Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 333
Filtrar
1.
Artículo en Inglés | MEDLINE | ID: mdl-39172146

RESUMEN

Ethanol consumption induces thymic atrophy and affects T cell maturation in the thymus. However, the mechanisms underlying such effects still need to be fully understood. We attempted to investigate the role of mineralocorticoid receptors (MR) on ethanol-induced thymic atrophy, T cell maturation dysfunction, and the role of oxidative stress in such responses. Male Wistar Hannover rats were treated with ethanol (20%; in volume ratio) and/or potassium canrenoate, an antagonist of MR (MRA; 30 mg/kg/day, gavage) for five weeks. Blockade of MR prevented ethanol-induced increases in the number of double-positive (CD4+CD8+), CD8+ single-positive (CD4-CD8+), CD4+ single-positive (CD4+CD8-), and Foxp3+CD4+ (Treg) cells in the thymus. Ethanol increased NOX2-derived superoxide (O2•-), lipoperoxidation, and superoxide dismutase (SOD) activity in the thymus. Pretreatment with the MRA fully prevented these responses. Apocynin, an antioxidant, prevented ethanol-induced increases in the number of double-positive and CD8+ single-positive cells but failed to prevent the rise in the number of CD4+ single-positive and Treg cells induced by ethanol. Apocynin, but not the MRA, prevented thymic atrophy induced by ethanol. Our findings provided novel evidence for the participation of MR in thymic dysfunction induced by ethanol consumption. Oxidative stress mediates the increase in double-positive and CD8+ single-positive cells in response to MR activation, while positive regulation of CD4+ single-positive and Treg cells is independent of oxidative stress. Oxidative stress is a significant mechanism of thymic atrophy associated with ethanol consumption, but this response is independent of MR activation.

2.
Vaccine ; 42(21): 126141, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39033080

RESUMEN

Amblyomma sculptum is widely distributed in Brazil and is the main vector of Rickettsia rickettsii, the causative agent of the Brazilian spotted fever (BSF). Tick gut proteins play an essential role in blood feeding, digestion, and protection of gut epithelium. Therefore, many of these were investigated as potential vaccine targets for tick-control strategies. The present study aimed to select transcripts corresponding to putative immunogenic proteins in the A. sculptum gut epithelial membrane, produce recombinant proteins and evaluate them as antigens against A. sculptum infestations. Three gut proteins - AsMucin, AsAPP, and AsLAMP - and a chimeric protein (rAsChimera) based on 22 peptides containing putative B cell epitopes from seven different gut proteins were evaluated as anti-A. sculptum antigens. Mice immunizations revealed that all recombinant targets elicited humoral response with significantly increased IgG levels compared to controls. For rAsChimera, IgG levels remained significantly higher than controls up to 75 days after the end of the immunization. Challenge trials revealed that vaccination with the chimeric protein was the most effective against A. sculptum, inducing 100 % nymph mortality and reaching 80.8 % efficacy against females. The other three proteins did not induce relevant protection, as AsAPP had only 26.6 % efficacy, whereas AsMucin and AsLAMP induced no protection. These data indicate that targeting gut protein immunogenic regions may be an effective strategy for a vaccine formulation againstA. sculptum.


Asunto(s)
Amblyomma , Animales , Ratones , Femenino , Amblyomma/inmunología , Inmunización/métodos , Proteínas de la Membrana/inmunología , Proteínas de la Membrana/genética , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Proteínas Recombinantes/inmunología , Proteínas Recombinantes/genética , Infestaciones por Garrapatas/prevención & control , Infestaciones por Garrapatas/inmunología , Rickettsia rickettsii/inmunología , Brasil , Masculino , Ratones Endogámicos BALB C , Antígenos/inmunología
3.
Mol Microbiol ; 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720451

RESUMEN

Aedes aegypti females are natural vectors of important arboviruses such as dengue, zika, and yellow fever. Mosquitoes activate innate immune response signaling pathways upon infection, as a resistance mechanism to fight pathogens and limit their propagation. Despite the beneficial effects of immune activation for insect vectors, phenotypic costs ultimately affect their fitness. However, the underlying mechanisms that mediate these fitness costs remain poorly understood. Given the high energy required to mount a proper immune response, we hypothesized that systemic activation of innate immunity would impair flight muscle mitochondrial function, compromising tissue energy demand and flight activity. Here, we investigated the dynamic effects of activation of innate immunity by intra-thoracic zymosan injection on A. aegypti flight muscle mitochondrial metabolism. Zymosan injection significantly increased defensin A expression in fat bodies in a time-dependent manner that compromised flight activity. Although oxidant levels in flight muscle were hardly altered, ATP-linked respiratory rates driven by mitochondrial pyruvate+proline oxidation were significantly reduced at 24 h upon zymosan injection. Oxidative phosphorylation coupling was preserved regardless of innate immune response activation along 24 h. Importantly, rotenone-sensitive respiration and complex I-III activity were specifically reduced 24 h upon zymosan injection. Also, loss of complex I activity compromised ATP-linked and maximal respiratory rates mediated by mitochondrial proline oxidation. Finally, the magnitude of innate immune response activation negatively correlated with respiratory rates, regardless of the metabolic states. Collectively, we demonstrate that activation of innate immunity is strongly associated with reduced flight muscle complex I activity with direct consequences to mitochondrial proline oxidation and flight activity. Remarkably, our results indicate a trade-off between dispersal and immunity exists in an insect vector, underscoring the potential consequences of disrupted flight muscle mitochondrial energy metabolism to arbovirus transmission.

4.
Biochem Pharmacol ; 224: 116245, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38685281

RESUMEN

Cardiovascular disease (CVD) is the leading cause of death in rheumatoid arthritis (RA). Resistin is an adipokine that induces adipose tissue inflammation and activation of monocytes/macrophages via adenylate cyclase-associated protein-1 (CAP1). Resistin levels are increased in RA and might cause perivascular adipose tissue (PVAT) dysfunction, leading to vascular damage and CVD. This study aimed to investigate the role of resistin in promoting PVAT dysfunction by increasing local macrophage and inflammatory cytokines content in antigen-induced arthritis (AIA). Resistin pharmacological effects were assessed by using C57Bl/6J wild-type (WT) mice, humanized resistin mice expressing human resistin in monocytes-macrophages (hRTN+/-/-), and resistin knockout mice (RTN-/-) with AIA and respective controls. We investigated AIA disease activity and functional, cellular, and molecular parameters of the PVAT. Resistin did not contribute to AIA disease activity and its concentrations were augmented in the PVAT and plasma of WT AIA and hRTN+/-/- AIA animals. In vitro exposure of murine arteries to resistin impaired vascular function by decreasing the anti-contractile effect of PVAT. WT AIA mice and hRTN+/-/- AIA mice exhibited PVAT dysfunction and knockdown of resistin prevented it. Macrophage-derived cytokines, markers of types 1 and 2 macrophages, and CAP1 expression were increased in the PVAT of resistin humanized mice with AIA, but not in knockout mice for resistin. This study reveals that macrophage-derived resistin promotes PVAT inflammation and dysfunction regardless of AIA disease activity. Resistin might represent a translational target to reduce RA-driven vascular dysfunction and CVD.


Asunto(s)
Tejido Adiposo , Artritis Experimental , Macrófagos , Ratones Endogámicos C57BL , Resistina , Animales , Resistina/metabolismo , Resistina/genética , Humanos , Tejido Adiposo/metabolismo , Ratones , Macrófagos/metabolismo , Artritis Experimental/metabolismo , Ratones Noqueados , Masculino
5.
Neotrop Entomol ; 53(3): 469-479, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38347319

RESUMEN

Pastoralism is a dominant agricultural activity in arid and semi-arid ecosystems. The interaction between coprophagous insects and livestock is a key but an undervalued topic in rangeland management decisions. The objective was to identify similarities and differences in the composition of coprophagous insects and nesting strategies, associated with different climatic conditions within these regions. We performed a literature review of research articles available in the Scopus database which resulted in 17 articles. We examined the taxonomic diversity of dung beetles and their nesting strategies in relation to temperature and precipitation at the study sites. Results revealed a rich and varied interaction between dung beetles and livestock in arid and semi-arid environments, with 364 species from the Scarabaeoidea superfamily documented worldwide. The greatest diversity of dung beetles was reported in hot arid and semi-arid conditions with dry winters and in cold semi-arid ones with no marked annual precipitation cycle. These insects displayed diverse nesting strategies, with endocoprid strategies predominating in colder and drier settings, and paracoprid and telecoprid strategies in warmer, more humid environments. Domestic animal species are currently key components in promoting this interaction, which indicates that the ecological processes involving coprophagous fauna are occurring in production systems, which are under the influence of human decisions. We discuss the design and planning of livestock and rangeland management in arid and semi-arid environments, emphasizing in a more formalized manner the inclusion of this kind of interaction.


Asunto(s)
Escarabajos , Ganado , Animales , Escarabajos/fisiología , Escarabajos/clasificación , Clima Desértico , Comportamiento de Nidificación
6.
Nat Commun ; 15(1): 1298, 2024 Feb 12.
Artículo en Inglés | MEDLINE | ID: mdl-38346955

RESUMEN

Electric control of magnetization dynamics in two-dimensional (2D) magnetic materials is an essential step for the development of novel spintronic nanodevices. Electrostatic gating has been shown to greatly affect the static magnetic properties of some van der Waals magnets, but the control over their magnetization dynamics is still largely unexplored. Here we show that the optically-induced magnetization dynamics in the van der Waals ferromagnet Cr2Ge2Te6 can be effectively controlled by electrostatic gates, with a one order of magnitude change in the precession amplitude and over 10% change in the internal effective field. In contrast to the purely thermally-induced mechanisms previously reported for 2D magnets, we find that coherent opto-magnetic phenomena play a major role in the excitation of magnetization dynamics in Cr2Ge2Te6. Our work sets the first steps towards electric control over the magnetization dynamics in 2D ferromagnetic semiconductors, demonstrating their potential for applications in ultrafast opto-magnonic devices.

7.
Artículo en Inglés | MEDLINE | ID: mdl-38224901

RESUMEN

Clogmia albipunctata (Williston, 1893) is a non-hematophagous insect belonging to the order Diptera, suborder Nematocera (Lower Diptera) and family Psychodidae. In the present work, we investigated how C. albipunctata control their midgut pH under different physiological conditions, comparing their midgut physiology with some nematoceran hematophagous species. The C. albipunctata midgut pH was measured after ingestion of sugar, protein and under the effect of the alkalinizing hormone released in the hemolymph of the hematophagous sand fly Lutzomyia longipalpis obtained just after a blood meal. The midgut pH of unfed or sugar-fed C. albipunctata is 5.5-6, and its midgut underwent alkalinization after protein ingestion or under treatment with hemolymph collected from blood fed L. longipalpis. These results suggested that in nematocerans, mechanisms for pH control seem shared between hematophagous and non-hematophagous species. This kind of pH control is convenient for successful blood digestion. The independent evolution of many hematophagous groups from the Lower Diptera suggests that characteristics involved in midgut pH control were already present in non-hematophagous species and represent a readiness for adaptation to this feeding mode.


Asunto(s)
Psychodidae , Animales , Psychodidae/fisiología , Sistema Digestivo , Concentración de Iones de Hidrógeno , Azúcares
9.
Bull Entomol Res ; 113(6): 735-747, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37855149

RESUMEN

The ecological function played by the coprophagous insects is an important issue in livestock production contexts. The role of this fauna, specially dung beetles, provides benefits to both rangelands and production performance. This interaction has been studied and reported in many scientific articles, in very different places and with diverse production contexts. However, a comprehensive review of the relationship between coprophagous insects and livestock production is still lacking. We reviewed the research studies on this topic during the past five decades, with a focus in Scarabaeidae taxon and livestock production, in order to identify further research priorities. We analysed 435 research articles. The main results were: (I) studies were mostly located in temperate broadleaf forest biome, whereas arid environments were less studied; (II) Production practices impacts category was the most studied, for which the effects produced by antiparasitic products on the coprophagous insects (n = 93; 21% of total revised articles) was the topics with major number of articles. Followed was Biology category (n = 69; 16%), then in Ecosystem function category the most frequent studies were on dung removal (n = 40; 9%), whereas in the Ecosystem Services category the most frequent studies were on biological control (n = 28; 6%); (III) Australia, Mexico, Brazil, and United States were the countries with most research articles. We identified some knowledge gaps on relevant ecological functions of this fauna, in relation to benefits to livestock production. There is a need for future research on nutrient cycling, bioturbation, effects on primary production and vegetation diversity.


Asunto(s)
Escarabajos , Ecosistema , Animales , Ganado , Insectos , Bosques , Heces
10.
Toxicol Appl Pharmacol ; 473: 116599, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37328116

RESUMEN

Studies have indicated that glyphosate induces endocrine disruption and may adversely affect the male reproductive system. However, evidence of its effects on ovarian function is poorly understood so far, making further studies necessary on the mechanisms of the glyphosate toxicity in the female reproductive system. The aim of this work was to evaluate the effect of a subacute exposure (28 days) to the glyphosate-based formulation Roundup® (1.05, 10.5 and 105 µg/kg b.w. of glyphosate) on steroidogenesis, oxidative stress, systems involved in cell redox control and histopathological parameters in rat ovaries. Hence we quantify plasma estradiol and progesterone by chemiluminescence; non-protein thiol levels, TBARS, superoxide dismutase and catalase activity by spectrophotometry; gene expression of steroidogenic enzymes and redox systems by real-time PCR; and ovarian follicles by optical microscopy. Our results demonstrated that oral exposure increased progesterone levels and the mRNA expression of 3ß-hydroxysteroid dehydrogenase. Histopathological analysis revealed a decrease in the number of primary follicles and an increase in the number of corpus luteum in rats exposed to Roundup®. An imbalance of the oxidative status was also evidenced by decreasing the catalase activity at all groups exposed to the herbicide. Increased lipid peroxidation and gene expression of glutarredoxin and decreased of glutathione reductase were also observed. Our results indicate that Roundup® causes endocrine disruption of hormones related to female fertility and reproduction and changes the oxidative status by altering antioxidant activity, inducing lipid peroxidation, as well as changing the gene expression of the glutathione-glutarredoxin system in rat ovaries.


Asunto(s)
Herbicidas , Ovario , Ratas , Masculino , Femenino , Animales , Progesterona , Catalasa/genética , Catalasa/metabolismo , Herbicidas/toxicidad , Glutarredoxinas/farmacología , Antioxidantes/farmacología , Glutatión/metabolismo , Estradiol/farmacología , Expresión Génica , Glifosato
11.
Pharmaceuticals (Basel) ; 16(4)2023 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-37111388

RESUMEN

Snake venom serine protease (SVSP) interferes with the regulation and control of important biological reactions in homeostasis and can be classified as an activator of the fibrinolytic system and platelet aggregation. Our group has recently isolated a new serine protease from Crotalus durissus terrificus total venom (Cdtsp-2). This protein exhibits edematogenic capacity and myotoxic activity. A Kunitz-like EcTI inhibitor protein with a molecular mass of 20 kDa was isolated from Enterolobium contortisiliquum and showed high trypsin inhibition. Thus, the objective of this work is to verify the possible inhibition of the pharmacological activities of Cdtsp-2 by the Kutinz-type inhibitor EcTI. To isolate Cdtsp-2 from total C. d. terrificus venom, we used three-step chromatographic HPLC. Using the mice paw edema model, we observed an edematogenic effect, myotoxicity and hepatotoxicity caused by Cdtsp-2. In vitro and in vivo experiments showed that the alterations in hemostasis caused by Cdtsp-2 are crucial for the development of marked hepatotoxicity and that EcTI significantly inhibits the enzymatic and pharmacological activities of Cdtsp-2. Kunitz-like inhibitor may be a viable alternative for the development of ancillary treatments against the biological activities of venoms.

12.
Toxicon ; 227: 107082, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36948303

RESUMEN

In recent years, morbidity caused by scorpion sting of the species Tityus championi has increased in Panama. Therefore, the LD50 was determined by intravenous injection in 2.9 mg/kg and the venom of T. championi was separated using a HPLC system and their fractions were tested for biological activities in mice to identify the most toxic fractions to mammals. In addition, the venom fractions were also tested against invertebrates to look for insect-specific toxin peptides. The most toxic fractions were analyzed by MS/MS spectrometry. The primary structures of T. championi venom peptides with the most relevant activity were obtained, and the primary structure of one of most neurotoxic peptides was found at least in other four species of Tityus from Panama. This neurotoxin is quite important to be used as a protein target to be neutralized if developing antivenoms against the sting of this Panamanian scorpion or other relevant species of genera Tityus in the country.


Asunto(s)
Venenos de Escorpión , Ponzoñas , Animales , Ratones , Ponzoñas/metabolismo , Escorpiones/química , Proteómica , Espectrometría de Masas en Tándem , Péptidos/química , Venenos de Escorpión/química , Mamíferos/metabolismo
13.
Science ; 379(6630): eabp8622, 2023 01 27.
Artículo en Inglés | MEDLINE | ID: mdl-36701452

RESUMEN

Approximately 2.5 × 106 square kilometers of the Amazon forest are currently degraded by fire, edge effects, timber extraction, and/or extreme drought, representing 38% of all remaining forests in the region. Carbon emissions from this degradation total up to 0.2 petagrams of carbon per year (Pg C year-1), which is equivalent to, if not greater than, the emissions from Amazon deforestation (0.06 to 0.21 Pg C year-1). Amazon forest degradation can reduce dry-season evapotranspiration by up to 34% and cause as much biodiversity loss as deforestation in human-modified landscapes, generating uneven socioeconomic burdens, mainly to forest dwellers. Projections indicate that degradation will remain a dominant source of carbon emissions independent of deforestation rates. Policies to tackle degradation should be integrated with efforts to curb deforestation and complemented with innovative measures addressing the disturbances that degrade the Amazon forest.


Asunto(s)
Carbono , Conservación de los Recursos Naturales , Bosque Lluvioso , Biodiversidad , Ciclo del Carbono , Brasil
14.
Med Vet Entomol ; 37(2): 238-251, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36458853

RESUMEN

Lutzomyia longipalpis is known as one of the primary insect vectors of visceral leishmaniasis. For such ectothermic organisms, the ambient temperature is a critical life factor. However, the impact of temperature has been ignored in many induced-stress situations of the vector life. Therefore, this study explored the interaction of Lu. longipalpis with temperature by evaluating its behaviour across a thermal gradient, thermographic recordings during blood-feeding on mice, and the gene expression of heat shock proteins (HSP) when insects were exposed to extreme temperature or infected. The results showed that 72 h after blood ingestion, Lu. longipalpis became less active and preferred relatively low temperatures. However, at later stages of blood digestion, females increased their activity and remained at higher temperatures. Real-time imaging showed that the body temperature of females can adjust rapidly to the host and remain constant until the end of blood-feeding. Insects also increased the expression of HSP90(83) during blood-feeding. Our findings suggest that Lu. longipalpis interacts with temperature by using its behaviour to avoid temperature-induced physiological damage during the gonotrophic cycle. However, the expression of certain HSP might be triggered to mitigate thermal stress in situations where a behavioural response is not the best option.


Asunto(s)
Leishmaniasis Visceral , Psychodidae , Femenino , Animales , Ratones , Leishmaniasis Visceral/veterinaria , Psychodidae/fisiología , Temperatura , Insectos Vectores
15.
Cannabis Cannabinoid Res ; 8(1): 41-55, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-35861789

RESUMEN

Background: Cannabinoids have been suggested to alleviate frequently experienced symptoms of reduced mental well-being such as anxiety and depression. Mental well-being is an important subdomain of health-related quality of life (HRQoL). Reducing symptoms and maintaining HRQoL are particularly important in malignant primary brain tumor patients, as treatment options are often noncurative and prognosis remains poor. These patients frequently report unprescribed cannabinoid use, presumably for symptom relieve. As studies on brain tumor patients specifically are lacking, we performed a meta-analysis of the current evidence on cannabinoid efficacy on HRQoL and mental well-being in oncological and neurological patients. Methods: We performed a systematic PubMed, PsychINFO, Embase, and Web of Science search according to PRISMA guidelines on August 2 and 3, 2021. We included randomized controlled trials (RCTs) that assessed the effects of tetrahydrocannabinol (THC) or cannabidiol (CBD) on general HRQoL and mental well-being. Pooled effect sizes were calculated using Hedges g. Risk of bias of included studies was assessed using Cochrane's Risk of Bias tool. Results: We included 17 studies: 4 in oncology and 13 in central nervous system (CNS) disease. Meta-analysis showed no effect of cannabinoids on general HRQoL (g=-0.02 confidence interval [95% CI -0.11 to 0.06]; p=0.57) or mental well-being (g=-0.02 [95% CI -0.16 to 0.13]; p=0.81). Conclusions: RCTs in patients with cancer or CNS disease showed no effect of cannabinoids on HRQoL or mental well-being. However, studies were clinically heterogeneous and since many glioma patients currently frequently use cannabinoids, future studies are necessary to evaluate its value in this specific population.


Asunto(s)
Cannabidiol , Cannabinoides , Humanos , Calidad de Vida , Dronabinol/efectos adversos , Cannabidiol/efectos adversos , Ansiedad
16.
Molecules ; 27(23)2022 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-36500705

RESUMEN

An electrochemical sensor for simultaneous determination of Benserazide (BEZ) and levodopa (L-dopa) was successfully developed using a glassy carbon electrode (GCE) modified with multi-walled carbon nanotube and nitrogen-doped titanium dioxide nanoparticles (GCE/MWCNT/N-TiO2). Cyclic voltammetry and square wave voltammetry were employed to investigate the electrochemical behavior of different working electrodes and analytes. In comparison with unmodified GCE, the modified electrode exhibited better electrocatalytic activity towards BEZ and L-dopa and was efficient in providing a satisfactory separation for oxidation peaks, with a potential difference of 140 mV clearly allows the simultaneous determination of these compounds. Under the optimized conditions, linear ranges of 2.0-20.0 and 2.0-70.0 µmol L-1 were obtained for BEZ and L-dopa, respectively, with a limit of detection of 1.6 µmol L-1 for BEZ and 2.0 µmol L-1 for L-dopa. The method was applied in simultaneous determination of the analytes in pharmaceutical samples, and the accuracy was attested by comparison with HPLC-DAD as the reference method, with a relative error lower than 4.0%.


Asunto(s)
Nanotubos de Carbono , Nanotubos de Carbono/química , Levodopa , Benserazida , Electrodos , Oxidación-Reducción , Técnicas Electroquímicas/métodos
17.
PLoS One ; 17(11): e0277680, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36395175

RESUMEN

The UK Biobank genotyped about 500k participants using Applied Biosystems Axiom microarrays. Participants were subsequently sequenced by the UK Biobank Exome Sequencing Consortium. Axiom genotyping was highly accurate in comparison to sequencing results, for almost 100,000 variants both directly genotyped on the UK Biobank Axiom array and via whole exome sequencing. However, in a study using the exome sequencing results of the first 50k individuals as reference (truth), it was observed that the positive predictive value (PPV) decreased along with the number of heterozygous array calls per variant. We developed a novel addition to the genotyping algorithm, Rare Heterozygous Adjusted (RHA), to significantly improve PPV in variants with minor allele frequency below 0.01%. The improvement in PPV was roughly equal when comparing to the exome sequencing of 50k individuals, or to the more recent ~200k individuals. Sensitivity was higher in the 200k data. The improved calling algorithm, along with enhanced quality control of array probesets, significantly improved the positive predictive value and the sensitivity of array data, making it suitable for the detection of ultra-rare variants.


Asunto(s)
Exoma , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Genotipo , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Estudios Retrospectivos , Bancos de Muestras Biológicas , Polimorfismo de Nucleótido Simple , Algoritmos , Reino Unido
18.
Nat Microbiol ; 7(6): 844-855, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35650286

RESUMEN

DNA-protein interactions are central to fundamental cellular processes, yet widely implemented technologies for measuring these interactions on a genome scale in bacteria are laborious and capture only a snapshot of binding events. We devised a facile method for mapping DNA-protein interaction sites in vivo using the double-stranded DNA-specific cytosine deaminase toxin DddA. In 3D-seq (DddA-sequencing), strains containing DddA fused to a DNA-binding protein of interest accumulate characteristic mutations in DNA sequence adjacent to sites occupied by the DNA-bound fusion protein. High-depth sequencing enables detection of sites of increased mutation frequency in these strains, yielding genome-wide maps of DNA-protein interaction sites. We validated 3D-seq for four transcription regulators in two bacterial species, Pseudomonas aeruginosa and Escherichia coli. We show that 3D-seq offers ease of implementation, the ability to record binding event signatures over time and the capacity for single-cell resolution.


Asunto(s)
Citosina Desaminasa , Genoma , Bacterias/metabolismo , ADN/metabolismo , Mapeo de Interacción de Proteínas
19.
J Thorac Imaging ; 37(4): 246-252, 2022 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-35749622

RESUMEN

PURPOSE: Our objective was to evaluate whether the normal lung index (NLI) from quantitative computed tomography (QCT) analysis can be used to predict mortality as well as pulmonary function tests (PFTs) in patients with chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). MATERIALS AND METHODS: Normal subjects (n=20) and patients with COPD (n=172) and ILD (n=114) who underwent PFTs and chest CT were enrolled retrospectively in this study. QCT measures included the NLI, defined as the ratio of the lung with attenuation between -950 and -700 Hounsfield units (HU) over the total lung volume (-1024 to -250 HU, mL), high-attenuation area (-700 to -250 HU, %), emphysema index (>6% of pixels < -950 HU), skewness, kurtosis, and mean lung attenuation. Coefficients of correlation between QCT measurements and PFT results in all subjects were calculated. Univariate and multivariate survival analyses were performed to assess mortality prediction by disease. RESULTS: The Pearson correlation analysis showed that the NLI correlated moderately with the forced expiratory volume in 1 second in subjects with COPD (r=0.490, P<0.001) and the forced vital capacity in subjects with ILD (r=0.452, P<0.001). Multivariate analysis revealed that the NLI of <70% was a significant independent predictor of mortality in subjects with COPD (hazard ratio=3.14, P=0.034) and ILD (hazard ratio=2.72, P=0.005). CONCLUSION: QCT analysis, specifically the NLI, can also be used to predict mortality in individuals with COPD and ILD.


Asunto(s)
Enfermedades Pulmonares Intersticiales , Enfermedad Pulmonar Obstructiva Crónica , Enfisema Pulmonar , Humanos , Pulmón/diagnóstico por imagen , Enfermedades Pulmonares Intersticiales/diagnóstico por imagen , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico por imagen , Enfisema Pulmonar/diagnóstico por imagen , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos
20.
New Phytol ; 235(5): 1900-1912, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35644901

RESUMEN

The strigolactone (SL) class of phytohormones shows broad chemical diversity, the functional importance of which remains to be fully elucidated, along with the enzymes responsible for the diversification of the SL structure. Here we explore the functional evolution of the highly conserved CYP711A P450 family, members of which catalyze several key monooxygenation reactions in the strigolactone pathway. Ancestral sequence reconstruction was utilized to infer ancestral CYP711A sequences based on a comprehensive set of extant CYP711 sequences. Eleven ancestral enzymes, corresponding to key points in the CYP711A phylogenetic tree, were resurrected and their activity was characterized towards the native substrate carlactone and the pure enantiomers of the synthetic strigolactone analogue, GR24. The ancestral and extant CYP711As tested accepted GR24 as a substrate and catalyzed several diversifying oxidation reactions on the structure. Evidence was obtained for functional divergence in the CYP711A family. The monocot group 3 ancestor, arising from gene duplication events within monocot grasses, showed both increased catalytic activity towards GR24 and high stereoselectivity towards the GR24 isomer resembling strigol-type SLs. These results are consistent with a role for CYP711As in strigolactone diversification in early land plants, which may have extended to the diversification of strigol-type SLs.


Asunto(s)
Duplicación de Gen , Poaceae , Compuestos Heterocíclicos con 3 Anillos , Lactonas/metabolismo , Filogenia , Reguladores del Crecimiento de las Plantas/metabolismo , Poaceae/genética , Poaceae/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...