoclastogenesis and osteoclastic bone resorption. It thus holds promise as a therapeutic or preventive agent for bone-related diseases such as periodontitis.
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Conservadores da Densidade Óssea/farmacologia , Reabsorção Óssea/tratamento farmacológico , Flavanonas/farmacologia , Osteoclastos/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Quimiocina CCL2/antagonistas & inibidores , Flavanonas/uso terapêutico , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Interleucina-1alfa/antagonistas & inibidores , Interleucina-23/antagonistas & inibidores , Fator Estimulador de Colônias de Macrófagos/metabolismo , Ligante RANK/metabolismoRESUMO
BACKGROUND AND OBJECTIVE: Periodontitis is a chronic inflammatory disease of bacterial etiology, affecting tooth-supporting tissues. The host inflammatory response to periodontopathogens, notably the high and continuous production of cytokines, is considered a major factor causing the local tissue destruction observed in periodontitis. The aim of the present study was to investigate the effect of naringenin, a major flavanone in grapefruits and tomatoes, on the lipopolysaccharide-induced pro-inflammatory cytokine production by host cells, using two different models. MATERIAL AND METHODS: The effect of naringenin was characterized using macrophages stimulated with the lipopolysaccharide of either Aggregatibacter actinomycetemcomitans or Escherichia coli and using whole blood stimulated with A. actinomycetemcomitans lipopolysaccharide, in the presence or absence of naringenin. Lipopolysaccharide-induced interleukin-1 beta, interleukin-6, interleukin-8 and tumor necrosis factor-alpha production by macrophages and whole-blood samples treated with naringenin were evaluated using an enzyme-linked immunosorbent assay. Changes in the phosphorylation states of macrophage kinases induced by A. actinomycetemcomitans lipopolysaccharide and naringenin were characterized by immunoblot screening. RESULTS: Our results clearly indicated that naringenin is a potent inhibitor of the pro-inflammatory cytokine response induced by lipopolysaccharide in both macrophages and in whole blood. Naringenin markedly inhibited the phosphorylation on serines 63 and 73 of Jun proto-oncogene-encoded AP-1 transcription factor in lipopolysaccharide-stimulated macrophages. CONCLUSION: The results from the present study suggest that naringenin holds promise as a therapeutic agent for treating inflammatory diseases such as periodontitis.
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Anti-Inflamatórios/farmacologia , Flavanonas/farmacologia , Macrófagos/efeitos dos fármacos , Periodontite/sangue , Aggregatibacter actinomycetemcomitans , Escherichia coli , Humanos , Mediadores da Inflamação/antagonistas & inibidores , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/efeitos dos fármacos , Interleucina-6/antagonistas & inibidores , Interleucina-8/antagonistas & inibidores , Interleucina-8/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Macrófagos/enzimologia , Fosforilação/efeitos dos fármacos , Fosfotransferases/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-jun/antagonistas & inibidores , Serina/antagonistas & inibidores , Fator de Transcrição AP-1/antagonistas & inibidores , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Células U937 , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidoresRESUMO
This paper presents an iterative method based on the minimal residual algorithm for tomographic attenuation compensated reconstruction from attenuated cone-beam projections given the attenuation distribution. Unlike conjugate-gradient based reconstruction techniques, the proposed minimal residual based algorithm solves directly a quasisymmetric linear system, which is a preconditioned system. Thus it avoids the use of normal equations, which improves the convergence rate. Two main contributions are introduced. First, a regularization method is derived for quasisymmetric problems, based on a Tikhonov-Phillips regularization applied to the factorization of the symmetric part of the system matrix. This regularization is made spatially adaptive to avoid smoothing the region of interest. Second, our existing reconstruction algorithm for attenuation correction in parallel-beam geometry is extended to cone-beam geometry. A circular orbit is considered. Two preconditioning operators are proposed: the first one is Grangeat's inversion formula and the second one is Feldkamp's inversion formula. Experimental results obtained on simulated data are presented and the shadow zone effect on attenuated data is illustrated.