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1.
Nature ; 610(7933): 693-698, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-36224389

RESUMEN

Soils are the foundation of all terrestrial ecosystems1. However, unlike for plants and animals, a global assessment of hotspots for soil nature conservation is still lacking2. This hampers our ability to establish nature conservation priorities for the multiple dimensions that support the soil system: from soil biodiversity to ecosystem services. Here, to identify global hotspots for soil nature conservation, we performed a global field survey that includes observations of biodiversity (archaea, bacteria, fungi, protists and invertebrates) and functions (critical for six ecosystem services) in 615 composite samples of topsoil from a standardized survey in all continents. We found that each of the different ecological dimensions of soils-that is, species richness (alpha diversity, measured as amplicon sequence variants), community dissimilarity and ecosystem services-peaked in contrasting regions of the planet, and were associated with different environmental factors. Temperate ecosystems showed the highest species richness, whereas community dissimilarity peaked in the tropics, and colder high-latitudinal ecosystems were identified as hotspots of ecosystem services. These findings highlight the complexities that are involved in simultaneously protecting multiple ecological dimensions of soil. We further show that most of these hotspots are not adequately covered by protected areas (more than 70%), and are vulnerable in the context of several scenarios of global change. Our global estimation of priorities for soil nature conservation highlights the importance of accounting for the multidimensionality of soil biodiversity and ecosystem services to conserve soils for future generations.


Asunto(s)
Biodiversidad , Conservación de los Recursos Naturales , Mapeo Geográfico , Microbiología del Suelo , Suelo , Animales , Conservación de los Recursos Naturales/métodos , Suelo/parasitología , Invertebrados , Archaea
2.
Cell ; 147(5): 1011-23, 2011 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-22118459

RESUMEN

Atypical antipsychotic drugs, such as clozapine and risperidone, have a high affinity for the serotonin 5-HT(2A) G protein-coupled receptor (GPCR), the 2AR, which signals via a G(q) heterotrimeric G protein. The closely related non-antipsychotic drugs, such as ritanserin and methysergide, also block 2AR function, but they lack comparable neuropsychological effects. Why some but not all 2AR inhibitors exhibit antipsychotic properties remains unresolved. We now show that a heteromeric complex between the 2AR and the G(i)-linked GPCR, metabotropic glutamate 2 receptor (mGluR2), integrates ligand input, modulating signaling output and behavioral changes. Serotonergic and glutamatergic drugs bind the mGluR2/2AR heterocomplex, which then balances Gi- and Gq-dependent signaling. We find that the mGluR2/2AR-mediated changes in Gi and Gq activity predict the psychoactive behavioral effects of a variety of pharmocological compounds. These observations provide mechanistic insight into antipsychotic action that may advance therapeutic strategies for disorders including schizophrenia and dementia.


Asunto(s)
Antipsicóticos/farmacología , Receptores Adrenérgicos beta 2/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Transducción de Señal , Anfetaminas/farmacología , Animales , Clozapina/farmacología , Dimerización , Relación Dosis-Respuesta a Droga , Lóbulo Frontal/efectos de los fármacos , Lóbulo Frontal/metabolismo , Metisergida/farmacología , Ratones , Oocitos , Canales de Potasio de Rectificación Interna/metabolismo , Xenopus
3.
PLoS Genet ; 19(3): e1010490, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36972246

RESUMEN

Antimicrobial resistance (AMR) remains a major threat to global health. To date, tractable approaches that decipher how AMR emerges within a bacterial population remain limited. Here, we developed a framework that exploits genetic diversity from environmental bacterial populations to decode emergent phenotypes such as AMR. OmpU is a porin that can make up to 60% of the outer membrane of Vibrio cholerae, the cholera pathogen. This porin is directly associated with the emergence of toxigenic clades and confers resistance to numerous host antimicrobials. In this study, we examined naturally occurring allelic variants of OmpU in environmental V. cholerae and established associations that connected genotypic variation with phenotypic outcome. We covered the landscape of gene variability and found that the porin forms two major phylogenetic clusters with striking genetic diversity. We generated 14 isogenic mutant strains, each encoding a unique ompU allele, and found that divergent genotypes lead to convergent antimicrobial resistance profiles. We identified and characterized functional domains in OmpU unique to variants conferring AMR-associated phenotypes. Specifically, we identified four conserved domains that are linked with resistance to bile and host-derived antimicrobial peptides. Mutant strains for these domains exhibit differential susceptibility patterns to these and other antimicrobials. Interestingly, a mutant strain in which we exchanged the four domains of the clinical allele for those of a sensitive strain exhibits a resistance profile closer to a porin deletion mutant. Finally, using phenotypic microarrays, we uncovered novel functions of OmpU and their connection with allelic variability. Our findings highlight the suitability of our approach towards dissecting the specific protein domains associated with the emergence of AMR and can be naturally extended to other bacterial pathogens and biological processes.


Asunto(s)
Antiinfecciosos , Vibrio cholerae , Adhesinas Bacterianas/genética , Proteínas de la Membrana Bacteriana Externa/metabolismo , Antibacterianos/farmacología , Alelos , Filogenia , Dominios Proteicos , Farmacorresistencia Bacteriana/genética , Vibrio cholerae/genética , Vibrio cholerae/metabolismo , Porinas/genética , Porinas/metabolismo
4.
Nature ; 568(7753): 517-520, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30971829

RESUMEN

The detection of methane on Mars has been interpreted as indicating that geochemical or biotic activities could persist on Mars today1. A number of different measurements of methane show evidence of transient, locally elevated methane concentrations and seasonal variations in background methane concentrations2-5. These measurements, however, are difficult to reconcile with our current understanding of the chemistry and physics of the Martian atmosphere6,7, which-given methane's lifetime of several centuries-predicts an even, well mixed distribution of methane1,6,8. Here we report highly sensitive measurements of the atmosphere of Mars in an attempt to detect methane, using the ACS and NOMAD instruments onboard the ESA-Roscosmos ExoMars Trace Gas Orbiter from April to August 2018. We did not detect any methane over a range of latitudes in both hemispheres, obtaining an upper limit for methane of about 0.05 parts per billion by volume, which is 10 to 100 times lower than previously reported positive detections2,4. We suggest that reconciliation between the present findings and the background methane concentrations found in the Gale crater4 would require an unknown process that can rapidly remove or sequester methane from the lower atmosphere before it spreads globally.

6.
Mol Genet Genomics ; 299(1): 60, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38801463

RESUMEN

Type 2 diabetes (DM2) is an increasingly prevalent disease that challenges tuberculosis (TB) control strategies worldwide. It is significant that DM2 patients with poor glycemic control (PDM2) are prone to developing tuberculosis. Furthermore, elucidating the molecular mechanisms that govern this susceptibility is imperative to address this problem. Therefore, a pilot transcriptomic study was performed. Human blood samples from healthy controls (CTRL, HbA1c < 6.5%), tuberculosis (TB), comorbidity TB-DM2, DM2 (HbA1c 6.5-8.9%), and PDM2 (HbA1c > 10%) groups (n = 4 each) were analyzed by differential expression using microarrays. We use a network strategy to identify potential molecular patterns linking the differentially expressed genes (DEGs) specific for TB-DM2 and PDM2 (p-value < 0.05, fold change > 2). We define OSM, PRKCD, and SOCS3 as key regulatory genes (KRGs) that modulate the immune system and related pathways. RT-qPCR assays confirmed upregulation of OSM, PRKCD, and SOCS3 genes (p < 0.05) in TB-DM2 patients (n = 18) compared to CTRL, DM2, PDM2, or TB groups (n = 17, 19, 15, and 9, respectively). Furthermore, OSM, PRKCD, and SOCS3 were associated with PDM2 susceptibility pathways toward TB-DM2 and formed a putative protein-protein interaction confirmed in STRING. Our results reveal potential molecular patterns where OSM, PRKCD, and SOCS3 are KRGs underlying the compromised immune response and susceptibility of patients with PDM2 to develop tuberculosis. Therefore, this work paved the way for fundamental research of new molecular targets in TB-DM2. Addressing their cellular implications, and the impact on the diagnosis, treatment, and clinical management of TB-DM2 could help improve the strategy to end tuberculosis for this vulnerable population.


Asunto(s)
Diabetes Mellitus Tipo 2 , Proteína 3 Supresora de la Señalización de Citocinas , Tuberculosis , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Proyectos Piloto , Tuberculosis/genética , Tuberculosis/sangre , Masculino , Femenino , Persona de Mediana Edad , Proteína 3 Supresora de la Señalización de Citocinas/genética , Proteína 3 Supresora de la Señalización de Citocinas/metabolismo , Control Glucémico , Perfilación de la Expresión Génica , Anciano , Adulto , Redes Reguladoras de Genes , Estudios de Casos y Controles , Transcriptoma/genética , Susceptibilidad a Enfermedades
7.
Int J Obes (Lond) ; 48(5): 612-625, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38273033

RESUMEN

BACKGROUND: Childhood obesity and overweight are associated with musculoskeletal pain, but the association between low back pain (LBP) and overweight/obesity in this population needs clarification. The objective of this meta-analysis is to ascertain the relationship between LBP and obesity/overweight in children and adolescents. METHODS: Various databases and specialized journals were queried from inception to October 2022. Encompassed were all studies examining the association between overweight or obesity and LBP among participants aged 6 to 18 years. The ROBINS-E tool was employed to assess bias. Random-effects models were used to pool results across studies, with location-scale models used to search for moderator variables where evidence of heterogeneity was found. RESULTS: In total, 34 studies were incorporated. Four studies had a low risk of bias, while the remaining studies had some concerns. Nine studies evinced an association between overweight and LBP, in contrast to normal weight, yielding an OR of 1.13 (95% CI 1.10-1.16) and no heterogeneity. Eight studies demonstrated a similar association between obesity and LBP compared to normal weight, with an OR of 1.27 (95% CI 1.20-1.34) and no heterogeneity. Ten studies established an association between overweight/obesity and LBP compared to normal weight, yielding an OR of 1.18 (95% CI 1.14-1.23) and no heterogeneity. Finally, nineteen studies showcased an association between body mass index (BMI) and LBP, with an OR of 1.19 (95% CI 1.03-1.39) with evidence of heterogeneity. For this last analysis, we compared the mean BMI in groups and transformed results to log OR, and then retransformed to OR. CONCLUSION: Overweight and obesity may be risk factors for LBP in children and adolescents. The association between LBP and obesity appears to be stronger than with overweight. However, the analysis revealed considerable heterogeneity and risk of bias across studies.


Asunto(s)
Dolor de la Región Lumbar , Sobrepeso , Obesidad Infantil , Humanos , Adolescente , Dolor de la Región Lumbar/epidemiología , Dolor de la Región Lumbar/etiología , Niño , Obesidad Infantil/epidemiología , Obesidad Infantil/complicaciones , Factores de Riesgo , Sobrepeso/complicaciones , Sobrepeso/epidemiología , Femenino , Masculino
8.
J Virol ; 97(2): e0165522, 2023 02 28.
Artículo en Inglés | MEDLINE | ID: mdl-36719240

RESUMEN

The implementation and access to combined antiretroviral treatment (cART) have dramatically improved the quality of life of people living with HIV (PLWH). However, some comorbidities, such as neurological disorders associated with HIV infection still represent a serious clinical challenge. Soluble factors in plasma that are associated with control of HIV replication and neurological dysfunction could serve as early biomarkers and as new therapeutic targets for this comorbidity. We used a customized antibody array for determination of blood plasma factors in 40 untreated PLWH with different levels of viremia and found sirtuin-2 (SIRT2), an NAD-dependent deacetylase, to be strongly associated with elevated viral loads and HIV provirus levels, as well as with markers of neurological damage (a-synuclein [SNCA], brain-derived neurotrophic factor [BDNF], microtubule-associated protein tau [MAPT], and neurofilament light protein [NFL]). Also, longitudinal analysis in HIV-infected individuals with immediate (n = 9) or delayed initiation (n = 10) of cART revealed that after 1 year on cART, SIRT2 plasma levels differed between both groups and correlated inversely with brain orbitofrontal cortex involution. Furthermore, targeting SIRT2 with specific small-molecule inhibitors in in vitro systems using J-LAT A2 and primary glial cells led to diminished HIV replication and virus reactivation from latency. Our data thus identify SIRT2 as a novel biomarker of uncontrolled HIV infection, with potential impact on neurological dysfunction and offers a new therapeutic target for HIV treatment and cure. IMPORTANCE Neurocognitive disorders are frequently reported in people living with HIV (PLWH) even with the introduction of combined antiretroviral treatment (cART). To identify biomarkers and potential therapeutic tools to target HIV infection in peripheral blood and in the central nervous system (CNS), plasma proteomics were applied in untreated chronic HIV-infected individuals with different levels of virus control. High plasma levels of sirtuin-2 (SIRT2), an NAD+ deacetylase, were detected in uncontrolled HIV infection and were strongly associated with plasma viral load and proviral levels. In parallel, SIRT2 levels in the peripheral blood and CNS were associated with markers of neurological damage and brain involution and were more pronounced in individuals who initiated cART later in infection. In vitro infection experiments using specific SIRT2 inhibitors suggest that specific targeting of SIRT2 could offer new therapeutic treatment options for HIV infections and their associated neurological dysfunction.


Asunto(s)
Infecciones por VIH , Enfermedades del Sistema Nervioso , Sirtuina 2 , Humanos , Biomarcadores , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Proteínas de Neurofilamentos/metabolismo , Provirus/metabolismo , Calidad de Vida , Sirtuina 2/metabolismo , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/etiología , Enfermedades del Sistema Nervioso/virología , Carga Viral
9.
Glob Chang Biol ; 30(5): e17295, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38804108

RESUMEN

Plant-soil biodiversity interactions are fundamental for the functioning of terrestrial ecosystems. Yet, the existence of a set of globally distributed topsoil microbial and small invertebrate organisms consistently associated with land plants (i.e., their consistent soil-borne microbiome), together with the environmental preferences and functional capabilities of these organisms, remains unknown. We conducted a standardized field survey under 150 species of land plants, including 58 species of bryophytes and 92 of vascular plants, across 124 locations from all continents. We found that, despite the immense biodiversity of soil organisms, the land plants evaluated only shared a small fraction (less than 1%) of all microbial and invertebrate taxa that were present across contrasting climatic and soil conditions and vegetation types. These consistent taxa were dominated by generalist decomposers and phagotrophs and their presence was positively correlated with the abundance of functional genes linked to mineralization. Finally, we showed that crossing environmental thresholds in aridity (aridity index of 0.65, i.e., the transition from mesic to dry ecosystems), soil pH (5.5; i.e., the transition from acidic to strongly acidic soils), and carbon (less than 2%, the lower limit of fertile soils) can result in drastic disruptions in the associations between land plants and soil organisms, with potential implications for the delivery of soil ecosystem processes under ongoing global environmental change.


Asunto(s)
Embryophyta , Microbiota , Microbiología del Suelo , Biodiversidad , Suelo/química
10.
Nanotechnology ; 35(28)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38522104

RESUMEN

Surface enhanced Raman spectroscopy (SERS) is a powerful analytical technique that has found application in the trace detection of a wide range of contaminants. In this paper, we report on the fabrication of 2D silver nanodendrites, on silicon chips, synthesized by electrochemical reduction of AgNO3at microelectrodes. The formation of nanodendrites is tentatively explained in terms of electromigration and diffusion of silver ions. Electrochemical characterization suggests that the nanodendrites do not stay electrically connected to the microelectrode. The substrates show SERS activity with an enhancement factor on the order of 106. Density functional theory simulations were carried out to investigate the suitability of the fabricated substrate for pesticide monitoring. These substrates can be functionalized with cyclodextrin macro molecules to help with the detection of molecules with low affinity with silver surfaces. A proof of concept is demonstrated with the detection of the herbicide 2-methyl-4-chlorophenoxyacetic acid (MCPA).

11.
Phys Chem Chem Phys ; 26(13): 10183-10190, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38497123

RESUMEN

Sequestration of small molecule guests in the cavity of a water-soluble deep cavitand host has a variety of effects on their NMR properties. The effects of encapsulation on the longitudinal (T1) and transverse (T2) relaxation times of the protons in variably sized guest molecules are analyzed here, using inversion recovery and spin-echo experiments. Sequestration of neutral organic species from the bulk solvent reduces the overall proton relaxation times, but the magnitude of this effect on different protons in the same molecule has a variety of contributors, from the motion of the guest when bound, to the position of the protons in the cavity and the magnetic anisotropy induced by the aromatic walls of the host. These subtle effects can have large consequences on the environment experienced by the bound guest, and this sheds light on the nature of small molecules in enclosed environments.

12.
Tob Control ; 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38378212

RESUMEN

Young health advocates have the legitimate aspiration to be masters of their future and are increasingly contributing to public health research and practice worldwide, yet their potential to contribute to the documentation and communication of outputs from public health conferences has not been fully realised. This short communication highlights the Youth Committee of the 2023 European Conference on Tobacco or Health as an example of youth involvement in a major public health conference focused on tobacco control. The authors explore the benefits, practicalities and challenges of incorporating young professionals into conference workflow, including creativity, networking and engagement with broader public health challenges within their communities. This article emphasises the active participation of Youth Committees in public health fora as a model for future conferences and underscores a commitment to achieving a tobacco-free generation.

13.
Ophthalmologica ; 2024 Mar 17.
Artículo en Inglés | MEDLINE | ID: mdl-38493775

RESUMEN

INTRODUCTION: The choroid and its role in posterior segment pathology has become an increasing subject of study. The objective of the present study was to analyze choroidal thickness (CT) in healthy eyes by widefield (WF) optical coherence tomography (OCT) up to the periphery and to compare the reliability of manual versus automatic measurement. METHODS: Cross-sectional and non-interventional study conducted on 191 healthy eyes of 101 patients. All patients were scanned by using WF-OCT (Xephilio WF-OCT S1; Canon Corp, Tokyo, Japan). CT was measured in 2000 µm intervals automatically using the built-in software and manually by two masked observers. All analyses were performed using the IBM-PSSS statistical software program (IBM-SPSS, v. 28.0.0.0, Chicago, IL, USA). RESULTS: CT was measured in 100% of the sample. The mean age of the study cohort was 39.05±19.06 years old. Mean subfoveal (SF)CT measured automatically was 343.67±84.18 µm and manually was 336.55±75.57 µm. The thickest point was located 2000 µm from the fovea in the superior sector in 62.83% of the subjects. According to age distribution, mean CT became significantly thinner from 40 years of age. When comparing automatic and manually measuring, the intraclass correlation coefficient was excellent (p<0.01) in all quadrants. Moreover, manual measurement interobserver agreement was excellent in all quadrants (p<0.01). CONCLUSION: The automatic system is valid and serves as the basis of choroid measurement. In more than 50% of the healthy subjects, superior CT is thicker than subfoveolar CT and mean CT became significantly thinner from 40 years of age.

14.
Sensors (Basel) ; 24(5)2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38475039

RESUMEN

Children with autism spectrum disorder (ASD) have deficits that affect their social relationships, communication, and flexibility in reasoning. There are different types of treatment (pharmacological, educational, psychological, and rehabilitative). Currently, one way to address this problem is by using robotic systems to address the abilities that are altered in these children. The aim of this review will be to analyse the effectiveness of the incorporation of the different robotic systems currently existing in the treatment of children up to 10 years of age diagnosed with autism. A systematic review has been carried out in the PubMed, Scopus, Web of Science, and Dialnet databases, with the following descriptors: child, autism, and robot. The search yielded 578 papers, and nine were selected after the application of the PRISMA guideline. The quality of the studies was analysed with the PEDRo scale, and only those with a score between four and six were selected. From this study, the conclusion is that the use of robots, in general, improves children's behaviour in the short term, but longer-term experiences are necessary to achieve more conclusive results.


Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Robótica , Niño , Humanos , Preescolar , Trastorno del Espectro Autista/psicología , Relaciones Interpersonales , Comunicación
15.
Sensors (Basel) ; 24(6)2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38544137

RESUMEN

This paper presents an innovative dataset designed explicitly for challenging agricultural environments, such as greenhouses, where precise location is crucial, but GNNS accuracy may be compromised by construction elements and the crop. The dataset was collected using a mobile platform equipped with a set of sensors typically used in mobile robots as it was moved through all the corridors of a typical Mediterranean greenhouse featuring tomato crops. This dataset presents a unique opportunity for constructing detailed 3D models of plants in such indoor-like spaces, with potential applications such as robotized spraying. For the first time, to the authors' knowledge, a dataset suitable to test simultaneous localization and mapping (SLAM) methods is presented in a greenhouse environment, which poses unique challenges. The suitability of the dataset for this purpose is assessed by presenting SLAM results with state-of-the-art algorithms. The dataset is available online.

16.
Gastroenterol Hepatol ; : 502222, 2024 Jun 20.
Artículo en Inglés, Español | MEDLINE | ID: mdl-38908682

RESUMEN

BACKGROUND AND AIMS: Chronic hepatitis D (CHD) is a severe form of chronic viral hepatitis. The estimated HDV prevalence in Spain is around 5% of patients with hepatitis B. Reimbursement of new antiviral therapies (Bulevirtide, BLV) was delayed in our country until February 2024. We aimed to characterize the clinical profile of patients with HDV/HBV infection in Spain and current barriers in their management at the time of BLV approval. METHOD: Multicenter registry including patients with positive anti-HDV serology actively monitored in 30 Spanish centers. Epidemiological, clinical and virological variables were recorded at the start of follow-up and at the last visit. RESULTS: We identified 329 anti-HDV patients, 41% were female with median age 51 years. The most common geographical origin was Spain (53%) and East Europe (24%). Patients from Spain were older and had HCV and HIV coinfection probably associated to past drug injection (p<0.01). HDV-RNA was positive in 138 of 221 assessed (62%). Liver cirrhosis was present at diagnosis in 33% and it was more frequent among viremic patients (58% vs 25%, p<0.01). After a median follow-up of 6 (3-12) years, 44 (16%) resolved infection (18 spontaneously and 26 after Peg-INF). An additional 10% of patients developed cirrhosis (n=137) during follow-up (45% had portal hypertension and 14% liver decompensation). Liver disease progression was associated to persisting viremia. CONCLUSION: One-third of the patients with CHD already have cirrhosis at diagnosis. Persistence of positive viremia is associated to rapid liver disease progression. Importantly, barriers to locally determine/quantify HDV-RNA were present.

17.
J Biol Chem ; 298(11): 102481, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36100039

RESUMEN

Prenatal environmental insults increase the risk of neurodevelopmental psychiatric conditions in the offspring. Structural modifications of dendritic spines are central to brain development and plasticity. Using maternal immune activation (MIA) as a rodent model of prenatal environmental insult, previous results have reported dendritic structural deficits in the frontal cortex. However, very little is known about the molecular mechanism underlying MIA-induced synaptic structural alterations in the offspring. Using prenatal (E12.5) injection with polyinosinic-polycytidylic acid potassium salt as a mouse MIA model, we show here that upregulation of the serotonin 5-HT2A receptor (5-HT2AR) is at least in part responsible for some of the effects of prenatal insults on frontal cortex dendritic spine structure and sensorimotor gating processes. Mechanistically, we report that this upregulation of frontal cortex 5-HT2AR expression is associated with MIA-induced reduction of nuclear translocation of the glucocorticoid receptor (GR) and, consequently, a decrease in the enrichment of GR at the 5-HT2AR promoter. The translational significance of these preclinical findings is supported by data in postmortem human brain samples suggesting dysregulation of GR translocation in frontal cortex of schizophrenia subjects. We also found that repeated corticosterone administration augmented frontal cortex 5-HT2AR expression and reduced GR binding to the 5-HT2AR promoter. However, virally (adeno-associated virus) mediated augmentation of GR function reduced frontal cortex 5-HT2AR expression and improved sensorimotor gating processes via 5-HT2AR. Together, these data support a negative regulatory relationship between GR signaling and 5-HT2AR expression in the mouse frontal cortex that may carry implications for the pathophysiology underlying 5-HT2AR dysregulation in neurodevelopmental psychiatric disorders.


Asunto(s)
Trastornos del Neurodesarrollo , Esquizofrenia , Embarazo , Femenino , Ratones , Humanos , Animales , Serotonina , Receptores de Glucocorticoides , Modelos Animales de Enfermedad , Trastornos del Neurodesarrollo/genética , Esquizofrenia/genética , Esquizofrenia/metabolismo , Receptor de Serotonina 5-HT2A/genética
18.
Environ Microbiol ; 25(6): 1136-1154, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36755376

RESUMEN

Evolutionary adaptations of prokaryotes to the environment sometimes result in genome reduction. Our knowledge of this phenomenon among free-living bacteria remains scarce. We address the dynamics and limits of genome reduction by examining one of the most abundant bacteria in the ocean, the SAR86 clade. Despite its abundance, comparative genomics has been limited by the absence of pure cultures and the poor representation in metagenome-assembled genomes. We co-assembled multiple previously available single-amplified genomes to obtain the first complete genomes from members of the four families. All families showed a convergent evolutionary trajectory with characteristic features of streamlined genomes, most pronounced in the TMED112 family. This family has a genome size of ca. 1 Mb and only 1 bp as median intergenic distance, exceeding values found in other abundant microbes such as SAR11, OM43 and Prochlorococcus. This genomic simplification led to a reduction in the biosynthesis of essential molecules, DNA repair-related genes, and the ability to sense and respond to environmental factors, which could suggest an evolutionary dependence on other co-occurring microbes for survival (Black Queen hypothesis). Therefore, these reconstructed genomes within the SAR86 clade provide new insights into the limits of genome reduction in free-living marine bacteria.


Asunto(s)
Bacterias , Genoma Bacteriano , Humanos , Genoma Bacteriano/genética , Bacterias/genética , Genómica , Evolución Biológica , Metagenoma , Filogenia
19.
Ann Rheum Dis ; 82(12): 1594-1605, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37666646

RESUMEN

BACKGROUND: The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic UBA1 variants. OBJECTIVES: To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines. METHODS: Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex. RESULTS: Genetic analyses of enrolled patients (n=42) identified 30 patients carrying UBA1 pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the UBA1 variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease. CONCLUSION: Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the UBA1 mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms.


Asunto(s)
Artritis , Mosaicismo , Adulto , Humanos , Masculino , Femenino , Citocinas/genética , Ferritinas , Glucocorticoides , Mutación
20.
Artículo en Inglés | MEDLINE | ID: mdl-37605998

RESUMEN

Strain HF14-78462T is an environmental bacterium found in clinical samples from an immunocompromized patient in 2014 at Hospital Universitari i Politècnic La Fe (Valencia, Spain). Phenotypically, strain HF14-78462T cells were Gram-stain-negative, aerobic, non-spore forming and non-motile small rods which formed mucous and whitish-translucent colonies when incubated at 20-36 °C. Phylogenetic analyses based on the 16S rRNA genes and the whole genomes of closest sequenced relatives confirmed that strain HF14-78462T is affiliated with the genus Starkeya. The strain was oxidase, catalase and urease positive; but indole, lysine decarboxylase, ornithine decarboxylase and DNase negative, did not produce H2S and was able to utilize a wide variety of carbon sources including acetamide, adonitol, amygdalin, l-arabinose, citric acid, glucose, mannitol and melibiose. Unlike Starkeya novella and Starkeya koreensis, strain HF14-78462T failed to grow in thiosulphate-oxidizing media and had a narrower temperature growth range. Its genome was characterized by a size of 4.83 Mbp and a C+G content of 67.75 mol%. Major fatty acids were C18:1 ω7c, cyclo C19 : 0 and C16 : 0, its polar acids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and an aminophospholipid; while the ubiquinones were Q9 (1.8 %) and Q10 (98.2 %). Digital DNA-DNA hybridization values were 41 and 41.4 against S. novella and S. koreensis, respectively, while average nucleotide identity values were around 84 %. Phenotypic, average nucleotide identity and phylogenomic comparative studies suggest that strain HF14-78462T is a new representative of the genus Starkeya and the name Starkeya nomas sp. nov. is proposed. The type strain is HF14-78462T (=CECT 30124T=LMG 31874T).


Asunto(s)
Ácidos Grasos , Noma , Humanos , Ácidos Grasos/química , Filogenia , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana , Composición de Base , Bacterias
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