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1.
Mol Cell ; 71(5): 718-732.e9, 2018 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-30193097

RESUMEN

Cytosolic phosphoenolpyruvate carboxykinase (PCK1) is considered a gluconeogenic enzyme; however, its metabolic functions and regulatory mechanisms beyond gluconeogenesis are poorly understood. Here, we describe that dynamic acetylation of PCK1 interconverts the enzyme between gluconeogenic and anaplerotic activities. Under high glucose, p300-dependent hyperacetylation of PCK1 did not lead to protein degradation but instead increased the ability of PCK1 to perform the anaplerotic reaction, converting phosphoenolpyruvate to oxaloacetate. Lys91 acetylation destabilizes the active site of PCK1 and favors the reverse reaction. At low energy input, we demonstrate that SIRT1 deacetylates PCK1 and fully restores the gluconeogenic ability of PCK1. Additionally, we found that GSK3ß-mediated phosphorylation of PCK1 decreases acetylation and increases ubiquitination. Biochemical evidence suggests that serine phosphorylation adjacent to Lys91 stimulates SIRT1-dependent deacetylation of PCK1. This work reveals an unexpected capacity of hyperacetylated PCK1 to promote anaplerotic activity, and the intersection of post-translational control of PCK1 involving acetylation, phosphorylation, and ubiquitination.


Asunto(s)
Gluconeogénesis/fisiología , Fosfoenolpiruvato Carboxiquinasa (GTP)/metabolismo , Acetilación , Animales , Dominio Catalítico/fisiología , Línea Celular , Línea Celular Tumoral , Femenino , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Células HEK293 , Células Hep G2 , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Procesamiento Proteico-Postraduccional/fisiología , Sirtuina 1/metabolismo , Ubiquitinación/fisiología
2.
Sex Transm Dis ; 51(6): 437-440, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38733973

RESUMEN

OBJECTIVES: Live biotherapeutic products (LBPs) containing vaginal Lactobacillus crispatus are promising adjuvant treatments to prevent recurrent bacterial vaginosis (BV) but may depend on the success of initial antibiotic treatment. METHODS: A post hoc analysis of data collected during the phase 2b LACTIN-V randomized control trial (L. crispatus CTV-05) explored the impact of clinical BV cure defined as Amsel criteria 0 of 3 (excluding pH, per 2019 Food and Drug Administration guidance) 2 days after completion of treatment with vaginal metronidazole gel on the effectiveness of an 11-week LACTIN-V dosing regimen to prevent BV recurrence by 12 and 24 weeks. RESULTS: At enrollment, 88% of participants had achieved postantibiotic clinical BV cure. The effect of LACTIN-V on BV recurrence compared with placebo differed by initial clinical BV cure status. The LACTIN-V to placebo risk ratio of BV recurrence by 12 weeks was 0.56 (95% confidence interval, 0.35-0.77) among participants with initial clinical BV cure after metronidazole treatment and 1.34 (95% confidence interval, 0.47-2.23) among participants without postantibiotic clinical BV cure. Among women receiving LACTIN-V, those who had achieved postantibiotic clinical BV cure at enrollment reached higher levels of detectable L. crispatus CTV-05 compared with women failing to achieve postantibiotic clinical BV cure. CONCLUSIONS: LACTIN-V seems to only decrease BV recurrence in women with clinical cure of BV after initial antibiotic treatment. Future trials of LBPs should consider limiting enrollment to these women.


Asunto(s)
Antibacterianos , Lactobacillus crispatus , Metronidazol , Probióticos , Vaginosis Bacteriana , Humanos , Femenino , Vaginosis Bacteriana/tratamiento farmacológico , Vaginosis Bacteriana/prevención & control , Vaginosis Bacteriana/microbiología , Metronidazol/administración & dosificación , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Adulto , Lactobacillus crispatus/fisiología , Probióticos/administración & dosificación , Resultado del Tratamiento , Recurrencia , Prevención Secundaria , Administración Intravaginal , Adulto Joven , Vagina/microbiología , Método Doble Ciego
3.
J Intern Med ; 293(4): 433-444, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36544257

RESUMEN

Bacterial vaginosis (BV) is a proinflammatory genital condition characterized by high vaginal bacterial diversity and a paucity of Lactobacillus species. BV has been linked to an elevated risk of HIV acquisition among HIV-negative women and of forward HIV transmission to male sex partners among women living with HIV (adjusted hazard ratios of 1.69 and 3.17, respectively), potentially by eliciting genital inflammation in women with BV and their male sex partners. BV is also highly prevalent among women in sub-Saharan Africa, suggesting that BV treatment may have potential as an HIV prevention strategy. BV is typically treated with antibiotics but recurrence rates are high, possibly because treatment does not directly promote Lactobacillus growth. More recently, BV treatment strategies incorporating live biotherapeutic lactobacilli have led to sustained optimization of the vaginal microbiome and a decrease in inflammatory biomarkers previously associated with HIV susceptibility. Future studies are urgently needed to evaluate BV treatment strategies that can optimize the vaginal microbiome in the long term through colonization with H2 O2 -producing vaginal lactobacilli and to assess whether vaginal microbiota optimization is able to reduce the risk of HIV transmission.


Asunto(s)
Infecciones por VIH , Microbiota , Vaginosis Bacteriana , Masculino , Femenino , Humanos , Heterosexualidad , Infecciones por VIH/prevención & control , Vagina/microbiología , Vaginosis Bacteriana/complicaciones , Vaginosis Bacteriana/microbiología , Vaginosis Bacteriana/terapia
4.
COPD ; 17(5): 509-514, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32835523

RESUMEN

Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity among miners. There is an increasing number of women in the mining industry and the differences in their risk for COPD compared to men miners are not understood. Our objective is to compare the odds for COPD between male and female miners. Using cross-sectional data from the Mining Dust in the United States (MiDUS) Cohort, that included New Mexico miners between 1989 and 2018, we compared the odds for airflow obstruction or chronic bronchitis between women and men. There were 299 women in this diverse cohort of 7,464 miners. Compared to men, female miners reported lower cumulative smoking but higher prevalence of current smoking. Multivariable analysis showed that women miners had significantly lower odds for having airflow obstruction (OR 0.40; 95% CI (0.26, 0.6)) and chronic bronchitis (OR 0.31, 95% CI (0.19, 0.53)) than men. Future studies need to determine whether this sex difference is explained by residual confounders or true biological difference.


Asunto(s)
Minería , Enfermedades Profesionales/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Adulto , Anciano , Estudios de Cohortes , Estudios Transversales , Femenino , Volumen Espiratorio Forzado , Humanos , Masculino , Persona de Mediana Edad , New Mexico , Oportunidad Relativa , Prevalencia , Distribución por Sexo , Fumar
5.
Appl Environ Microbiol ; 85(10)2019 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-30877115

RESUMEN

Plants expend significant resources to select and maintain rhizosphere communities that benefit their growth and protect them from pathogens. A better understanding of assembly and function of rhizosphere microbial communities will provide new avenues for improving crop production. Secretion of antibiotics is one means by which bacteria interact with neighboring microbes and sometimes change community composition. In our analysis of a taxonomically diverse consortium from the soybean rhizosphere, we found that Pseudomonas koreensis selectively inhibits growth of Flavobacterium johnsoniae and other members of the Bacteroidetes grown in soybean root exudate. A genetic screen in P. koreensis identified a previously uncharacterized biosynthetic gene cluster responsible for the inhibitory activity. Metabolites were isolated based on biological activity and were characterized using tandem mass spectrometry, multidimensional nuclear magnetic resonance, and Mosher ester analysis, leading to the discovery of a new family of bacterial tetrahydropyridine alkaloids, koreenceine A to D (metabolites 1 to 4). Three of these metabolites are analogs of the plant alkaloid γ-coniceine. Comparative analysis of the koreenceine cluster with the γ-coniceine pathway revealed distinct polyketide synthase routes to the defining tetrahydropyridine scaffold, suggesting convergent evolution. Koreenceine-type pathways are widely distributed among Pseudomonas species, and koreenceine C was detected in another Pseudomonas species from a distantly related cluster. This work suggests that Pseudomonas and plants convergently evolved the ability to produce similar alkaloid metabolites that can mediate interbacterial competition in the rhizosphere.IMPORTANCE The microbiomes of plants are critical to host physiology and development. Microbes are attracted to the rhizosphere due to massive secretion of plant photosynthates from roots. Microorganisms that successfully join the rhizosphere community from bulk soil have access to more abundant and diverse molecules, producing a highly competitive and selective environment. In the rhizosphere, as in other microbiomes, little is known about the genetic basis for individual species' behaviors within the community. In this study, we characterized competition between Pseudomonas koreensis and Flavobacterium johnsoniae, two common rhizosphere inhabitants. We identified a widespread gene cluster in several Pseudomonas spp. that is necessary for the production of a novel family of tetrahydropyridine alkaloids that are structural analogs of plant alkaloids. We expand the known repertoire of antibiotics produced by Pseudomonas in the rhizosphere and demonstrate the role of the metabolites in interactions with other rhizosphere bacteria.


Asunto(s)
Alcaloides/metabolismo , Flavobacterium/crecimiento & desarrollo , Pseudomonas/fisiología , Pirrolidinas/metabolismo , Rizosfera , Interacciones Microbianas , Microbiología del Suelo
6.
J Exp Biol ; 221(Pt 18)2018 09 27.
Artículo en Inglés | MEDLINE | ID: mdl-30065035

RESUMEN

Giant clams (genus Tridacna) are the largest living bivalves and, like reef-building corals, host symbiotic dinoflagellate algae (Symbiodinium) that significantly contribute to their energy budget. In turn, Symbiodinium rely on the host to supply inorganic carbon (Ci) for photosynthesis. In corals, host 'proton pump' vacuolar-type H+-ATPase (VHA) is part of a carbon-concentrating mechanism (CCM) that promotes Symbiodinium photosynthesis. Here, we report that VHA in the small giant clam (Tridacna maxima) similarly promotes Symbiodinium photosynthesis. VHA was abundantly expressed in the apical membrane of epithelial cells of T. maxima's siphonal mantle tubule system, which harbors Symbiodinium Furthermore, application of the highly specific pharmacological VHA inhibitors bafilomycin A1 and concanamycin A significantly reduced photosynthetic O2 production by ∼40%. Together with our observation that exposure to light increased holobiont aerobic metabolism ∼5-fold, and earlier estimates that translocated fixed carbon exceeds metabolic demand, we conclude that VHA activity in the siphonal mantle confers strong energetic benefits to the host clam through increased supply of Ci to algal symbionts and subsequent photosynthetic activity. The convergent role of VHA in promoting Symbiodinium photosynthesis in the giant clam siphonal mantle tubule system and coral symbiosome suggests that VHA-driven CCM is a common exaptation in marine photosymbioses that deserves further investigation in other taxa.


Asunto(s)
Proteínas Algáceas/metabolismo , Cardiidae/fisiología , Dinoflagelados/metabolismo , Fotosíntesis , Proteínas Protozoarias/metabolismo , Simbiosis/fisiología , ATPasas de Translocación de Protón Vacuolares/metabolismo , Animales , Metabolismo Energético
7.
Biol Lett ; 14(6)2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29899125

RESUMEN

The giant clam Tridacna crocea, native to Indo-Pacific coral reefs, is noted for its unique ability to bore fully into coral rock and is a major agent of reef bioerosion. However, T. crocea's mechanism of boring has remained a mystery despite decades of research. By exploiting a new, two-dimensional pH-sensing technology and manipulating clams to press their presumptive boring tissue (the pedal mantle) against pH-sensing foils, we show that this tissue lowers the pH of surfaces it contacts by greater than or equal to 2 pH units below seawater pH day and night. Acid secretion is likely mediated by vacuolar-type H+-ATPase, which we demonstrate (by immunofluorescence) is abundant in the pedal mantle outer epithelium. Our discovery of acid secretion solves this decades-old mystery and reveals that, during bioerosion, T. crocea can liberate reef constituents directly to the soluble phase, rather than producing sediment alone as earlier assumed.


Asunto(s)
Bivalvos/metabolismo , Epitelio/química , Ácidos/metabolismo , Animales , Bivalvos/química , Arrecifes de Coral , Concentración de Iones de Hidrógeno , ATPasas de Translocación de Protón/análisis
8.
BMC Cancer ; 16(1): 773, 2016 10 06.
Artículo en Inglés | MEDLINE | ID: mdl-27716204

RESUMEN

BACKGROUND: The epidermal growth factor receptor (EGFR) is frequently overexpressed in head and neck squamous cell carcinoma (HNSCC) and several other human cancers. Monoclonal antibodies, such as cetuximab that block EGFR signaling, have emerged as valuable molecular targeting agents in clinical cancer therapy. Prolonged exposure to cetuximab can result in cells acquiring resistance by a process that remains incompletely understood. METHODS: In this study, we analyzed the immediate early molecular response of cetuximab on physical interactions between EGFR and Insulin growth factor 1 like receptor (IGF-1R) in head and neck cancer cells that are resistant to cetuximab. Co-immunoprecipitation, small molecule inhibitors against phospho-Src and IGF-1R, quantitative western blot of EGFR and Src phosphorylation, cell proliferation assays were used to suggest the role of IGF-1R mediated phosphorylation of specific tyrosine Y845 on EGFR via increased heterodimerization of EGFR and IGF-1R in cetuximab resistant cells. RESULTS: Heterodimerization of EGFR with IGF-1R was increased in cetuximab resistant HNSCC cell line UMSCC6. Basal levels of phosphorylated EGFR Y845 showed significant increase in the presence of cetuximab. Surprisingly, this activated Y845 level was not inhibited in the presence of Src inhibitor PP1. Instead, inhibition of IGF-1R by picropodophyllin (PPP) reduced the EGFR Y845 levels. Taken together, these results suggest that heterodimerization of EGFR with IGF-1R can lead to increased activity of EGFR and may be an important platform for cetuximab mediated signaling in head and neck tumors that have become resistant to anti-EGFR therapy. CONCLUSIONS: EGFR-IGF-1R interaction has a functional consequence of phosphorylation of EGFR Y845 in cetuximab resistant HNSCC cells and dual targeting of EGFR and IGF-1R is a promising therapeutic strategy.


Asunto(s)
Receptores de Somatomedina/metabolismo , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Cetuximab/farmacología , Resistencia a Antineoplásicos , Receptores ErbB/metabolismo , Humanos , Fosforilación , Multimerización de Proteína , Procesamiento Proteico-Postraduccional , Receptor IGF Tipo 1
9.
J Biol Chem ; 289(21): 14941-54, 2014 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-24692551

RESUMEN

Fatty acid-binding proteins (FABPs) are a widely expressed group of calycins that play a well established role in solubilizing cellular fatty acids. Recent studies, however, have recast FABPs as active participants in vital lipid-signaling pathways. FABP5, like its family members, displays a promiscuous ligand binding profile, capable of interacting with numerous long chain fatty acids of varying degrees of saturation. Certain "activating" fatty acids induce the protein's cytoplasmic to nuclear translocation, stimulating PPARß/δ transactivation; however, the rules that govern this process remain unknown. Using a range of structural and biochemical techniques, we show that both linoleic and arachidonic acid elicit FABP5's translocation by permitting allosteric communication between the ligand-sensing ß2 loop and a tertiary nuclear localization signal within the α-helical cap of the protein. Furthermore, we show that more saturated, nonactivating fatty acids inhibit nuclear localization signal formation by destabilizing this activation loop, thus implicating FABP5 specifically in cis-bonded, polyunsaturated fatty acid signaling.


Asunto(s)
Proteínas de Unión a Ácidos Grasos/metabolismo , Ácidos Grasos/metabolismo , PPAR gamma/metabolismo , PPAR-beta/metabolismo , Animales , Ácido Araquidónico/química , Ácido Araquidónico/metabolismo , Ácido Araquidónico/farmacología , Sitios de Unión , Células COS , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Chlorocebus aethiops , Citoplasma/efectos de los fármacos , Citoplasma/metabolismo , Proteínas de Unión a Ácidos Grasos/química , Proteínas de Unión a Ácidos Grasos/genética , Ácidos Grasos/química , Ácidos Grasos/farmacología , Humanos , Ligandos , Ácido Linoleico/química , Ácido Linoleico/metabolismo , Ácido Linoleico/farmacología , Células MCF-7 , Modelos Moleculares , Estructura Molecular , Mutación , Señales de Localización Nuclear/química , Señales de Localización Nuclear/metabolismo , PPAR gamma/genética , PPAR-beta/genética , Unión Proteica , Estructura Secundaria de Proteína , Estructura Terciaria de Proteína , Transporte de Proteínas/efectos de los fármacos , Activación Transcripcional/efectos de los fármacos
10.
Microbiome ; 12(1): 110, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38907268

RESUMEN

BACKGROUND: Bacterial vaginosis (BV) increases HIV acquisition risk, potentially by eliciting genital inflammation. After BV treatment, the vaginal administration of LACTIN-V, a live biotherapeutic containing the Lactobacillus crispatus strain CTV-05, reduced BV recurrence and vaginal inflammation; however, 3 months after product cessation, CTV-05 colonization was only sustained in 48% of participants. RESULTS: This nested sub-study in 32 participants receiving LACTIN-V finds that 72% (23/32) demonstrate clinically relevant colonization (CTV-05 absolute abundance > 106 CFU/mL) during at least one visit while 28% (9/32) of women demonstrate colonization resistance, even during product administration. Immediately prior to LACTIN-V administration, the colonization-resistant group exhibited elevated vaginal microbiota diversity. During LACTIN-V administration, colonization resistance was associated with elevated vaginal markers of epithelial disruption and reduced chemokines, possibly due to elevated absolute abundance of BV-associated species and reduced L. crispatus. Colonization permissive women were stratified into sustained and transient colonization groups (31% and 41% of participants, respectively) based on CTV-05 colonization after cessation of product administration. These groups also exhibited distinct genital immune profiles during LACTIN-V administration. CONCLUSIONS: The genital immune impact of LACTIN-V may be contingent on the CTV-05 colonization phenotype, which is in turn partially dependent on the success of BV clearance prior to LACTIN-V administration.


Asunto(s)
Lactobacillus crispatus , Vagina , Vaginosis Bacteriana , Humanos , Femenino , Vaginosis Bacteriana/microbiología , Vaginosis Bacteriana/inmunología , Vagina/microbiología , Adulto , Probióticos/administración & dosificación , Administración Intravaginal , Microbiota , Adulto Joven , Fenotipo
11.
Microbiol Spectr ; : e0350123, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38912808

RESUMEN

Vaginal colonization by fungi may elicit genital inflammation and enhance the risk of adverse reproductive health outcomes, such as HIV acquisition. Cross-sectional studies have linked fungi with an absence of bacterial vaginosis (BV), but it is unclear whether shifts in vaginal bacteria alter the abundance of vaginal fungi. Vaginal swabs collected following topical metronidazole treatment for BV during the phase 2b, placebo-controlled trial of LACTIN-V, a Lactobacillus crispatus-based live biotherapeutic, were assayed with semi-quantitative PCR for the relative quantitation of fungi and key bacterial species and multiplex immunoassay for immune factors. Vaginal fungi increased immediately following metronidazole treatment for BV (adjusted P = 0.0006), with most of this increase attributable to Candida albicans. Vaginal fungi were independently linked to elevated levels of the proinflammatory cytokine interleukin (IL) 17A, although this association did not remain significant after correcting for multiple comparisons. Fungal relative abundance by semi-quantitative PCR returned to baseline levels within 1 month of metronidazole treatment and was not affected by LACTIN-V or placebo administration. Fungal abundance was positively associated with Lactobacillus species, negatively associated with BV-associated bacteria, and positively associated with a variety of proinflammatory cytokines and chemokines, including IL-17A, during and after study product administration. Antibiotic treatment for BV resulted in a transient expanded abundance of vaginal fungi in a subset of women which was unaffected by subsequent administration of LACTIN-V. Vaginal fungi were positively associated with Lactobacillus species and IL-17A and negatively associated with BV-associated bacteria; these associations were most pronounced in the longer-term outcomes.IMPORTANCEVaginal colonization by fungi can enhance the risk of adverse reproductive health outcomes and HIV acquisition, potentially by eliciting genital mucosal inflammation. We show that standard antibiotic treatment for bacterial vaginosis (BV) results in a transient increase in the absolute abundance of vaginal fungi, most of which was identified as Candida albicans. Vaginal fungi were positively associated with proinflammatory immune factors and negatively associated with BV-associated bacteria. These findings improve our understanding of how shifts in the bacterial composition of the vaginal microbiota may enhance proliferation by proinflammatory vaginal fungi, which may have important implications for risk of adverse reproductive health outcomes among women.

12.
Phys Chem Chem Phys ; 15(7): 2298-308, 2013 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-23295732

RESUMEN

A novel approach, called isothermal isotope exchange (IIE), was applied to varying A- and B-site lanthanum manganites, ferrites, and cobaltites in the perovskite crystal structure in order to extract accurate surface exchange coefficients (k*). Pure electronic conductors revealed temperature dependent isotope exchange, while for mixed ionic and electronic conductors (MIEC) the extent of exchange was independent of temperature. MIEC materials have higher k* values than pure electronic conductors in the temperature range from 500-850 °C, demonstrating the importance of both electronic species and oxygen vacancies being present for surface exchange. Strontium doped perovskites exhibited opposite temperature dependencies to parent materials. Some perovskites exhibited an apparent negative activation energy for k*, the behavior of which is explained by a precursor-mediated mechanism for dissociative adsorption. The results have significant implications for the improvement of the oxygen reduction reaction for fuel cells, metal-air batteries, and numerous other energy technologies.

13.
bioRxiv ; 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38106163

RESUMEN

Dietary protein and essential amino acid (EAA) restriction promotes favorable metabolic reprogramming, ultimately resulting in improvements to both health and lifespan. However, as individual EAAs have distinct catabolites and engage diverse downstream signaling pathways, it remains unclear to what extent shared or AA-specific molecular mechanisms promote diet-associated phenotypes. Here, we investigated the physiological and molecular effects of restricting either dietary methionine, leucine, or isoleucine (Met-R, Leu-R, and Ile-R) for 3 weeks in C57BL/6J male mice. While all 3 AA-depleted diets promoted fat and lean mass loss and slightly improved glucose tolerance, the molecular responses were more diverse; while hepatic metabolites altered by Met-R and Leu-R were highly similar, Ile-R led to dramatic changes in metabolites, including a 3-fold reduction in the oncometabolite 2-hydroxyglutarate. Pathways regulated in an EAA-specific manner included glycolysis, the pentose phosphate pathway (PPP), nucleotide metabolism, the TCA cycle and amino acid metabolism. Transcriptiome analysis and global profiling of histone post-translational modifications (PTMs) revealed different patterns of responses to each diet, although Met-R and Leu-R again shared similar transcriptional responses. While the pattern of global histone PTMs were largely unique for each dietary intervention, Met-R and Ile-R had similar changes in histone-3 methylation/acetylation PTMs at lysine-9. Few similarities were observed between the physiological or molecular responses to EAA restriction and treatment with rapamycin, an inhibitor of the mTORC1 AA-responsive protein kinase, indicating the response to EAA restriction may be largely independent of mTORC1. Together, these results demonstrate that dietary restriction of individual EAAs has unique, EAA-specific effects on the hepatic metabolome, epigenome, and transcriptome, and suggests that the specific EAAs present in dietary protein may play a key role at regulating health at the molecular level.

14.
Open Forum Infect Dis ; 10(1): ofad007, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36726539

RESUMEN

Background: Bacterial vaginosis (BV) is a proinflammatory genital condition associated with adverse reproductive health outcomes, including increased HIV incidence. However, BV recurrence rates are high after standard antibiotic treatment. While the composition of the vaginal microbiota before BV treatment may be linked to BV recurrence, it is unclear whether the preceding genital immune milieu is predictive of treatment success. Methods: Here we assessed whether baseline vaginal soluble immune factors or the composition of the vaginal microbiota predicted treatment success 1 month after metronidazole treatment in 2 separate cohorts of women with BV, 1 in the United States and 1 in Kenya; samples within 48 hours of BV treatment were also available for the US cohort. Results: Neither soluble immune factors nor the composition of the vaginal microbiota before BV treatment was associated with treatment response in either cohort. In the US cohort, although the absolute abundances of key vaginal bacterial taxa pretreatment were not associated with treatment response, participants with sustained BV clearance had a more pronounced reduction in the absolute abundance of Gardnerella vaginalis immediately after treatment. Conclusions: Pretreatment immune and microbial parameters were not predictive of BV treatment success in these clinical cohorts.

15.
Am J Reprod Immunol ; 89(3): e13674, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36593681

RESUMEN

PROBLEM: The genital epithelial barrier is a crucial first line of defence against HIV, and epithelial disruption may enhance HIV susceptibility. Assessment of genital epithelial integrity requires biopsies, but their collection is not practical in many research settings. A validated biomarker of genital epithelial barrier integrity would therefore be useful. The purpose of this study was to evaluate soluble E-cadherin (sE-cad) as a marker of genital epithelial disruption. METHOD OF STUDY: Using in vitro models of endocervical and foreskin epithelial cells, we assessed changes in sE-cad, IL-6, IL-1ß, and IL-1α levels following mechanical disruption. We also assessed changes in sE-cad levels in vivo in cervicovaginal secretions after epithelial disruption by endocervical cytobrush sampling in Canadian women, and assessed the relationship between levels of sE-cad in coronal sulcus swabs to membrane-bound E-cadherin in the overlying foreskin tissue in Ugandan men. RESULTS: sE-cad levels immediately increased after in vitro epithelial physical disruption with the degree of elevation dependent on the extent of disruption, as did levels of IL-1ß and IL-1α; this was followed by a delayed increase in IL-6 levels. In vivo results confirmed that sE-cad levels in cervicovaginal secretions were elevated 6 h after cytobrush sampling when compared to baseline. Furthermore, levels of sE-cad in the prepuce were inversely correlated with the amount of membrane-bound E-cadherin of overlying tissue. CONCLUSION: Our results validate the use of sE-cad as a marker of epithelial disruption and demonstrate that the processes of physical disruption and inflammation in the genital tract are strongly intertwined.


Asunto(s)
Cadherinas , Infecciones por VIH , Masculino , Humanos , Femenino , Interleucina-6 , Canadá , Cuello del Útero
16.
Nat Commun ; 14(1): 3039, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37264002

RESUMEN

Coral reefs are among the most diverse ecosystems on Earth. They support high biodiversity of multicellular organisms that strongly rely on associated microorganisms for health and nutrition. However, the extent of the coral reef microbiome diversity and its distribution at the oceanic basin-scale remains to be explored. Here, we systematically sampled 3 coral morphotypes, 2 fish species, and planktonic communities in 99 reefs from 32 islands across the Pacific Ocean, to assess reef microbiome composition and biogeography. We show a very large richness of reef microorganisms compared to other environments, which extrapolated to all fishes and corals of the Pacific, approximates the current estimated total prokaryotic diversity for the entire Earth. Microbial communities vary among and within the 3 animal biomes (coral, fish, plankton), and geographically. For corals, the cross-ocean patterns of diversity are different from those known for other multicellular organisms. Within each coral morphotype, community composition is always determined by geographic distance first, both at the island and across ocean scale, and then by environment. Our unprecedented sampling effort of coral reef microbiomes, as part of the Tara Pacific expedition, provides new insight into the global microbial diversity, the factors driving their distribution, and the biocomplexity of reef ecosystems.


Asunto(s)
Antozoos , Microbiota , Animales , Arrecifes de Coral , Océano Pacífico , Biodiversidad , Peces , Plancton
17.
Nat Commun ; 14(1): 3037, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37264015

RESUMEN

Health and resilience of the coral holobiont depend on diverse bacterial communities often dominated by key marine symbionts of the Endozoicomonadaceae family. The factors controlling their distribution and their functional diversity remain, however, poorly known. Here, we study the ecology of Endozoicomonadaceae at an ocean basin-scale by sampling specimens from three coral genera (Pocillopora, Porites, Millepora) on 99 reefs from 32 islands across the Pacific Ocean. The analysis of 2447 metabarcoding and 270 metagenomic samples reveals that each coral genus harbored a distinct new species of Endozoicomonadaceae. These species are composed of nine lineages that have distinct biogeographic patterns. The most common one, found in Pocillopora, appears to be a globally distributed symbiont with distinct metabolic capabilities, including the synthesis of amino acids and vitamins not produced by the host. The other lineages are structured partly by the host genetic lineage in Pocillopora and mainly by the geographic location in Porites. Millepora is more rarely associated to Endozoicomonadaceae. Our results show that different coral genera exhibit distinct strategies of host-Endozoicomonadaceae associations that are defined at the bacteria lineage level.


Asunto(s)
Antozoos , Gammaproteobacteria , Animales , Antozoos/microbiología , Océano Pacífico , Ecología , Bacterias , Arrecifes de Coral
18.
Nat Commun ; 14(1): 3056, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37264036

RESUMEN

Heat waves are causing declines in coral reefs globally. Coral thermal responses depend on multiple, interacting drivers, such as past thermal exposure, endosymbiont community composition, and host genotype. This makes the understanding of their relative roles in adaptive and/or plastic responses crucial for anticipating impacts of future warming. Here, we extracted DNA and RNA from 102 Pocillopora colonies collected from 32 sites on 11 islands across the Pacific Ocean to characterize host-photosymbiont fidelity and to investigate patterns of gene expression across a historical thermal gradient. We report high host-photosymbiont fidelity and show that coral and microalgal gene expression respond to different drivers. Differences in photosymbiotic association had only weak impacts on host gene expression, which was more strongly correlated with the historical thermal environment, whereas, photosymbiont gene expression was largely determined by microalgal lineage. Overall, our results reveal a three-tiered strategy of thermal acclimatization in Pocillopora underpinned by host-photosymbiont specificity, host transcriptomic plasticity, and differential photosymbiotic association under extreme warming.


Asunto(s)
Antozoos , Transcriptoma , Animales , Océano Pacífico , Transcriptoma/genética , Antozoos/genética , Aclimatación/genética , Arrecifes de Coral
19.
Nat Commun ; 14(1): 3038, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37263999

RESUMEN

Telomeres are environment-sensitive regulators of health and aging. Here,we present telomere DNA length analysis of two reef-building coral genera revealing that the long- and short-term water thermal regime is a key driver of between-colony variation across the Pacific Ocean. Notably, there are differences between the two studied genera. The telomere DNA lengths of the short-lived, more stress-sensitive Pocillopora spp. colonies were largely determined by seasonal temperature variation, whereas those of the long-lived, more stress-resistant Porites spp. colonies were insensitive to seasonal patterns, but rather influenced by past thermal anomalies. These results reveal marked differences in telomere DNA length regulation between two evolutionary distant coral genera exhibiting specific life-history traits. We propose that environmentally regulated mechanisms of telomere maintenance are linked to organismal performances, a matter of paramount importance considering the effects of climate change on health.


Asunto(s)
Antozoos , Animales , Antozoos/genética , Arrecifes de Coral , Temperatura , Estaciones del Año , ADN/genética
20.
Genome Biol ; 24(1): 123, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37264421

RESUMEN

BACKGROUND: Over the last decade, several coral genomes have been sequenced allowing a better understanding of these symbiotic organisms threatened by climate change. Scleractinian corals are reef builders and are central to coral reef ecosystems, providing habitat to a great diversity of species. RESULTS: In the frame of the Tara Pacific expedition, we assemble two coral genomes, Porites lobata and Pocillopora cf. effusa, with vastly improved contiguity that allows us to study the functional organization of these genomes. We annotate their gene catalog and report a relatively higher gene number than that found in other public coral genome sequences, 43,000 and 32,000 genes, respectively. This finding is explained by a high number of tandemly duplicated genes, accounting for almost a third of the predicted genes. We show that these duplicated genes originate from multiple and distinct duplication events throughout the coral lineage. They contribute to the amplification of gene families, mostly related to the immune system and disease resistance, which we suggest to be functionally linked to coral host resilience. CONCLUSIONS: At large, we show the importance of duplicated genes to inform the biology of reef-building corals and provide novel avenues to understand and screen for differences in stress resilience.


Asunto(s)
Antozoos , Animales , Antozoos/genética , Ecosistema , Arrecifes de Coral
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