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1.
Nature ; 610(7933): 693-698, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36224389

RESUMO

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.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais , Mapeamento Geográfico , Microbiologia do Solo , Solo , Animais , Conservação dos Recursos Naturais/métodos , Solo/parasitologia , Invertebrados , Archaea
2.
Proc Natl Acad Sci U S A ; 121(43): e2407561121, 2024 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-39405353

RESUMO

UBR5 E3 ligase has been associated with cancer susceptibility and neuronal integrity, with functions in chromatin regulation and proteostasis. However, the functions of ubr5 within animals remain unclear due to lethality in both mammals and flies when disrupted. Using Caenorhabditis elegans, we show that UBR-5 E3 ligase is required for timely exit of stem fate and complete transition into multiple cell type descendants in an ectodermal blast lineage. Animals lacking intact UBR-5 function simultaneously exhibit both stem fate and differentiated fate in the same descendant cells. A functional screen of UBR-5 physical interactors allowed us to identify the UBE2D2/3 E2 conjugase LET-70 working with UBR-5 to exit stem fate. Strikingly, we revealed that another UBR-5 physical interactor, namely the nuclear poly(A)-binding protein PABPN1 ortholog PABP-2, worked antagonistically to UBR-5 and LET-70. Lowering pabp-2 levels restored normal transition of cell state out of stemness and promoted normal cell fusion when either ubr-5 or let-70 UBE2D function was compromised. The UBR-5-LET-70 and PABP-2 switch works independently of the stem pool size determined by pluripotency factors like lin-28. UBR-5 limits PABP-2 protein and reverses the PABP-2-dependent gene expression program including developmental, proteostasis, and innate immunity genes. Loss of ubr-5 rescues the developmental stall when pabp-2 is compromised. Disruption of ubr-5 elevates PABP-2 levels and prolongs expression of ectodermal and muscle stem markers at the transition to adulthood. Additionally, ubr-5 mutants exhibit an extended period of motility during aging and suppress pabp-2-dependent early onset of immobility.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Enzimas de Conjugação de Ubiquitina , Ubiquitina-Proteína Ligases , Animais , Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Diferenciação Celular , Células-Tronco/metabolismo , Células-Tronco/citologia , Enzimas de Conjugação de Ubiquitina/metabolismo , Enzimas de Conjugação de Ubiquitina/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética
3.
Cell ; 147(5): 1011-23, 2011 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-22118459

RESUMO

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.


Assuntos
Antipsicóticos/farmacologia , Receptores Adrenérgicos beta 2/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Transdução de Sinais , Anfetaminas/farmacologia , Animais , Clozapina/farmacologia , Dimerização , Relação Dose-Resposta a Droga , Lobo Frontal/efeitos dos fármacos , Lobo Frontal/metabolismo , Metisergida/farmacologia , Camundongos , Oócitos , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Xenopus
4.
PLoS Genet ; 19(3): e1010490, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36972246

RESUMO

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.


Assuntos
Anti-Infecciosos , Vibrio cholerae , Adesinas Bacterianas/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Antibacterianos/farmacologia , Alelos , Filogenia , Domínios Proteicos , Farmacorresistência Bacteriana/genética , Vibrio cholerae/genética , Vibrio cholerae/metabolismo , Porinas/genética , Porinas/metabolismo
6.
Nature ; 568(7753): 517-520, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30971829

RESUMO

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.

7.
Environ Microbiol ; 26(8): e16684, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39080854

RESUMO

The knowledge of the different population-level processes operating within a species, and the genetic variability of the individual prokaryotic genomes, is key to understanding the adaptability of microbial populations. Here, we characterized the flexible genome of ammonia-oxidizing archaeal (AOA) populations using a metagenomic recruitment approach and long-read (PacBio HiFi) metagenomic sequencing. In the lower photic zone of the western Mediterranean Sea (75 m deep), the genomes Nitrosopelagicus brevis CN25 and Nitrosopumilus catalinensis SPOT1 had the highest recruitment values among available complete AOA genomes. They were used to analyse the diversity of flexible genes (variable from strain to strain) by examining the long-reads located within the flexible genomic islands (fGIs) identified by their under-recruitment. Both AOA genomes had a large fGI involved in the glycosylation of exposed structures, highly variable, and rich in glycosyltransferases. N. brevis had two fGIs related to the transport of phosphorus and ammonium respectively. N. catalinensis had fGIs involved in phosphorus transportation and metal uptake. A fGI5 previously reported as 'unassigned function' in N. brevis could be associated with defense. These findings demonstrate that the microdiversity of marine microbe populations, including AOA, can be effectively characterized using an approach that incorporates third-generation sequencing metagenomics.


Assuntos
Amônia , Archaea , Genoma Arqueal , Metagenoma , Oxirredução , Água do Mar , Mar Mediterrâneo , Archaea/genética , Archaea/metabolismo , Archaea/classificação , Amônia/metabolismo , Água do Mar/microbiologia , Metagenômica , Filogenia , Variação Genética , Ilhas Genômicas , Biodiversidade
8.
Cell Physiol Biochem ; 58(4): 393-403, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39166656

RESUMO

BACKGROUND/AIMS: Due to rapid metabolic and growth rates during the first two years of life, the nutritional needs of young children are high. Given the small portion sizes consumed by children between the ages of 6 and 24 months, it is necessary to improve diets to meet the nutritional needs of this age group. Therefore, the analysis of lysine content is an important parameter in the evaluation of enriched foods. METHODS: The utilization of an enzymatic sensor employing lysine-α-oxidase (LOx) as a biorecognition element represents an alternative to the existing methods. This sensor was optimized for quantifying the lysine content in flour mixtures: Quinoa-Lablab purpureus rye - Lablab purpureus, and pole beans - Lablab purpureus, with a maximum ratio of 85g/100g. RESULTS: The addition of lablab purpureus significantly increased the lysine concentration in the enriched samples. When 30 percent was substituted in quinoa, it reached a 143 percent increase. And when 15 percent was substituted in the rye flour, the final concentration of this amino acid increased by 64 percent. In order to quantify the lysine concentration, it was necessary to optimize various parameters during the use of the sensor, e.g. a potentiometric signal was detected upon the depletion of oxygen present during the oxidation of lysine in the samples, and the sensor response was recorded at 2 s. This was possible due to the modification of the pH and the thickness of the membrane. The oxidation of lysine is catalyzed by LOx using molecular oxygen as the electron acceptor. The corresponding acidic compounds and hydrogen peroxide were formed in the reaction medium. CONCLUSION: It was possible to increase and verify the concentration of lysine in all the flours tested through the use of the biosensor, which turned out to be a valid method for controlling the nutritional quality of flours.


Assuntos
Técnicas Biossensoriais , Farinha , Lisina , Farinha/análise , Técnicas Biossensoriais/métodos , Lisina/análise , Lisina/metabolismo , Lisina/química , Alimentos Fortificados/análise , Secale/química , Secale/metabolismo , Chenopodium quinoa/química , Chenopodium quinoa/metabolismo , Aminoácido Oxirredutases/metabolismo
9.
Biochem Biophys Res Commun ; 735: 150854, 2024 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-39442452

RESUMO

BACKGROUND: Congenital hypothyroidism screening traditionally relies on detecting elevated thyroid-stimulating hormone levels, yet this approach may not detect a specific type of congenital hypothyroidism caused by iodotyrosine dehalogenase-1 (Dehal1) deficiency. The deficiency of this enzyme prevents the deiodination of mono-iodotyrosine (MIT) and di-iodotyrosine (DIT) in the process of iodine recycling. This underscores the potential use of iodotyrosine or its metabolites as non-invasive urinary biomarkers for early diagnosis of congenital hypothyroidism. However, the urinary metabolites of MIT/DIT have not yet been discovered. Thus, this study aimed to identify the urinary metabolites of iodotyrosine in experimental models. METHOD: Gas chromatography mass spectrometry was used to identify the urinary metabolites of iodotyrosine following intraperitoneal injection of MIT in rats. An isotope dilution mass spectrometric assay was developed for assessment of identified metabolites. Urine samples from Dehal1 knockout mice were used to confirm the results. RESULTS: We identified novel iodotyrosine metabolites, 3-iodo-4-hydroxyphenylacetic acid (IHPA), and 3,5-diiodo-4-hydroxyphenylacetic acid (Di-IHPA) as the primary urinary metabolites of MIT and DIT respectively. The concentrations of urinary IHPA and Di-IHPA were significantly higher in Dehal1 knockout mice. CONCLUSION: Our findings suggest that IHPA is detected in larger quantities and may hold more clinical significance than previously identified biomarkers like MIT and DIT, making it a promising candidate for diagnosing congenital hypothyroidism or other conditions associated with iodine recycling inhibition.


Assuntos
Cromatografia Gasosa-Espectrometria de Massas , Camundongos Knockout , Monoiodotirosina , Animais , Monoiodotirosina/urina , Monoiodotirosina/metabolismo , Ratos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Camundongos , Biomarcadores/urina , Masculino , Di-Iodotirosina/urina , Di-Iodotirosina/metabolismo , Hipotireoidismo Congênito/urina , Hipotireoidismo Congênito/metabolismo , Hipotireoidismo Congênito/diagnóstico , Ratos Sprague-Dawley , Hidrolases/metabolismo , Hidrolases/urina
10.
Mol Genet Genomics ; 299(1): 60, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801463

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2 , Proteína 3 Supressora da Sinalização de Citocinas , Tuberculose , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Projetos Piloto , Tuberculose/genética , Tuberculose/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Controle Glicêmico , Perfilação da Expressão Gênica , Idoso , Adulto , Redes Reguladoras de Genes , Estudos de Casos e Controles , Transcriptoma/genética , Suscetibilidade a Doenças
11.
Int J Obes (Lond) ; 48(5): 612-625, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38273033

RESUMO

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.


Assuntos
Dor Lombar , Sobrepeso , Obesidade Infantil , Humanos , Adolescente , Dor Lombar/epidemiologia , Dor Lombar/etiologia , Criança , Obesidade Infantil/epidemiologia , Obesidade Infantil/complicações , Fatores de Risco , Sobrepeso/complicações , Sobrepeso/epidemiologia , Feminino , Masculino
12.
J Virol ; 97(2): e0165522, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36719240

RESUMO

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.


Assuntos
Infecções por HIV , Doenças do Sistema Nervoso , Sirtuína 2 , Humanos , Biomarcadores , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , HIV-1 , Proteínas de Neurofilamentos/metabolismo , Provírus/metabolismo , Qualidade de Vida , Sirtuína 2/metabolismo , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/etiologia , Doenças do Sistema Nervoso/virologia , Carga Viral
13.
J Transl Med ; 22(1): 1003, 2024 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-39506809

RESUMO

BACKGROUND: Vasculogenic therapies explored for the treatment of peripheral artery disease (PAD) have encountered minimal success in clinical trials. Addressing this, B55α, an isoform of protein phosphatase 2A (PP2A), emerges as pivotal in vessel remodeling through activation of hypoxia-inducible factor 1α (HIF-1α). This study delves into the pharmacological profile of VCE-004.8 (Etrinabdione) and evaluates its efficacy in a preclinical model of critical limb ischemia, with a focus on its potential as a PP2A/B55α activator to induce angiogenesis and arteriogenesis. METHODS: Vascular endothelial cells were used for in vitro experiments. Aorta ring assay was performed to explore sprouting activity. Matrigel plug-in assay was used to assess the angiogenic potential. Critical limb ischemia (CLI) in mice was induced by double ligation in the femoral arteria. Endothelial vascular and fibrotic biomarkers were studied by immunohistochemistry and qPCR. Arteriogenesis was investigated by microvascular casting and micro-CT. Proteomic analysis in vascular tissues was analyzed by LC-MS/MS. Ex-vivo expression of B55α and biomarkers were investigated in artery samples from PAD patients. RESULTS: VCE-004.8 exhibited the ability to induce B55α expression and activate the intersecting pathways B55α/AMPK/Sirtuin 1/eNOS and B55α/PHD2/HIF-1α. VCE-004.8 prevented OxLDL and H2O2-induced cytotoxicity, senescence, and inflammation in endothelial cells. Oral VCE-004.8 increased aorta sprouting in vitro and angiogenesis in vivo. In CLI mice VCE-004.8 improved collateral vessel formation and induced endothelial cells proliferation, angiogenic gene expression and prevented fibrosis. The expression of B55α, Caveolin 1 and Sirtuin-1 is reduced in arteries from CLI mice and PAD patient, and the expression of these markers was restored in mice treated with VCE-004.8. CONCLUSIONS: The findings presented in this study indicate that Etrinabdione holds promise in mitigating endothelial cell damage and senescence, while concurrently fostering arteriogenesis and angiogenesis. These observations position Etrinabdione as a compelling candidate for the treatment of PAD, and potentially other cardiovascular disorders.


Assuntos
Camundongos Endogâmicos C57BL , Neovascularização Fisiológica , Animais , Neovascularização Fisiológica/efeitos dos fármacos , Humanos , Masculino , Isquemia/patologia , Isquemia/tratamento farmacológico , Células Endoteliais da Veia Umbilical Humana/metabolismo , Camundongos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Biomarcadores/metabolismo , Proteômica , Angiogênese
14.
Glob Chang Biol ; 30(5): e17295, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38804108

RESUMO

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.


Assuntos
Embriófitas , Microbiota , Microbiologia do Solo , Biodiversidade , Solo/química
15.
Acta Psychiatr Scand ; 150(6): 543-561, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39243167

RESUMO

BACKGROUND: Functional recovery remains a core clinical objective for patients with bipolar disorder (BD). Sociodemographic, clinical, and neurocognitive variables are associated with long-term functional impairment, yet the impact of sex differences is unclear. Functional remediation (FR) is a validated intervention aimed at achieving functional recovery in BD. The present study assessed the effect of sex differences of FR on psychosocial functioning at post-treatment (6-months) and 12-month follow-up (FUP). To the best of our knowledge, this is the first study to explore the role of sex as a factor in the efficacy of FR. METHODS: 157 participants with BD were randomly assigned to either FR (N = 77) or treatment as usual group (80). Clinical, sociodemographic, neuropsychological, and functional data were obtained using a comprehensive assessment battery. Sex differences were explored via a general linear model (GLM) for repeated measures to compare the effect of sex on the intervention over time (6 months and FUP). RESULTS: Results demonstrated that FR benefits both sexes, males (p = 0.001; d' = 0.88) and females (p = 0.04; d' = 0.57), at 6 months suggesting a generalized functional improvement. Conversely, at 12-month FUP sex differences were observed only in males (p = 0.005; d' = 0.68). CONCLUSIONS: FR is a beneficial intervention for males and females after treatment, suggesting that there are no relevant distinct needs. Females may benefit from ongoing psychosocial functioning booster sessions after the intervention to maintain original improvements. Future research exploring sex differences could help to identify strategies to offer personalized FR intervention approaches in individuals with BD.

16.
Nanotechnology ; 35(28)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38522104

RESUMO

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).

17.
Phys Chem Chem Phys ; 26(13): 10183-10190, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38497123

RESUMO

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.

18.
Tob Control ; 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38378212

RESUMO

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.

19.
Artigo em Inglês | MEDLINE | ID: mdl-39377868

RESUMO

PURPOSE: To introduce a novel methodology for subjective refraction based on power vectors with a conventional phoropter. METHODS: A conventional phoropter was used to measure power vector components of refraction (M, J0 and J45) directly by using the sphere power (for M measurement) and the cylinder power combined with the Jackson cross-cylinders (for J0 and J45 measurements). Conventional subjective refraction was also performed, and this result was mathematically transformed into power vector notation for comparison purposes. Visual acuities with the conventional prescription and the quasi-vector-based prescription were compared. RESULTS: Refractive error from 40 healthy participants was measured by conventional and quasi-vector-based subjective refraction. No differences were found between methods for any of the power vector components of refraction (p > 0.21 in all cases). The visual acuity achieved with the prescriptions yielded similar values (p = 0.85). CONCLUSIONS: Subjective refraction can be measured directly in power vector notation using a conventional phoropter without any additional adaptation and computation.

20.
Ophthalmologica ; 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38493775

RESUMO

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.

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