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1.
Free Radic Biol Med ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38964592

RESUMO

Hyperglycaemia-induced oxidative stress plays significant roles in the development of type 2 diabetes and its complications. This study investigates effects of magainin-AM2 on high-sucrose diet induced redox imbalance and cognitive impairment in Drosophila melanogaster. Effects of various concentrations of sucrose, magainin-AM2 or a combination of both agents on mortality, eclosion rate, generation of reactive oxygen and nitrogen species, activities of antioxidant enzymes, thiol system, and markers of cognitive functions in control and treated flies were examined. Results showed that the exposure of flies to high sucrose (30% - 60% w/w) diet increased mortality rate (38 - 67%, P<0.001) and levels of glucose (1.8 - 1.9-fold, P<0.001), hydrogen peroxide (1.4 - 1.5-fold, P<0.01) and nitrite/nitrate (1.2-fold, P<0.01). Decreased levels of total thiol (53 - 59%, P<0.01), non-protein thiols (59 - 63%, P<0.01), catalase activities (39 - 47%, P<0.01 -0.05) and glutathione-s-transferase activities (31 - 43%, P<0.01 - 0.05) were also observed. Magainin-AM2 (0 - 10 µM/kg diet) did not affect fly mortality rate, levels of hydrogen peroxide and nitrite/nitrate, and activities of catalase and glutathione-s-transferase. However, the peptide produced a dose-dependent increase in total thiol 1.2 - 1.6-fold, P<0.001-0.01)and increases non-protein thiol levels at 10µM/kg diet (2.0-fold, P<0.01). Magainin-AM2 inhibited sucrose-induced elevation of glucose (55 - 70%, P<0.001), hydrogen peroxide (11 - 12%, P<0.01) and nitrite/nitrate (20 - 34%, P<0.01 - 0.05). The peptide prevented sucrose-induced reduction in total and non-protein thiols (1.9 - 2.0-fold, P<0.05) levels and activities of catalase (2.3 - 3.1-fold, P<0.001) and glutathione-s-transferase (1.8 - 2.8-fold, P<0.001- 0.05). Magainin-AM2 inhibited sucrose-induced reduction in acetylcholinesterase activities (3.6 - 4.0-fold, P<0.001), eclosion rate (18%, P<0.001) and negative geotaxis (1.3 - 14-fold, P<0.001). These results indicate that beneficial actions of magainin-AM2 may also involve the prevention of hyperglycaemia-induced oxidative damage and encourage its further development as an anti-diabetic agent.

2.
Immunity ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38876098

RESUMO

Allogeneic T cell expansion is the primary determinant of graft-versus-host disease (GVHD), and current dogma dictates that this is driven by histocompatibility antigen disparities between donor and recipient. This paradigm represents a closed genetic system within which donor T cells interact with peptide-major histocompatibility complexes (MHCs), though clonal interrogation remains challenging due to the sparseness of the T cell repertoire. We developed a Bayesian model using donor and recipient T cell receptor (TCR) frequencies in murine stem cell transplant systems to define limited common expansion of T cell clones across genetically identical donor-recipient pairs. A subset of donor CD4+ T cell clonotypes differentially expanded in identical recipients and were microbiota dependent. Microbiota-specific T cells augmented GVHD lethality and could target microbial antigens presented by gastrointestinal epithelium during an alloreactive response. The microbiota serves as a source of cognate antigens that contribute to clonotypic T cell expansion and the induction of GVHD independent of donor-recipient genetics.

3.
Parasit Vectors ; 17(1): 279, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943214

RESUMO

BACKGROUND: Reliance on praziquantel for the treatment and control of schistosomiasis is likely to facilitate the emergence of drug resistance. Combination therapy targeting adult and juvenile schistosome worms is urgently needed to improve praziquantel efficacy and delay the potential development of drug resistance. We assessed the efficacy and safety of single-dose praziquantel combined with single-dose artesunate plus sulfalene-pyrimethamine in the treatment of Kenyan children with schistosomiasis. METHODS: This was an open-label, randomised clinical trial involving 426 school-aged children (7-15 years old) diagnosed with Schistosoma mansoni (by Kato-Katz) or S. haematobium (by urine filtration). They were randomly assigned (1:1:1) to receive a single dose of praziquantel (40 mg/kg), a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate) or combination therapy using a single dose of praziquantel (40 mg/kg) combined with a single dose of artesunate plus sulfalene-pyrimethamine (12 mg/kg artesunate). The primary outcome was cure and egg reduction rates at 6 weeks post-treatment in the available case population. Adverse events were assessed within 3 h after treatment. RESULTS: Of the 426 children enrolled, 135 received praziquantel, 150 received artesunate plus sulfalene-pyrimethamine, and 141 received combination therapy. Outcome data were available for 348 (81.7%) children. For S. mansoni-infected children (n = 335), the cure rates were 75.6%, 60.7%, and 77.8%, and the egg reduction rates were 80.1%, 85.0%, and 88.4% for praziquantel, artesunate plus sulfalene-pyrimethamine, and combination therapy, respectively. For S. haematobium-infected children (n = 145), the corresponding cure rates were 81.4%, 71.1%, and 82.2%, and the egg reduction rates were 95.6%, 97.1%, and 97.7%, respectively. Seventy-one (16.7%) children reported mild-intensity adverse events. The drugs were well tolerated and no serious adverse events were reported. CONCLUSIONS: A single oral dose of praziquantel combined with artesunate plus sulfalene-pyrimethamine cured a high proportion of children with S. haematobium but did not significantly improve the treatment efficacy for either urinary or intestinal schistosomiasis. Sequential administration of praziquantel and artesunate plus sulfalene-pyrimethamine may enhance the efficacy and safety outcomes.


Assuntos
Anti-Helmínticos , Artemisininas , Artesunato , Quimioterapia Combinada , Praziquantel , Pirimetamina , Schistosoma haematobium , Schistosoma mansoni , Esquistossomose Urinária , Esquistossomose mansoni , Humanos , Criança , Praziquantel/administração & dosagem , Praziquantel/efeitos adversos , Praziquantel/uso terapêutico , Pirimetamina/administração & dosagem , Pirimetamina/uso terapêutico , Pirimetamina/efeitos adversos , Animais , Adolescente , Artesunato/administração & dosagem , Artesunato/uso terapêutico , Feminino , Masculino , Esquistossomose mansoni/tratamento farmacológico , Schistosoma haematobium/efeitos dos fármacos , Esquistossomose Urinária/tratamento farmacológico , Schistosoma mansoni/efeitos dos fármacos , Quênia , Artemisininas/administração & dosagem , Artemisininas/uso terapêutico , Artemisininas/efeitos adversos , Resultado do Tratamento , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/efeitos adversos , Anti-Helmínticos/uso terapêutico , Sulfaleno/administração & dosagem , Sulfaleno/uso terapêutico , Sulfaleno/efeitos adversos , Combinação de Medicamentos , Contagem de Ovos de Parasitas
4.
Mucosal Immunol ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38945396

RESUMO

Intestinal stromal cells (SCs), which synthesize the extracellular matrix that gives the mucosa its structure, are newly appreciated to play a role in mucosal inflammation. Here we show that human intestinal vimentin+CD90+SMA- SCs synthesize retinoic acid (RA) at levels equivalent to intestinal epithelial cells, a function in the human intestine previously attributed exclusively to epithelial cells. Crohn's disease SCs (Crohn's SCs), however, synthesized markedly less RA than SCs from healthy intestine (Normal SCs). We also show that microbe-stimulated Crohn's SCs, which are more inflammatory than stimulated Normal SCs, induced less RA-regulated differentiation of mucosal DCS (circulating pre-DCs and monocyte-derived DCs), leading to the generation of more potent inflammatory IFN-γhi/IL-17hi T cells than Normal SCs. Explaining these results, Crohn's SCs expressed more DHRS3, a retinaldehyde reductase that inhibits retinol conversion to retinal, and thus synthesized less RA than Normal SCs. These findings uncover a microbe-SC-DC crosstalk in which luminal microbes induce Crohn's disease SCs to initiate and perpetuate inflammation through impaired synthesis of RA.

5.
PLoS One ; 19(6): e0298585, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38900782

RESUMO

Single nucleotide polymorphisms (SNPs) in the Plasmodium falciparum multi-drug resistance protein 1 (Pfmrp1) gene have previously been reported to confer resistance to Artemisinin-based Combination Therapies (ACTs) in Southeast Asia. A total of 300 samples collected from six sites between 2008 and 2019 under an ongoing malaria drug sensitivity patterns in Kenya study were evaluated for the presence of SNPs at Pfmrp1 gene codons: H191Y, S437A, I876V, and F1390I using the Agena MassARRAY® platform. Each isolate was further tested against artemisinin (ART), lumefantrine (LU), amodiaquine (AQ), mefloquine (MQ), quinine (QN), and chloroquine (CQ) using malaria the SYBR Green I-based method to determine their in vitro drug sensitivity. Of the samples genotyped, polymorphism at Pfmrp1 codon I876V was the most frequent, with 59.3% (163/275) mutants, followed by F1390I, 7.2% (20/278), H191Y, 4.0% (6/151), and S437A, 3.3% (9/274). A significant decrease in median 50% inhibition concentrations (IC50s) and interquartile range (IQR) was noted; AQ from 2.996 ng/ml [IQR = 2.604-4.747, n = 51] in 2008 to 1.495 ng/ml [IQR = 0.7134-3.318, n = 40] (P<0.001) in 2019, QN from 59.64 ng/ml [IQR = 29.88-80.89, n = 51] in 2008 to 18.10 ng/ml [IQR = 11.81-26.92, n = 42] (P<0.001) in 2019, CQ from 35.19 ng/ml [IQR = 16.99-71.20, n = 30] in 2008 to 6.699 ng/ml [IQR = 4.976-9.875, n = 37] (P<0.001) in 2019, and ART from 2.680 ng/ml [IQR = 1.608-4.857, n = 57] in 2008 to 2.105 ng/ml [IQR = 1.266-3.267, n = 47] (P = 0.0012) in 2019, implying increasing parasite sensitivity to the drugs over time. However, no significant variations were observed in LU (P = 0.2692) and MQ (P = 0.0939) respectively, suggesting stable parasite responses over time. There was no statistical significance between the mutation at 876 and parasite sensitivity to selected antimalarials tested, suggesting stable sensitivity for the parasites with 876V mutations. These findings show that Kenyan parasite strains are still sensitive to AQ, QN, CQ, ART, LU, and MQ. Despite the presence of Pfmrp1 mutations in parasites among the population.


Assuntos
Antimaláricos , Combinação Arteméter e Lumefantrina , Malária Falciparum , Plasmodium falciparum , Polimorfismo de Nucleotídeo Único , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Humanos , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/genética , Combinação Arteméter e Lumefantrina/uso terapêutico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/parasitologia , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Quênia , Mefloquina/farmacologia , Mefloquina/uso terapêutico , Amodiaquina/farmacologia , Amodiaquina/uso terapêutico , Resistência a Medicamentos/genética , Artemisininas/farmacologia , Artemisininas/uso terapêutico , Cloroquina/farmacologia , Cloroquina/uso terapêutico , Quinina/farmacologia , Quinina/uso terapêutico , Masculino , Feminino
6.
J Hazard Mater ; 475: 134864, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38876025

RESUMO

Conventional environmental health research is primarily focused on isolated chemical exposures, neglecting the complex interactions between multiple pollutants that may synergistically or antagonistically influence toxicity, thereby posing unexpected health risks. In this study, we address this knowledge gap by introducing an explainable machine learning (ML) approach with Feature Localized Intercept Transformed-Shapley Additive Explanations (FLIT-SHAP) designed to extract the dose-response relationships of specific pollutants in mixtures. In contrast to traditional SHAP, FLIT-SHAP can localize the global intercept to elucidate mixture effects, which is crucial for understanding the oxidative potential (OP) of ambient particulate matter (PM). Assessing multi-pollutant OP using FLIT-SHAP revealed both synergistic (55-63 %) and antagonistic (25-42 %) effects in laboratory-controlled OP data, but an antagonistic (33-66 %; lower OP) effect in ambient PM. Notably, the FLIT-SHAP approach demonstrated higher prediction accuracy (R2 = 0.99) compared to the additive model (R2 = 0.89) when evaluated against real-world PM samples. Quinones, such as phenanthrenequinone, play a more significant role in PM2.5 than previously recognized. Through this study, we highlighted the potential of FLIT-SHAP to enhance toxicity predictions and aid decision-making in the field of environmental health.

7.
Biomedicines ; 12(6)2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38927483

RESUMO

The changes in endometrial cells, both in the eutopic endometrium of patients with and without endometriosis and in lesions at ectopic sites, are frequently described and often compared to tumorigenesis. In tumorigenesis, the concept of "seed and soil" is well established. The seed refers to tumor cells with metastatic potential, and the soil is any organ or tissue that provides a suitable environment for the seed to grow. In this systematic review (PRISMA-S), we specifically compared the development of endometriosis with the "seed and soil" hypothesis. To determine changes in the endometrial seed, we re-analyzed the mRNA expression data of the eutopic and ectopic endometrium, paying special attention to the epithelial-mesenchymal transition (EMT). We found that the similarity between eutopic endometrium without and with endometriosis is extremely high (~99.1%). In contrast, the eutopic endometrium of patients with endometriosis has a similarity of only 95.3% with the ectopic endometrium. An analysis of EMT-associated genes revealed only minor differences in the mRNA expression levels of claudin family members without the loss of other cell-cell junctions that are critical for the epithelial phenotype. The array data suggest that the changes in the eutopic endometrium (=seed) are quite subtle at the beginning of the disease and that most of the differences occur after implantation into ectopic locations (=soil).

8.
Cureus ; 16(4): e57410, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38694655

RESUMO

BACKGROUND: In patients with chronic liver disease, the common endpoint of its course is liver cirrhosis which is a cause of cardiovascular morbidity and mortality. These abnormalities in the cardiovascular system, especially the heart, can be detected by echocardiography. Identifying and acting on these abnormalities can have an impact on their management thereby reducing morbidity and mortality of patients with liver cirrhosis. The aim of this study was to determine the prevalence of right ventricular systolic and diastolic dysfunction in liver cirrhosis patients. METHODS AND MATERIALS: A hospital-based cross-sectional study was conducted among adult patients of the gastroenterology unit (ward and clinic) diagnosed with liver cirrhosis. A total of 243 patients were recruited and 210 were evaluated for this study. This study was carried out over one year. Cardiology studies, including electrocardiography and echocardiography, were conducted on patients to assess right ventricular function. RESULTS: Among the participants, 44.8% had right ventricular hypertrophy and 3.8% had right ventricular dilatation. Using Tricuspid Annular Plane Systolic Excursion (TAPSE), 17.1% were found to have right ventricular systolic dysfunction and 51.4% had systolic dysfunction using FAC. Diastolic dysfunction was found in 61% of the participants and grade 2 diastolic dysfunction was the commonest. CONCLUSION: From this study, a high prevalence of right ventricular systolic and diastolic dysfunction was recorded among patients with liver cirrhosis.

9.
Cureus ; 16(3): e57313, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38690468

RESUMO

BACKGROUND: Liver cirrhosis (LC) is a common complication of chronic liver disease. Its prevalence has increased markedly over the last few years. With liver cirrhosis comes cardiovascular morbidity and mortality. It is important that the detection of the abnormalities by echocardiography be given priority, as this can change the clinical outcome of these patients with cardiovascular abnormalities in liver cirrhosis. AIM: This study aims to determine the prevalence of pulmonary hypertension in LC patients. METHODS AND MATERIALS: A cross-sectional analytical study was carried out at JUTH (Jos University Teaching Hospital) over a period of one year. We recruited 210 adult patients with liver cirrhosis from the gastroenterology clinic and wards for this study. Data from these patients were collected with questionnaires administered by the interviewer and analysed using SPSS 23 statistical software (IBM Corp., Armonk, NY). The data obtained are presented in tables and charts. Categorical variables were expressed as proportions and frequencies, while continuous data were expressed as the median, mean, and standard deviation. RESULTS: Pulmonary hypertension was found in 30.5% of the participants, with mild pulmonary hypertension being the most common. No one had severe pulmonary hypertension. There was an increased risk of developing pulmonary hypertension in patients with coughs, easy fatigability, bilateral leg swelling, abdominal swelling, and ascites (P<0.05). CONCLUSION: The result showed that there is a high prevalence of pulmonary hypertension in patients with liver cirrhosis.

10.
Int J Phytoremediation ; : 1-8, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712857

RESUMO

The studies showed the effectiveness of green-synthesized SiO2NPs in mitigating the toxicity of Arsenic. Density Functional Theory (DFT) is a computational method used to determine electronic structure, energy gap, and toxicity prediction. Experimentally, silicon nanoparticles of 0 (S0) and 100% v/v (S100) were applied to the surface of the soil. 150 mL of Arsenic trioxide was applied twice at a rate of 0 (As0) and 3.2 g/mL (As3.2) at an interval of three weeks. Green synthesized SiO2NPs possessed a higher chemical potential (µ) and electrophilicity index; consequently, charges could be transferred and easily polarized. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) levels of the green synthesized SiO2NPs enable them to donate electrons and complex with arsenic, reducing their bioavailability and toxicity. Evidence from the studies further showed that SiO2NPs had buffered the soil acidity and electric conductivity, posing a high binding site and reactivity with exchangeable cations and micronutrients due to their smaller energy gap. Furthermore, the catalytic activities of the soil enzymes dehydrogenase (DHA) and peroxidase (POD) were greatly increased, which enhanced the electrostatic interaction between the SiO2NPs and As.

11.
Environ Sci Technol ; 58(20): 8835-8845, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38722766

RESUMO

Volatile methyl siloxanes (VMS) are a group of organosilicon compounds of interest because of their potential health effects, their ability to form secondary organic aerosols, and their use as tracer compounds. VMS are emitted in the gas-phase from using consumer and personal care products, including deodorants, lotions, and hair conditioners. Because of this emission route, airborne concentrations are expected to increase with population density, although there are few studies in large urban centers. Here, we report summertime concentrations and daily variations of VMS congeners measured in New York City. Median concentrations of the 6 studied congeners, D3 (20 ng m-3), D4 (57 ng m-3), D5 (230 ng m-3), D6 (11 ng m-3), L5 (2.5 ng m-3), and L7 (1.3 ng m-3) are among the highest reported outdoor concentrations in the literature to date. Average congener ratios of D5:D4 and D5:D6 were consistent with previously reported emissions ratios, suggesting that concentrations were dominated by local emissions. Measured concentrations agree with previously published results from a Community Multiscale Air Quality model and support commonly accepted emissions rates for D4, D5, and D6 of 32.8, 135, and 6.1 mg per capita per day. Concentrations of D4, D5, D6, L5, and L7 and total VMS were significantly lower during the day than during the night, consistent with daytime oxidation reactivity. Concentrations of D3 did not show the same diurnal trend but exhibited a strong directional dependence, suggesting that it may be emitted by industrial point sources in the area rather than personal care product use. Concentrations of all congeners had large temporal variations but showed relatively weak relationships with wind speed, temperature, and mixing height.


Assuntos
Poluentes Atmosféricos , Monitoramento Ambiental , Siloxanas , Cidade de Nova Iorque , Siloxanas/análise , Poluentes Atmosféricos/análise , Indústrias , Humanos , Volatilização , Estações do Ano , Cosméticos/análise , Compostos Orgânicos Voláteis/análise
12.
ACS EST Air ; 1(5): 365-375, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38751609

RESUMO

Decamethylcyclopentasiloxane (D5), a common ingredient in many personal care products (PCPs), undergoes oxidation in the atmosphere, leading to the formation of secondary organic aerosol (SOA). Yet, the specific contributions of D5-derived SOA on ambient fine particulate matter (PM2.5) have not been characterized. This study addresses this knowledge gap by introducing a new analytical method to advance the molecular characterization of oxidized D5 and its detection in ambient aerosol. The newly developed reversed phase liquid chromatography method, in conjunction with high-resolution mass spectrometry, separates and detects D5 oxidation products, enabling new insights into their molecular and isomeric composition. Application of this method to laboratory-generated SOA and urban PM2.5 in New York City expands the number of D5 oxidation products observed in ambient aerosol and informs a list of molecular candidates to track D5-derived SOA in the atmosphere. An oxidation series was observed in which one or more methyl groups in D5 (C10H30O5Si5) is replaced by a hydroxyl group, which indicates the presence of multistep oxidation products in ambient PM2.5. Because of their specificity to PCPs and demonstrated detectability in ambient PM2.5, several oxidation products are proposed as molecular tracers for D5-derived SOA and may prove useful in assessing the impact of PCPs-derived SOA in the atmosphere.

13.
Nat Commun ; 15(1): 4661, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38821972

RESUMO

Selection causes local adaptation across populations within species and simultaneously divergence between species. However, it is unclear if either the force of or the response to selection is similar across these scales. We show that natural selection drives divergence between closely related species in a pattern that is distinct from local adaptation within species. We use reciprocal transplant experiments across three species of Phlox wildflowers to characterize widespread adaptive divergence. Using provenance trials, we also find strong local adaptation between populations within a species. Comparing divergence and selection between these two scales of diversity we discover that one suite of traits predicts fitness differences between species and that an independent suite of traits predicts fitness variation within species. Selection drives divergence between species, contributing to speciation, while simultaneously favoring extensive diversity that is maintained across populations within a species. Our work demonstrates how the selection landscape is complex and multidimensional.


Assuntos
Seleção Genética , Adaptação Fisiológica/genética , Especificidade da Espécie , Especiação Genética , Aptidão Genética
14.
Heliyon ; 10(7): e29059, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38596046

RESUMO

Tanzania has a diverse agroecological area suitable for growing tropical fruits, including avocados. In Northern Tanzania, avocados have been growing under variable soil and altitudinal characteristics for over 100 years, allowing the naturalisation of this crop in this region. However, the region's avocado germplasm is uncharacterised, thus impeding the selection of elite genotypes for increased value and breeding programmes. This study examined the growth and fruit morphometric characteristics of avocado populations grown under variable soil pH and altitude in six districts in the Tanga, Kilimanjaro and Arusha regions. Variations in growth and fruit morphometric characteristics were compared using a one-way analysis of variance (ANOVA). Pearson product-moment correlations (r) were used to evaluate the relationship between studied growth and fruit morphometric traits. A linear mixed-effects model (LMM) was used to assess the influence of the soil pH, altitude, tree height, canopy diameter, and trunk diameter on fruit length, fruit diameter, pulp thickness, and seed diameter. Principal Component Analysis (PCA) was used to depict the extent of the racial admixtures in the avocado germplasm in the Northern regions of Tanzania. The results revealed a significant variation in growth and fruit morphometric characteristics (p < 0.05). The Korogwe population had the highest tree height, while the Karatu had the lowest. Tree height was positively correlated with the trunk diameter (r = 0.63, p < 0.001. There was a positive correlation between fruit length and pulp thickness (r = 0.51, p < 0.001), fruit diameter and pulp thickness (r = 0.47, p < 0.001), and fruit length and fruit diameter (r = 0.36, p < 0.001). The fruit diameter was positively correlated with the seed diameter (r = 0.61, p < 0.001). There was a significant but weak association between fruit length and trunk diameter (-0.01), fruit length and canopy diameter (0.15), and between seed diameter and tree height (2.95e-2). These findings highlight the influence of individual tree genetic makeup on the variation in growth and fruit morphometric characteristics. The morphometric trait correlations may prove valuable in field measurements, especially when resources are limited. The study further indicates the presence of all avocado races within the local germplasm, highlighting its high diversity. Remarkably, the observed admixture of variant races implies gene flow among studied avocado populations, possibly facilitated by sharing seedlings among farmers or seed disposal through avocado fruit trading. Further study is needed, particularly in quantifying the above-ground biomass of local avocados in northern Tanzania, potentially contributing to carbon credit initiatives for fruit crops..

15.
Front Cell Infect Microbiol ; 14: 1352810, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601738

RESUMO

Commensal gut bacteria use oleate hydratase to release a spectrum of hydroxylated fatty acids using host-derived unsaturated fatty acids. These compounds are thought to attenuate the immune response, but the underlying signaling mechanism(s) remain to be established. The pathogen Staphylococcus aureus also expresses an oleate hydratase and 10-hydroxyoctadecanoic acid (h18:0) is the most abundant oleate hydratase metabolite found at Staphylococcal skin infection sites. Here, we show h18:0 stimulates the transcription of a set of lipid metabolism genes associated with the activation of peroxisome proliferator activated receptor (PPAR) in the RAW 264.7 macrophage cell line and mouse primary bone marrow-derived macrophages. Cell-based transcriptional reporter assays show h18:0 selectively activates PPARα. Radiolabeling experiments with bone marrow-derived macrophages show [1-14C]h18:0 is not incorporated into cellular lipids, but is degraded by ß-oxidation, and mass spectrometry detected shortened fragments of h18:0 released into the media. The catabolism of h18:0 was >10-fold lower in bone marrow-derived macrophages isolated from Ppara -/- knockout mice, and we recover 74-fold fewer S. aureus cells from the skin infection site of Ppara -/- knockout mice compared to wildtype mice. These data identify PPARα as a target for oleate hydratase-derived hydroxy fatty acids and support the existence of an oleate hydratase-PPARα signaling axis that functions to suppress the innate immune response to S. aureus.


Assuntos
PPAR alfa , Staphylococcus aureus , Camundongos , Animais , PPAR alfa/metabolismo , Staphylococcus aureus/metabolismo , Ácido Oleico , Ácidos Graxos/metabolismo , Camundongos Knockout
16.
PLoS One ; 19(4): e0300050, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38574045

RESUMO

The quantification of aerosol size distributions is crucial for understanding the climate and health impacts of aerosols, validating models, and identifying aerosol sources. This work provides one of the first continuous measurements of aerosol size distribution from 1.02 to 8671 nm near the shore of Lake Michigan. The data were collected during the Lake Michigan Ozone Study (LMOS 2017), a comprehensive air quality measurement campaign in May and June 2017. The time-resolved (2-min) size distribution are reported herein alongside meteorology, remotely sensed data, gravimetric filters, and gas-phase variables. Mean concentrations of key aerosol parameters include PM2.5 (6.4 µg m-3), number from 1 to 3 nm (1.80x104 cm-3) and number greater than 3 nm (8x103 cm-3). During the field campaign, approximately half of days showed daytime ultrafine burst events, characterized by particle growth from sub 10 nm to 25-100 nm. A specific investigation of ultrafine lake spray aerosol was conducted due to enhanced ultrafine particles in onshore flows coupled with sustained wave breaking conditions during the campaign. Upon closer examination, the relationships between the size distribution, wind direction, wind speed, and wave height did not qualitatively support ultrafine particle production from lake spray aerosol; statistical analysis of particle number and wind speed also failed to show a relationship. The alternative hypothesis of enhanced ultrafine particles in onshore flow originating mainly from new particle formation activity is supported by multiple lines of evidence.


Assuntos
Poluentes Atmosféricos , Lagos , Lagos/análise , Tamanho da Partícula , Partículas e Gotas Aerossolizadas , Material Particulado/análise , Aerossóis/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental
17.
Zoonoses Public Health ; 71(5): 503-514, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38627945

RESUMO

AIMS: Q fever is a globally distributed, neglected zoonotic disease of conservation and public health importance, caused by the bacterium Coxiella burnetii. Coxiella burnetii normally causes subclinical infections in livestock, but may also cause reproductive pathology and spontaneous abortions in artiodactyl species. One such artiodactyl, the dromedary camel (Camelus dromedarius), is an increasingly important livestock species in semi-arid landscapes. Ticks are naturally infected with C. burnetii worldwide and are frequently found on camels in Kenya. In this study, we assessed the relationship between dromedary camels' C. burnetii serostatus and whether the camels were carrying C. burnetii PCR-positive ticks in Kenya. We hypothesized that there would be a positive association between camel seropositivity and carrying C. burnetii PCR-positive ticks. METHODS AND RESULTS: Blood was collected from camels (N = 233) from three herds, and serum was analysed using commercial ELISA antibody test kits. Ticks were collected (N = 4354), divided into pools of the same species from the same camel (N = 397) and tested for C. burnetii and Coxiella-like endosymbionts. Descriptive statistics were used to summarize seroprevalence by camel demographic and clinical variables. Univariate logistic regression analyses were used to assess relationships between serostatus (outcome) and tick PCR status, camel demographic variables, and camel clinical variables (predictors). Camel C. burnetii seroprevalence was 52%. Across tick pools, the prevalence of C. burnetii was 15% and Coxiella-like endosymbionts was 27%. Camel seropositivity was significantly associated with the presence of a C. burnetii PCR-positive tick pool (OR: 2.58; 95% CI: 1.4-5.1; p = 0.0045), increasing age class, and increasing total solids. CONCLUSIONS: The role of ticks and camels in the epidemiology of Q fever warrants further research to better understand this zoonotic disease that has potential to cause illness and reproductive losses in humans, livestock, and wildlife.


Assuntos
Camelus , Coxiella burnetii , Febre Q , Animais , Camelus/microbiologia , Coxiella burnetii/isolamento & purificação , Coxiella burnetii/genética , Febre Q/epidemiologia , Febre Q/veterinária , Febre Q/microbiologia , Quênia/epidemiologia , Masculino , Estudos Soroepidemiológicos , Feminino , DNA Bacteriano , Carrapatos/microbiologia , Infestações por Carrapato/veterinária , Infestações por Carrapato/epidemiologia
18.
Sci Rep ; 14(1): 6176, 2024 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486015

RESUMO

Arsenic (As) is a heavy metal that is toxic to both plants and animals. Silicon nanoparticles (SiNPs) can alleviate the detrimental effects of heavy metals on plants, but the underlying mechanisms remain unclear. The study aims to synthesize SiNPs and reveal how they promote plant health in Arsenic-polluted soil. 0 and 100% v/v SiNPs were applied to soil, and Arsenic 0 and 3.2 g/ml were applied twice. Maize growth was monitored until maturity. Small, irregular, spherical, smooth, and non-agglomerated SiNPs with a peak absorbance of 400 nm were synthesized from Pycreus polystachyos. The SiNPs (100%) assisted in the development of a deep, prolific root structure that aided hydraulic conductance and gave mechanical support to the maize plant under As stress. Thus, there was a 40-50% increase in growth, tripled yield weights, and accelerated flowering, fruiting, and senescence. SiNPs caused immobilization (As(III)=SiNPs) of As in the soil and induced root exudates Phytochelatins (PCs) (desGly-PC2 and Oxidized Glutathione) which may lead to formation of SiNPs=As(III)-PCs complexes and sequestration of As in the plant biomass. Moreover, SiNPs may alleviate Arsenic stress by serving as co-enzymes that activate the antioxidant-defensive mechanisms of the shoot and root. Thus, above 70%, most reactive ROS (OH) were scavenged, which was evident in the reduced MDA content that strengthened the plasma membrane to support selective ion absorption of SiNPs in place of Arsenic. We conclude that SiNPs can alleviate As stress through sequestration with PCs, improve root hydraulic conductance, antioxidant activity, and membrane stability in maize plants, and could be a potential tool to promote heavy metal stress resilience in the field.


Assuntos
Arsênio , Metais Pesados , Nanopartículas , Antioxidantes/metabolismo , Arsênio/metabolismo , Metais Pesados/metabolismo , Nanopartículas/química , Fitoquelatinas/metabolismo , Plantas/metabolismo , Silício/farmacologia , Solo , Zea mays/metabolismo
19.
Artigo em Inglês | MEDLINE | ID: mdl-38526060

RESUMO

OBJECTIVE: To determine in adult chickens which of 3 CPR techniques, sternal compressions (SC), SC with interposed caudal coelomic compressions (ICCC), or lateral compressions (LC), results in the highest mean systolic (SAP), diastolic (DAP), and mean arterial pressure (MAP) as measured directly from the carotid artery. DESIGN: Prospective, nonblinded, experimental crossover study. SETTING: University teaching hospital laboratory. ANIMALS: Ten retired laying hens. INTERVENTIONS: Birds were sedated, anesthetized, and placed in dorsal recumbency. A carotid artery catheter was placed to directly measure arterial pressure. Ventricular fibrillation was induced with direct cardiac stimulation using a 9-Volt battery. Each bird then received 2 minutes of the 3 different cardiac compression techniques in a random order by 3 different compressors, with the compressor order also randomized. Birds were subsequently administered IV epinephrine, and transthoracic defibrillation was attempted. At the end of experimentation, each bird was euthanized, and simple gross necropsies were performed. Linear mixed models followed by pairwise paired t-tests were performed to evaluate differences in pressures generated by each technique. MEASUREMENTS AND MAIN RESULTS: The primary study outcomes were SAP, DAP, and MAP over 2 minutes of compressions for each compression technique. Pressures from ICCC (SAP: 27.6 ± 5.3 mm Hg, DAP: 18.7 ± 5.2 mm Hg, MAP: 21.7 ± 5.2 mm Hg) were significantly higher than those from LC (SAP: 18.9 ± 5.4 mm Hg, DAP: 11.6 ± 4.1 mm Hg, MAP: 14.1 ± 4.5 mm Hg). Pressures from SC (SAP: 24.5 ± 6.4 mm Hg, DAP: 15.2 ± 4.3 mm Hg, MAP: 18.3 ± 5.0 mm Hg) were not significantly different from ICCC or LC. CONCLUSIONS: External compressions can generate detectable increases in arterial pressure in chickens with ventricular fibrillation. SC with ICCC generated significantly higher arterial pressures than LC. SC alone generated blood pressures that were not significantly different from those generated by SC with ICCC or LC.


Assuntos
Reanimação Cardiopulmonar , Galinhas , Animais , Feminino , Humanos , Pressão Sanguínea/fisiologia , Reanimação Cardiopulmonar/veterinária , Reanimação Cardiopulmonar/métodos , Estudos Cross-Over , Estudos Prospectivos , Fibrilação Ventricular/veterinária , Estudo de Prova de Conceito
20.
Am J Trop Med Hyg ; 110(4): 677-680, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38460198

RESUMO

Unlike praziquantel, artemisinin derivatives are effective against juvenile schistosome worms. We assessed the efficacy and safety of a single oral dose of artesunate plus sulfalene-pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni. Seventy-three schoolchildren (aged 9-15 years) with confirmed S. mansoni infection in Rarieda, western Kenya, were randomly assigned to receive either a single oral dose of artesunate plus sulfalene-pyrimethamine (n = 39) or a single dose of praziquantel (n = 34). The cure and egg reduction rates at 4 weeks posttreatment were 69.4% (25/36) versus 80.6% (25/31) (P = 0.297) and 99.1% versus 97.5% (P = 0.607) in the artesunate plus sulfalene-pyrimethamine group versus praziquantel group, respectively. Fourteen children developed adverse events, and there were no serious adverse events. A single oral dose of artesunate plus sulfalene-pyrimethamine has efficacy comparable to that of praziquantel in the treatment of S. mansoni, but these results should be confirmed in larger randomized controlled trials.


Assuntos
Anti-Helmínticos , Artemisininas , Esquistossomose mansoni , Sulfaleno , Adolescente , Animais , Criança , Humanos , Anti-Helmínticos/uso terapêutico , Artemisininas/efeitos adversos , Artesunato/uso terapêutico , Quimioterapia Combinada , População da África Oriental , Quênia , Praziquantel/efeitos adversos , Pirimetamina/uso terapêutico , Schistosoma mansoni , Esquistossomose mansoni/tratamento farmacológico , Sulfaleno/farmacologia , Sulfaleno/uso terapêutico , Resultado do Tratamento
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