Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 238
Filtrar
Más filtros

Tipo del documento
Intervalo de año de publicación
1.
Proc Natl Acad Sci U S A ; 120(24): e2221691120, 2023 06 13.
Artículo en Inglés | MEDLINE | ID: mdl-37276393

RESUMEN

The idea that changing environmental conditions drive adaptive evolution is a pillar of evolutionary ecology. But, the opposite-that adaptive evolution alters ecological processes-has received far less attention yet is critical for eco-evolutionary dynamics. We assessed the ecological impact of divergent values in a key adaptive trait using 16 populations of the brown anole lizard (Anolis sagrei). Mirroring natural variation, we established islands with short- or long-limbed lizards at both low and high densities. We then monitored changes in lower trophic levels, finding that on islands with a high density of short-limbed lizards, web-spider densities decreased and plants grew more via an indirect positive effect, likely through an herbivore-mediated trophic cascade. Our experiment provides strong support for evolution-to-ecology connections in nature, likely closing an otherwise well-characterized eco-evolutionary feedback loop.


Asunto(s)
Cadena Alimentaria , Lagartos , Animales , Herbivoria , Fenotipo , Estado Nutricional , Evolución Biológica
2.
Langmuir ; 40(22): 11775-11784, 2024 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-38769025

RESUMEN

The preparation of multifunctional nanomaterials based on inorganic nanoparticles with organic materials has emerged as a promising strategy for the development of new nanomedicines for in vitro and in vivo biomedical applications. Here, we synthesized pH-responsive hybrid inorganic micelles by combining a novel pH-responsive amphiphilic molecule with hydrophobic payloads. This amphiphile was synthesized in a one-pot reaction and self-assembled readily into micelles under acidic pH conditions. In the presence of hydrophobic NP payloads such as AuNPs or IONPs, the amphiphile self-organized around them through hydrophobic interactions, resulting in the formation of colloidally stable hybrid micelles. The size of the hydrophobic NPs determined the pH-response of the inorganic hybrid micelles, which is tuned from pH 7 to 11 for our pH-responsive amphiphilic molecule. This achievement represents a novel approach for the synthesis of tunable pH-responsive hybrid micelles based on inorganic NPs for biomedical imaging, hyperthermia treatment, and also drug delivery nanosystems.


Asunto(s)
Oro , Nanopartículas del Metal , Micelas , Oro/química , Concentración de Iones de Hidrógeno , Nanopartículas del Metal/química , Compuestos Férricos/química , Interacciones Hidrofóbicas e Hidrofílicas , Tamaño de la Partícula
3.
Biol Lett ; 20(2): 20230419, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38320619

RESUMEN

Elucidating the selective forces shaping the diversity of vertebrate brains continues to be a major area of inquiry, particularly as it relates to cognition. Historically brain evolution was interpreted through the lens of relative brain size; however, recent evidence has challenged this approach. Investigating neuroanatomy at a finer scale, such as neuron number, can provide new insights into the forces shaping brain evolution in the context of information processing capacity. Ecological factors, such as the complexity of a species' habitat, place demands on cognition that could shape neuroanatomy. In this study, we investigate the relationship between neuron number and habitat complexity in three brain regions across six closely related anole species from Puerto Rico. After controlling for brain mass, we found that the number of neurons increased with habitat complexity across species in the telencephalon and 'rest of the brain,' but not in the cerebellum. Our results demonstrate that habitat complexity has shaped neuroanatomy in the Puerto Rican anole radiation and provide further evidence of the role of habitat complexity in vertebrate brain evolution.


Asunto(s)
Evolución Biológica , Lagartos , Animales , Encéfalo/anatomía & histología , Encéfalo/fisiología , Ecosistema , Lagartos/fisiología , Neuronas , Puerto Rico
4.
Mol Ecol ; 32(22): 6000-6017, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37861454

RESUMEN

Hybridization facilitates recombination between divergent genetic lineages and can be shaped by both neutral and selective processes. Upon hybridization, loci with no net fitness effects introgress randomly from parental species into the genomes of hybrid individuals. Conversely, alleles from one parental species at some loci may provide a selective advantage to hybrids, resulting in patterns of introgression that do not conform to random expectations. We investigated genomic patterns of differential introgression in natural hybrids of two species of Caribbean anoles, Anolis pulchellus and A. krugi in Puerto Rico. Hybrids exhibit A. pulchellus phenotypes but possess A. krugi mitochondrial DNA, originated from multiple, independent hybridization events, and appear to have replaced pure A. pulchellus across a large area in western Puerto Rico. Combining genome-wide SNP datasets with bioinformatic methods to identify signals of differential introgression in hybrids, we demonstrate that the genomes of hybrids are dominated by pulchellus-derived alleles and show only 10%-20% A. krugi ancestry. The majority of A. krugi loci in hybrids exhibit a signal of non-random differential introgression and include loci linked to genes involved in development and immune function. Three of these genes (delta like canonical notch ligand 1, jagged1 and notch receptor 1) affect cell differentiation and growth and interact with mitochondrial function. Our results suggest that differential non-random introgression for a subset of loci may be driven by selection favouring the inheritance of compatible mitochondrial and nuclear-encoded genes in hybrids.


Asunto(s)
Genoma , Mitocondrias , Humanos , Mitocondrias/genética , Hibridación Genética , ADN Mitocondrial/genética , Puerto Rico
5.
Immun Ageing ; 20(1): 9, 2023 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-36879319

RESUMEN

BACKGROUND: Older people achieve lower levels of antibody titers than younger populations after Covid-19 vaccination and show a marked waning humoral immunity over time, likely due to the senescence of the immune system. Nevertheless, age-related predictive factors of the waning humoral immune response to the vaccine have been scarcely explored. In a cohort of residents and healthcare workers from a nursing home that had received two doses of the BNT162b2 vaccine, we measured specific anti-S antibodies one (T1), four (T4), and eight (T8) months after receiving the second dose. Thymic-related functional markers, including thymic output, relative telomere length, and plasma thymosin-α1 levels, as well as immune cellular subsets, and biochemical and inflammatory biomarkers, were determined at T1, and tested for their associations with the magnitude of the vaccine response (T1) and the durability of such response both, at the short- (T1-T4) and the long-term (T1-T8). We aimed to identify age-related factors potentially associated with the magnitude and persistence of specific anti-S immunoglobulin G (IgG)-antibodies after COVID-19 vaccination in older people. RESULTS: Participants (100% men, n = 98), were subdivided into three groups: young (< 50 years-old), middle-age (50-65 years-old), and older (≥65 years-old). Older participants achieved lower antibody titers at T1 and experienced higher decreases in both the short- and long-term. In the entire cohort, while the magnitude of the initial response was mainly associated with the levels of homocysteine [ß (95% CI); - 0.155 (- 0.241 to - 0.068); p = 0.001], the durability of such response at both, the short-term and the long-term were predicted by the levels of thymosin-α1 [- 0.168 (- 0.305 to - 0.031); p = 0.017, and - 0.123 (- 0.212 to - 0.034); p = 0.008, respectively]. CONCLUSIONS: Higher plasma levels of thymosin-α1 were associated with a lower waning of anti-S IgG antibodies along the time. Our results suggest that plasma levels of thymosin-α1 could be used as a biomarker for predicting the durability of the responses after COVID-19 vaccination, possibly allowing to personalize the administration of vaccine boosters.

6.
Am Nat ; 200(2): 236-249, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35905402

RESUMEN

AbstractAnimal signal colors evolve to efficiently stimulate conspecific visual systems. The sensory drive hypothesis proposes that species differences in habitat light conditions favor the evolution of color diversity. The strongest support comes from aquatic systems, while terrestrial systems offer fewer convincing examples. Anolis lizards occupy diverse habitats and signal with a colorful dewlap. Dewlap visibility depends on perceived chromatic contrast with the background. Visual system modeling has shown that red dewlaps are most visible in most habitat types. However, a majority of species possess white or yellow dewlaps. In a recent behavioral study, we showed that low light conditions can sometimes make yellow and white colors more visible by altering chromatic contrast perception with the background. Using 17 Caribbean Anolis species, we showed that cut-on wavelength, a measure of dewlap color in a white to red continuum, correlates with habitat light intensity. Pairwise comparisons revealed that red dewlaps are most visible in bright habitats, whereas yellow and white are more visible in darker habitats. We conclude that sensory drive has contributed to the evolution of dewlap color differences through the interactive effects of total habitat light intensity and chromatic contrast perception and may provide a mechanism for speciation among anoles.


Asunto(s)
Lagartos , Animales , Ecosistema , Luz
7.
J Phys Chem A ; 126(51): 9605-9617, 2022 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-36524393

RESUMEN

The growing interest in multifunctional nano-objects based on polymers and magnetic nanoparticles for biomedical applications motivated us to develop a scale-up protocol to increase the yield of polymeric magnetic nanobeads while aiming at keeping the structural features at optimal conditions. The protocol was applied to two different types of magnetic ferrite nanoparticles: the Mn-ferrite selected for their properties as contrast agents in magnetic resonance imaging and iron oxide nanostar shaped nanoparticles chosen for their heat performance in magnetic hyperthermia. At the same time, some experiments on surface functionalization of nanobeads with amino modified polyethyelene glycol (PEG) molecules have provided further insight into the formation mechanism of magnetic nanobeads and the need to cross-link the polymer shell to improve the stability of the beads, making them more suitable for further manipulation and use. The present work summarizes the most important parameters required to be controlled for the upscaling of nanobead synthesis in a bench protocol and proposes an alternative cross-linking strategy based on prefunctionalization of the polymer prior to the nanobead formation as a key parameter to improve the nanobead structural stability in solutions at different pHs and during surface functionalization.


Asunto(s)
Nanopartículas , Polímeros , Polímeros/química , Compuestos Férricos/química , Nanopartículas/química , Imagen por Resonancia Magnética/métodos
8.
J Therm Biol ; 106: 103228, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35636896

RESUMEN

Small differences in physiological responses are known to influence demographic rates such as survival. We tested for differences in the physiological acclimation responses of two closely-related salamander species that often co-occur, Ambystoma maculatum and A. opacum. Specifically, we measured changes in critical thermal maxima (CTmax), standard metabolic rates (SMRs), and respiratory surface area water loss (RSAWL) following exposure to three temperature treatments under laboratory conditions. While the magnitude of RSAWL and CTmax acclimation responses to warming did not differ between the study species, SMR was maintained across acclimation temperatures among A. maculatum, but declined among A. opacum acclimated to warmer temperatures. Metabolic compensation may facilitate maintained A. maculatum activity levels during warm periods following the relatively cool spring breeding season. In contrast, metabolic suppression may allow A. opacum to conserve energy when exposed to surface conditions during fall breeding and nest guarding. We simulated how these different SMR responses would likely alter post-metamorphic survival in our study species using previously collected data representing six weeks under relatively warm seminatural conditions. Our simulation indicated that, following warming and under identical study conditions, metabolic compensation may allow juvenile A. maculatum to maintain survival likelihoods, whereas metabolic depression may cause juvenile A. opacum to experience increased survivorship. These findings underscore that comparable physiological responses among ecologically similar, sympatric species cannot be assumed. Further, results of this study suggest that metabolic responses may play an important role in amphibian species persistence as temperatures increase due to habitat modification and climate change.


Asunto(s)
Aclimatación , Urodelos , Aclimatación/fisiología , Adaptación Fisiológica , Animales , Cambio Climático , Temperatura
9.
Int J Mol Sci ; 23(4)2022 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-35216318

RESUMEN

A significant proportion of people living with HIV (PLHIV) who successfully achieve virological suppression fail to recover CD4+ T-cell counts. Since adipose tissue has been discovered as a key immune organ, this study aimed to assess the role of adipokines in the HIV immunodiscordant response. This is a multicenter prospective study including 221 PLHIV starting the first antiretroviral therapy (ART) and classified according to baseline CD4+ T-cell counts/µL (controls > 200 cells/µL and cases ≤ 200 cells/µL). Immune failure recovery was considered when cases did not reach more than 250 CD4+ T cells/µL at 144 weeks (immunological nonresponders, INR). Circulating adipokine concentrations were longitudinally measured using enzyme-linked immunosorbent assays. At baseline, apelin receptor (APLNR) and zinc-alpha-2-glycoprotein (ZAG) concentrations were significantly lower in INRs than in immunological responders (p = 0.043 and p = 0.034), and they remained lower during all ART follow-up visits (p = 0.044 and p = 0.028 for APLNR, p = 0.038 and p = 0.010 for ZAG, at 48 and 144 weeks, respectively). ZAG levels positively correlated with retinol-binding protein 4 (RBP4) levels (p < 0.01), and low circulating RBP4 concentrations were related to a low CD4+ T-cell gain (p = 0.018 and p = 0.039 at 48 and 144 weeks, respectively). Multiple regression adjusted for clinical variables and adipokine concentrations confirmed both low APLNR and RBP4 as independent predictors for CD4+ T cells at 144 weeks (p < 0.001). In conclusion, low APLNR and RBP4 concentrations were associated with poor immune recovery in treated PLHIV and could be considered predictive biomarkers of a discordant immunological response.


Asunto(s)
Adipoquinas/metabolismo , Receptores de Apelina/metabolismo , Biomarcadores/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Infecciones por VIH/metabolismo , Proteínas Plasmáticas de Unión al Retinol/metabolismo , Adipoquinas/inmunología , Adulto , Terapia Antirretroviral Altamente Activa/métodos , Receptores de Apelina/inmunología , Recuento de Linfocito CD4/métodos , Linfocitos T CD4-Positivos/inmunología , Femenino , Infecciones por VIH/inmunología , VIH-1/inmunología , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Proteínas Plasmáticas de Unión al Retinol/inmunología , Carga Viral/fisiología
10.
Soft Matter ; 17(46): 10580, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34806102

RESUMEN

Correction for 'Clickable iron oxide NPs based on catechol derived ligands: synthesis and characterization' by Esther Pozo-Torres et al., Soft Matter, 2020, 16, 3257-3266, DOI: 10.1039/C9SM02512J.

11.
Soft Matter ; 16(13): 3257-3266, 2020 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-32163076

RESUMEN

Clickable magnetic nanoparticles have attracted great attention as potential nanoplatforms for biomedical applications because of the high functionalization efficiency of their surfaces with biomolecules, which facilitates their bio-compatibilization. However, the design and synthesis of clickable NPs is still challenging because of the complexity of the chemistry on the magnetic NP surface, thus robust methods that improve the ligand synthesis and the transfer of magnetic NPs in physiological media being in high-demand. In this work, we developed a versatile and enhanced synthetic route to fabricate potentially clickable IONPs of interest in nanomedicine. Catechol anchor ligands with different stereo-electronic features were synthetized from a hetero bi-functional PEG spacer backbone. The resulting catechol ligands transferred in good yields and high stability to magnetic NPs by an improved energetic ligand exchange method that combines sonication and high temperature. The azido functionalized IONPs exhibited excellent characteristics as T2 MRI contrast agents with low cytotoxicity, making these clickable magnetic NPs promising precursors for nanomedicines.


Asunto(s)
Catecoles/química , Química Clic , Compuestos Férricos/química , Nanopartículas del Metal/química , Catecoles/síntesis química , Ligandos
12.
Oecologia ; 194(3): 371-382, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-33057838

RESUMEN

Population persistence is informed by the ability of individuals to cope with local abiotic conditions, which is commonly mediated by physiological traits. Among biphasic amphibians, juveniles-which are infrequently studied but play a key role in amphibian population dynamics-are the first life stage to experience terrestrial conditions following the aquatic larval stage. To illuminate phenotypic variation that may allow juveniles to survive the physiological challenges presented by this transition, we examined respiratory surface area water loss (RSAWL) and standard metabolic rates (SMR) among juveniles reared under common larval conditions for five salamander species (Ambystoma annulatum, A. maculatum, A. opacum, A. talpoideum, and A. texanum) collected across ~ 200 km of latitude in Missouri, USA. We found that SMR described 34% of variation in RSAWL, suggesting that physiological water conservation may be limited by energetic regulation among these species, and vice versa. On average, species differed in juvenile SMR and residual values of RSAWL (corrected for body size/shape) by 0.04 mL [Formula: see text] and 0.16, respectively, possibly because of distinct species ecologies. For example, A. annulatum had higher SMR and RSAWL compared to broadly distributed study species, potentially associated with a relatively narrow range of environmental conditions experienced across the small geographic distribution of A. annulatum. Latitude correlated negatively with temperature and precipitation, and positively with RSAWL, suggesting that variation in RSAWL may be adaptive to local conditions. We provide evidence that species differences likely have a genetic basis, reflecting selection favoring species divergence to effectively use distinct microhabitats.


Asunto(s)
Anfibios , Agua , Ambystoma , Animales , Humanos , Missouri , Urodelos
13.
J Infect Dis ; 219(6): 867-876, 2019 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-30312441

RESUMEN

BACKGROUND: Elite controllers (ECs) spontaneously control plasma human immunodeficiency virus type 1 (HIV-1) RNA without antiretroviral therapy. However, 25% lose virological control over time. The aim of this work was to study the proteomic profile that preceded this loss of virological control to identify potential biomarkers. METHODS: Plasma samples from ECs who spontaneously lost virological control (transient controllers [TCs]), at 2 years and 1 year before the loss of control, were compared with a control group of ECs who persistently maintained virological control during the same follow-up period (persistent controllers [PCs]). Comparative plasma shotgun proteomics was performed with tandem mass tag (TMT) isobaric tag labeling and nanoflow liquid chromatography coupled to Orbitrap mass spectrometry. RESULTS: Eighteen proteins exhibited differences comparing PC and preloss TC timepoints. These proteins were involved in proinflammatory mechanisms, and some of them play a role in HIV-1 replication and pathogenesis and interact with structural viral proteins. Coagulation factor XI, α-1-antichymotrypsin, ficolin-2, 14-3-3 protein, and galectin-3-binding protein were considered potential biomarkers. CONCLUSIONS: The proteomic signature associated with the spontaneous loss of virological control was characterized by higher levels of inflammation, transendothelial migration, and coagulation. Galectin-3 binding protein could be considered as potential biomarker for the prediction of virological progression and as therapeutic target in ECs.


Asunto(s)
Infecciones por VIH/inmunología , Proteoma/análisis , Adulto , Biomarcadores/sangre , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/virología , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/virología , VIH-1/inmunología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Carga Viral , Replicación Viral
14.
J Virol ; 92(5)2018 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-29212942

RESUMEN

HIV-1 elite controllers (EC) maintain undetectable viral loads (VL) in the absence of antiretroviral treatment. However, these subjects have heterogeneous clinical outcomes, including a proportion that loses HIV-1 control over time. In this work, we compared, in a longitudinal design, transient EC, analyzed before and after the loss of virological control, with persistent EC. The aim was to identify factors leading to the loss of natural virological control of HIV-1 infection with a longitudinal retrospective study design. Gag-specific T-cell responses were assessed by in vitro intracellular polycytokine production quantified by flow cytometry. Viral diversity determinations and sequence dating were performed in proviral DNA by PCR amplification at limiting dilution of env and gag genes. The expression profile of 70 serum cytokines and chemokines was assessed by multiplex immunoassays. We identified transient EC as subjects with low Gag-specific T-cell polyfunctionality, high viral diversity, and high proinflammatory cytokine levels before the loss of control. Gag-specific T-cell polyfunctionality was inversely associated with viral diversity in transient controllers before the loss of control (r = -0.8; P = 0.02). RANTES was a potential biomarker of transient control. This study identified virological and immunological factors, including inflammatory biomarkers associated with two different phenotypes within EC. These results may allow a more accurate definition of EC, which could help in better clinical management of these individuals and in the development of future curative approaches.IMPORTANCE There is a rare group of HIV-infected patients who have the extraordinary capacity to maintain undetectable viral load levels in the absence of antiretroviral treatment, the so-called HIV-1 elite controllers (EC). However, there is a proportion within these subjects that eventually loses this capability. In this work, we found differences in virological and immune factors, including soluble inflammatory biomarkers, between subjects with persistent control of viral replication and EC that will lose virological control. The identification of these factors could be a key point for a right medical care of those EC who are going to lose natural control of viral replication and for the design of future immunotherapeutic strategies using as a model the natural persistent control of HIV infection.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/inmunología , VIH-1/inmunología , Inflamación/inmunología , Leucocitos Mononucleares/inmunología , Replicación Viral , Adulto , Linfocitos T CD4-Positivos/virología , Citocinas/metabolismo , Femenino , Infecciones por VIH/virología , Humanos , Inflamación/virología , Leucocitos Mononucleares/virología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Carga Viral
15.
Clin Sci (Lond) ; 133(8): 997-1010, 2019 04 30.
Artículo en Inglés | MEDLINE | ID: mdl-30952809

RESUMEN

The immunological, biochemical and molecular mechanisms associated with poor immune recovery are far from known, and metabolomic profiling offers additional value to traditional soluble markers. Here, we present novel and relevant data that could contribute to better understanding of the molecular mechanisms preceding a discordant response and HIV progression under suppressive combined antiretroviral therapy (cART). Integrated data from nuclear magnetic resonance (NMR)-based lipoprotein profiles, mass spectrometry (MS)-based metabolomics and soluble plasma biomarkers help to build prognostic and immunological progression tools that enable the differentiation of HIV-infected subjects based on their immune recovery status after 96 weeks of suppressive cART. The metabolomic signature of ART-naïve HIV subjects with a subsequent late immune recovery is the expression of pro-inflammatory molecules and glutaminolysis, which is likely related to elevate T-cell turnover in these patients. The knowledge about how these metabolic pathways are interconnected and regulated provides new targets for future therapeutic interventions not only in HIV infection but also in other metabolic disorders such as human cancers where glutaminolysis is the alternative pathway for energy production in tumor cells to meet their requirement of rapid proliferation.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Glutamina/metabolismo , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Lipoproteínas/sangre , Adulto , Biomarcadores/sangre , Estudios de Cohortes , Estudios de Seguimiento , Infecciones por VIH/metabolismo , VIH-1 , Humanos , Espectroscopía de Resonancia Magnética , Masculino , Espectrometría de Masas , Metabolómica , Persona de Mediana Edad
16.
Clin Infect Dis ; 66(12): 1910-1917, 2018 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-29272392

RESUMEN

Background: Interferon alpha (IFN-α) can potently reduce human immunodeficiency virus type 1 (HIV-1) replication in tissue culture and animal models, but may also modulate residual viral reservoirs that persist despite suppressive antiretroviral combination therapy. However, mechanisms leading to viral reservoir reduction during IFN-α treatment are unclear. Methods: We analyzed HIV-1 gag DNA levels in CD4 T cells by digital droplet polymerase chain reaction and CD8 T-cell and natural killer (NK) cell phenotypes by flow cytometry in a cohort of antiretroviral therapy-treated HIV-1/hepatitis C virus-coinfected patients (n = 67) undergoing treatment for hepatitis C infection with pegylated IFN-α and ribavirin for an average of 11 months. Results: We observed that IFN-α treatment induced a significant decrease in CD4 T-cell counts (P < .0001), in CD4 T-cell-associated HIV-1 DNA copies (P = .002) and in HIV-1 DNA copies per microliter of blood (P < .0001) in our study patients. Notably, HIV-1 DNA levels were unrelated to HIV-1-specific CD8 T-cell responses. In contrast, proportions of total NK cells, CD56brightCD16- NK cells, and CD56brightCD16+ NK cells were significantly correlated with reduced levels of CD4 T-cell-associated HIV-1 DNA during IFN-α treatment, especially when coexpressing the activation markers NKG2D and NKp30. Conclusions: These data suggest that the reduction of viral reservoir cells during treatment with IFN-α is primarily attributable to antiviral activities of NK cells.


Asunto(s)
Coinfección/tratamiento farmacológico , ADN Viral/sangre , Infecciones por VIH/tratamiento farmacológico , Hepatitis C/tratamiento farmacológico , Interferón-alfa/uso terapéutico , Células Asesinas Naturales/inmunología , Polietilenglicoles/uso terapéutico , Adulto , Anciano , Terapia Antirretroviral Altamente Activa , Estudios de Cohortes , Coinfección/inmunología , Coinfección/virología , Reservorios de Enfermedades/virología , Femenino , Infecciones por VIH/virología , VIH-1/efectos de los fármacos , VIH-1/genética , Hepacivirus/efectos de los fármacos , Hepatitis C/virología , Humanos , Células Asesinas Naturales/efectos de los fármacos , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Ribavirina/uso terapéutico , España , Carga Viral , Productos del Gen gag del Virus de la Inmunodeficiencia Humana/genética
17.
Lab Invest ; 98(4): 500-511, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29348565

RESUMEN

The size of peripheral T-cell pool is kept constant throughout life. However, a decline in lymphocyte numbers is a feature of several human disorders, in which fast and slow homeostatic proliferation play a crucial role. Several in vitro and in vivo models have been developed to study such processes. Nevertheless, self- and commensal- antigens, well-known triggers of homeostatic proliferation, have not been examined in these models. We have designed an in vitro culture of human T-cells exposed to rIL7 and autologous antigen-presenting cells (aAPC) that allows the simultaneous characterization of the different types of homeostatic proliferation. Using our model, we first confirmed that both rIL7 and aAPC are survival signals ultimately leading to homeostatic proliferation. In addition, we explored the modulation of different anti-apoptotic, proliferative, activation and homing markers during fast and slow homeostatic proliferation. Finally, different subsets of Treg were generated during homeostatic proliferation in our model. In summary, our in vitro system is able to simultaneously reproduce both types of homeostatic proliferation of human naive CD4 T-cells, and allows the characterization of these processes. Our in vitro system is a useful tool to explore specific features of human homeostatic proliferation in different human lymphopenia-related disorders and could be used as a cell therapy approach.


Asunto(s)
Linfocitos T CD4-Positivos/fisiología , Técnicas de Cultivo de Célula , Células Presentadoras de Antígenos , Proliferación Celular , Supervivencia Celular , Homeostasis , Interleucina-17 , Proteínas Recombinantes
18.
Artículo en Inglés | MEDLINE | ID: mdl-29084751

RESUMEN

The response to the HBV vaccine in HIV-infected patients is deficient. Our aim was to analyze whether a suppressive combined antiretroviral treatment (cART) containing maraviroc (MVC-cART) was associated with a better response to HBV vaccine. Fifty-seven patients on suppressor cART were administered the HBV vaccine. The final response, the early response, and the maintenance of the response were assessed. An anti-HBs titer of >10 mIU/ml was considered a positive response. A subgroup of subjects was simultaneously vaccinated against hepatitis A virus (HAV). Lineal regression analyses were performed to determine demographic, clinical, and immunological factors associated with the anti-HBs titer. Vaccine response was achieved in 90% of the subjects. After 1 year, 81% maintained protective titers. Only simultaneous HAV vaccination was independently associated with the magnitude of the response in anti-HBs titers, with a P value of 0.045 and a regression coefficient (B) [95% confident interval (CI)] of 236 [5 to 468]. In subjects ≤50 years old (n = 42), MVC-cART was independently associated with the magnitude of the response (P = 0.009; B [95% CI], 297 [79 to 516]) together with previous vaccination and simultaneous HAV vaccination. High rates of HBV vaccine response can be achieved by revaccination, simultaneous HAV vaccination, and administration of cARTs including MVC. MVC may be considered for future vaccination protocols in patients on suppressive cART.


Asunto(s)
Antirretrovirales/uso terapéutico , Vacunas contra Hepatitis B/inmunología , Virus de la Hepatitis B/efectos de los fármacos , Virus de la Hepatitis B/inmunología , Hepatitis B/tratamiento farmacológico , Hepatitis B/inmunología , Maraviroc/uso terapéutico , Adulto , Femenino , Hepatitis B/virología , Anticuerpos contra la Hepatitis B/inmunología , Humanos , Inmunización Secundaria/métodos , Masculino , Persona de Mediana Edad , Vacunación/métodos
19.
BMC Med ; 16(1): 30, 2018 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-29490663

RESUMEN

BACKGROUND: Despite long-lasting HIV replication control, a significant proportion of elite controller (EC) patients may experience CD4 T-cell loss. Discovering perturbations in immunological parameters could help our understanding of the mechanisms that may be operating in those patients experiencing loss of immunological control. METHODS: A case-control study was performed to evaluate if alterations in different T-cell homeostatic parameters can predict CD4 T-cell loss in ECs by comparing data from EC patients showing significant CD4 decline (cases) and EC patients showing stable CD4 counts (controls). The partial least-squares-class modeling (PLS-CM) statistical methodology was employed to discriminate between the two groups of patients, and as a predictive model. RESULTS: Herein, we show that among T-cell homeostatic alterations, lower levels of naïve and recent thymic emigrant subsets of CD8 cells and higher levels of effector and senescent subsets of CD8 cells as well as higher levels of exhaustion of CD4 cells, measured prior to CD4 T-cell loss, predict the loss of immunological control. CONCLUSIONS: These data indicate that the parameters of T-cell homeostasis may identify those EC patients with a higher proclivity to CD4 T-cell loss. Our results may open new avenues for understanding the mechanisms underlying immunological progression despite HIV replication control, and eventually, for finding a functional cure through immune-based clinical trials.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Infecciones por VIH/inmunología , Homeostasis , Adulto , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad
20.
Proc Biol Sci ; 285(1877)2018 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-29669895

RESUMEN

Elucidating how ecological and evolutionary mechanisms interact to produce and maintain biodiversity is a fundamental problem in evolutionary ecology. Here, we focus on how physiological evolution affects performance and species coexistence along the thermal niche axis in replicated radiations of Anolis lizards best known for resource partitioning based on morphological divergence. We find repeated divergence in thermal physiology within these radiations, and that this divergence significantly affects performance within natural thermal environments. Morphologically similar species that co-occur invariably differ in their thermal physiology, providing evidence that physiological divergence facilitates species coexistence within anole communities. Despite repeated divergence, phylogenetic comparative analyses indicate that physiological traits have evolved more slowly than key morphological traits related to the structural niche. Phylogenetic analyses also reveal that physiological divergence is correlated with divergence in broad-scale habitat climatic features commonly used to estimate thermal niche evolution, but that the latter incompletely predicts variation in the former. We provide comprehensive evidence for repeated adaptive evolution of physiological divergence within Anolis adaptive radiations, including the complementary roles of physiological and morphological divergence in promoting community-level diversity. We recommend greater integration of performance-based traits into analyses of climatic niche evolution, as they facilitate a more complete understanding of the phenotypic and ecological consequences of climatic divergence.


Asunto(s)
Evolución Biológica , Ecosistema , Lagartos/fisiología , Animales , Jamaica , Filogenia , Puerto Rico , Temperatura , Islas Virgenes de los Estados Unidos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA