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1.
Nature ; 617(7959): 111-117, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37100901

RESUMO

Tropical forests face increasing climate risk1,2, yet our ability to predict their response to climate change is limited by poor understanding of their resistance to water stress. Although xylem embolism resistance thresholds (for example, [Formula: see text]50) and hydraulic safety margins (for example, HSM50) are important predictors of drought-induced mortality risk3-5, little is known about how these vary across Earth's largest tropical forest. Here, we present a pan-Amazon, fully standardized hydraulic traits dataset and use it to assess regional variation in drought sensitivity and hydraulic trait ability to predict species distributions and long-term forest biomass accumulation. Parameters [Formula: see text]50 and HSM50 vary markedly across the Amazon and are related to average long-term rainfall characteristics. Both [Formula: see text]50 and HSM50 influence the biogeographical distribution of Amazon tree species. However, HSM50 was the only significant predictor of observed decadal-scale changes in forest biomass. Old-growth forests with wide HSM50 are gaining more biomass than are low HSM50 forests. We propose that this may be associated with a growth-mortality trade-off whereby trees in forests consisting of fast-growing species take greater hydraulic risks and face greater mortality risk. Moreover, in regions of more pronounced climatic change, we find evidence that forests are losing biomass, suggesting that species in these regions may be operating beyond their hydraulic limits. Continued climate change is likely to further reduce HSM50 in the Amazon6,7, with strong implications for the Amazon carbon sink.


Assuntos
Carbono , Florestas , Árvores , Clima Tropical , Biomassa , Carbono/metabolismo , Secas , Árvores/crescimento & desenvolvimento , Árvores/metabolismo , Xilema/metabolismo , Chuva , Mudança Climática , Sequestro de Carbono , Estresse Fisiológico , Desidratação
2.
Development ; 151(16)2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39037017

RESUMO

Following up on our previous observation that early B cell factor (EBF) sites are enriched in open chromatin of the developing sensory epithelium of the mouse cochlea, we investigated the effect of deletion of Ebf1 on inner ear development. We used a Cre driver to delete Ebf1 at the otocyst stage before development of the cochlea. We examined the cochlea at postnatal day (P) 1 and found that the sensory epithelium had doubled in size but the length of the cochlear duct was unaffected. We also found that deletion of Ebf1 led to ectopic sensory patches in the Kölliker's organ. Innervation of the developing organ of Corti was disrupted with no obvious spiral bundles. The ectopic patches were also innervated. All the extra hair cells (HCs) within the sensory epithelium and Kölliker's organ contained mechanoelectrical transduction channels, as indicated by rapid uptake of FM1-43. The excessive numbers of HCs were still present in the adult Ebf1 conditional knockout (cKO) animal. The animals had significantly elevated auditory brainstem response thresholds, suggesting that this gene is essential for hearing development.


Assuntos
Células Ciliadas Auditivas , Camundongos Knockout , Órgão Espiral , Transativadores , Animais , Transativadores/genética , Transativadores/metabolismo , Órgão Espiral/metabolismo , Células Ciliadas Auditivas/metabolismo , Camundongos , Surdez/genética , Deleção de Genes , Células Labirínticas de Suporte/metabolismo , Cóclea/metabolismo , Potenciais Evocados Auditivos do Tronco Encefálico
3.
EMBO J ; 41(23): e107257, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36314733

RESUMO

Plant immunity is tightly controlled by a complex and dynamic regulatory network, which ensures optimal activation upon detection of potential pathogens. Accordingly, each component of this network is a potential target for manipulation by pathogens. Here, we report that RipAC, a type III-secreted effector from the bacterial pathogen Ralstonia solanacearum, targets the plant E3 ubiquitin ligase PUB4 to inhibit pattern-triggered immunity (PTI). PUB4 plays a positive role in PTI by regulating the homeostasis of the central immune kinase BIK1. Before PAMP perception, PUB4 promotes the degradation of non-activated BIK1, while after PAMP perception, PUB4 contributes to the accumulation of activated BIK1. RipAC leads to BIK1 degradation, which correlates with its PTI-inhibitory activity. RipAC causes a reduction in pathogen-associated molecular pattern (PAMP)-induced PUB4 accumulation and phosphorylation. Our results shed light on the role played by PUB4 in immune regulation, and illustrate an indirect targeting of the immune signalling hub BIK1 by a bacterial effector.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Moléculas com Motivos Associados a Patógenos/metabolismo , Imunidade Vegetal/genética , Doenças das Plantas , Proteínas Serina-Treonina Quinases/genética
4.
Traffic ; 23(6): 331-345, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35426185

RESUMO

In the skin epidermis, melanin is produced and stored within melanosomes in melanocytes, and then transferred to keratinocytes. Different models have been proposed to explain the melanin transfer mechanism, which differ essentially in how melanin is transferred-either in a membrane-bound melanosome or as a melanosome core, that is, melanocore. Here, we investigated the endocytic route followed by melanocores and melanosomes during internalization by keratinocytes, by comparing the uptake of melanocores isolated from the supernatant of melanocyte cultures, with melanosomes isolated from melanocytes. We show that inhibition of actin dynamics impairs the uptake of both melanocores and melanosomes. Moreover, depletion of critical proteins involved in actin-dependent uptake mechanisms, namely Rac1, CtBP1/BARS, Cdc42 or RhoA, together with inhibition of Rac1-dependent signaling pathways or macropinocytosis suggest that melanocores are internalized by phagocytosis, whereas melanosomes are internalized by macropinocytosis. Interestingly, we found that Rac1, Cdc42 and RhoA are differently activated by melanocore or melanosome stimulation, supporting the existence of two distinct routes of melanin internalization. Furthermore, we show that melanocore uptake induces protease-activated receptor-2 (PAR-2) internalization by keratinocytes to a higher extent than melanosomes. Because skin pigmentation was shown to be regulated by PAR-2 activation, our results further support the melanocore-based mechanism of melanin transfer and further refine this model, which can now be described as coupled melanocore exo/phagocytosis.


Assuntos
Melaninas , Receptor PAR-2 , Actinas/metabolismo , Queratinócitos/metabolismo , Melaninas/metabolismo , Melanócitos/metabolismo , Melanossomas/metabolismo , Fagocitose/fisiologia , Receptor PAR-2/metabolismo
5.
Biochem Biophys Res Commun ; 696: 149514, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38237233

RESUMO

Organoselenium compounds modulate the metabolism by regulating carbohydrate and lipid syntheses and degradation in the liver, muscle, and adipose tissue. Notably, p-chloro-diphenyl diselenide (p-ClPhSe)2 can directly regulate the activities of enzymes involved in glucose metabolism, suggesting an insulin-like effect in rodents; however, there is still a lack of scientific evidence to confirm this hypothesis. The objective of this study was to investigate (p-ClPhSe)2 effects on glucose and lipid metabolism in Caenorhabditis elegans. The contribution of AGE-1/PI3K, AKT-1, AKT-2, PFK-1, DAF-16, and DAF-2 in the (p-ClPhSe)2 effects were also investigated. Our results demonstrate that (p-ClPhSe)2 acute exposure presented some toxicity to the worms, and therefore, lower concentrations were further used. (p-ClPhSe)2 reduced glucose and triglyceride levels to the baseline levels, after induction with glucose or fructose, in wild-type worms. This effect required proteins involved in the insulin/IGF-1 like signaling, such as the DAF-2, AGE-1, AKT-1 and AKT-2, PFK-1, but also DAF-16, which would be negatively regulated by DAF-2 activation. Moreover, the reduction in glucose and triglyceride levels, caused by (p-ClPhSe)2per se was lost in age-1/daf-16 worms, suggesting that insulin/IGF-1-like signaling in a DAF-2 and AGE-1/DAF-16 dependent-manner in C. elegans are necessary to effects of (p-ClPhSe)2. In conclusion, (p-ClPhSe)2 requires proteins involved in the IIS pathway to modulate carbohydrate and lipid metabolism.


Assuntos
Proteínas de Caenorhabditis elegans , Compostos Organosselênicos , Animais , Caenorhabditis elegans/metabolismo , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Metabolismo dos Lipídeos , Compostos Organosselênicos/farmacologia , Proteínas de Caenorhabditis elegans/metabolismo , Glucose/metabolismo , Triglicerídeos/metabolismo , Longevidade , Fatores de Transcrição Forkhead/metabolismo
6.
Breast Cancer Res Treat ; 206(2): 329-335, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38743176

RESUMO

PURPOSE: Circulating cell-free DNA (cfDNA) is a promising biomarker for predicting treatment response and disease outcomes in Breast Cancer (BC) patients undergoing neoadjuvant chemotherapy (NAC). To determine if cfDNA originates from tumors, matching tumor and cfDNA gene mutations are necessary, often requiring tumor DNA sequencing. We assessed plasma cfDNA integrity by measuring concentrations and ratios of larger-to-smaller Alu DNA fractions as a potential biomarker, eliminating the need for prior tumor sequencing. METHODS: We included patients with localized and/or locally advanced BC receiving standard NAC alone or in combination with immunotherapy and/or anti-HER2 targeted therapy. Blood samples were collected before treatment, every 2 weeks during treatment, and before surgery. RESULTS: Of the 38 evaluated patients, only 28 completed the protocol and underwent surgery after NAC. Seven patients (25%) achieved a pathologic complete response (pCR). We found that cfDNA integrity (cfDNAI) levels at 15 days after starting NAC were significantly higher in patients who achieved pCR (p = 0.045) and correlated significantly with Disease-Free Survival (DFS) in univariate analysis (p = 0.0371). CONCLUSIONS: Evaluation of cfDNAI 2 weeks after NAC initiation appears to be an early biomarker for tumor pCR and DFS. Measuring Alu fragments of different lengths may replace techniques requiring prior tumor sequencing to measure ctDNA, reducing costs and complexity of cfDNA serial measurements in BC patients undergoing NAC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais , Neoplasias da Mama , Ácidos Nucleicos Livres , Terapia Neoadjuvante , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Terapia Neoadjuvante/métodos , Biomarcadores Tumorais/sangue , Pessoa de Meia-Idade , Projetos Piloto , Adulto , Idoso , Ácidos Nucleicos Livres/sangue , Ácidos Nucleicos Livres/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Resultado do Tratamento , Prognóstico , Quimioterapia Adjuvante/métodos
7.
Org Biomol Chem ; 22(11): 2175-2181, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38259235

RESUMO

Herein, we report a KIO3-catalyzed oxidative coupling of thiols to their corresponding disulfides in water, in a short time and at ambient temperature. The reaction has a broad scope and exhibits good functional group tolerance, resulting in the desired products in excellent yields. This approach allows the reuse of the reaction system in multiple cycles and scale-up. Furthermore, the current protocol demonstrates compatibility for in situ generation of disulfides and post application in C(sp2)-H bond sulfenylation.

8.
J Comput Aided Mol Des ; 38(1): 21, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38693331

RESUMO

Covalent inhibition offers many advantages over non-covalent inhibition, but covalent warhead reactivity must be carefully balanced to maintain potency while avoiding unwanted side effects. While warhead reactivities are commonly measured with assays, a computational model to predict warhead reactivities could be useful for several aspects of the covalent inhibitor design process. Studies have shown correlations between covalent warhead reactivities and quantum mechanic (QM) properties that describe important aspects of the covalent reaction mechanism. However, the models from these studies are often linear regression equations and can have limitations associated with their usage. Applications of machine learning (ML) models to predict covalent warhead reactivities with QM descriptors are not extensively seen in the literature. This study uses QM descriptors, calculated at different levels of theory, to train ML models to predict reactivities of covalent acrylamide warheads. The QM/ML models are compared with linear regression models built upon the same QM descriptors and with ML models trained on structure-based features like Morgan fingerprints and RDKit descriptors. Experiments show that the QM/ML models outperform the linear regression models and the structure-based ML models, and literature test sets demonstrate the power of the QM/ML models to predict reactivities of unseen acrylamide warhead scaffolds. Ultimately, these QM/ML models are effective, computationally feasible tools that can expedite the design of new covalent inhibitors.


Assuntos
Cisteína , Desenho de Fármacos , Aprendizado de Máquina , Teoria Quântica , Cisteína/química , Acrilamida/química , Humanos , Modelos Moleculares , Relação Quantitativa Estrutura-Atividade , Modelos Lineares , Estrutura Molecular
9.
Curr Opin Ophthalmol ; 35(3): 225-231, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38484223

RESUMO

PURPOSE OF REVIEW: The field of corneal biomechanics has rapidly progressed in recent years, reflecting technological advances and an increased understanding of the clinical significance of measuring these properties. This review will evaluate in-vivo biomechanical properties obtained by current technologies and compare them regarding their relevance to established biomechanical properties obtained by gold-standard ex-vivo techniques normally conducted on elastic materials. RECENT FINDINGS: Several new technologies have appeared in recent years, including vibrational optical coherence tomography (VOCT) and the corneal indentation device (CID). These techniques provide promising new opportunities for minimally invasive and accurate measurements of corneal viscoelastic properties. SUMMARY: Alterations in corneal biomechanics are known to occur in several corneal degenerative diseases and after refractive surgical procedures. The measurement of corneal biomechanical properties has the capability to diagnose early disease and monitor corneal disease progression. Several new technologies have emerged in recent years, allowing for more accurate and less invasive measurements of corneal biomechanical properties, most notably the elastic modulus.


Assuntos
Doenças da Córnea , Procedimentos Cirúrgicos Refrativos , Humanos , Fenômenos Biomecânicos , Córnea/cirurgia , Tomografia de Coerência Óptica , Doenças da Córnea/cirurgia
10.
BMC Cardiovasc Disord ; 24(1): 21, 2024 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172786

RESUMO

BACKGROUND: Chronic kidney disease (CKD) and end-stage renal disease (ESRD) have been associated with worse outcomes after transcatheter aortic valve replacement (TAVR). With TAVR indications extending to a wider range of patient populations, it is important to understand the current implications of chronic renal insufficiency on clinical outcomes. We aim to determine the impact of CKD and ESRD on in-hospital outcomes after TAVR. METHODS: We queried the National Inpatient Sample for TAVR performed between 2016 and 2020 using International Classification of Diseases-10th Revision codes. We compared in-hospital mortality and clinical outcomes between three groups: normal renal function, CKD and ESRD. The association between CKD/ESRD and outcomes was tested with multivariable logistic regression analyses, using normal renal function as baseline. RESULTS: In the five-year study period, 279,195 patients underwent TAVR (mean age 78.9 ± 8.5 years, 44.4% female). Of all patients, 67.1% had normal renal function, 29.2% had CKD, and 3.7% had ESRD. There were significant differences in age, sex, and prevalence of comorbidities across groups. In-hospital mortality was 1.3%. Compared to patients with normal renal function, patients with renal insufficiency had higher in-hospital mortality, with the highest risk found in patients with ESRD (adjusted odds ratio: 1.4 [95% confidence interval: 1.2-1.7] for CKD; adjusted odds ratio: 2.4 [95% confidence interval: 1.8-3.3] for ESRD). Patients with CKD or ESRD had a higher risk of cardiogenic shock, need for mechanical circulatory support, and vascular access complications, compared to those with normal renal function. In addition, patients with ESRD had a higher risk of cardiac arrest and periprocedural acute myocardial infarction. The incidence of conversion to open heart surgery was 0.3% and did not differ between groups. Post-procedural infectious and respiratory complications were more common among patients with CKD or ESRD. CONCLUSION: Patients with CKD and ESRD are at higher risk of in-hospital mortality, cardiovascular, and non-cardiovascular complications after TAVR. The risk of complications is highest in patients with ESRD and does not result in more frequent conversion to open heart surgery. These results emphasize the importance of individualized patient selection for TAVR and procedural planning among patients with chronic renal insufficiency.


Assuntos
Estenose da Valva Aórtica , Falência Renal Crônica , Insuficiência Renal Crônica , Substituição da Valva Aórtica Transcateter , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Substituição da Valva Aórtica Transcateter/efeitos adversos , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Estenose da Valva Aórtica/complicações , Fatores de Risco , Resultado do Tratamento , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/terapia , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/terapia , Valva Aórtica/cirurgia
11.
J Med Genet ; 60(4): 317-326, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36849229

RESUMO

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome is a rare genetic syndrome caused by pathogenic or likely pathogenic germline variants in the FLCN gene. Patients with BHD syndrome have an increased risk of fibrofolliculomas, pulmonary cysts, pneumothorax and renal cell carcinoma. There is debate regarding whether colonic polyps should be added to the criteria. Previous risk estimates have mostly been based on small clinical case series. METHODS: A comprehensive review was conducted to identify studies that had recruited families carrying pathogenic or likely pathogenic variants in FLCN. Pedigree data were requested from these studies and pooled. Segregation analysis was used to estimate the cumulative risk of each manifestation for carriers of FLCN pathogenic variants. RESULTS: Our final dataset contained 204 families that were informative for at least one manifestation of BHD (67 families informative for skin manifestations, 63 for lung, 88 for renal carcinoma and 29 for polyps). By age 70 years, male carriers of the FLCN variant have an estimated 19% (95% CI 12% to 31%) risk of renal tumours, 87% (95% CI 80% to 92%) of lung involvement and 87% (95% CI 78% to 93%) of skin lesions, while female carriers had an estimated 21% (95% CI 13% to 32%) risk of renal tumours, 82% (95% CI 73% to 88%) of lung involvement and 78% (95% CI 67% to 85%) of skin lesions. The cumulative risk of colonic polyps by age 70 years old was 21% (95% CI 8% to 45%) for male carriers and 32% (95% CI 16% to 53%) for female carriers. CONCLUSIONS: These updated penetrance estimates, based on a large number of families, are important for the genetic counselling and clinical management of BHD syndrome.


Assuntos
Síndrome de Birt-Hogg-Dubé , Carcinoma de Células Renais , Pólipos do Colo , Neoplasias Renais , Humanos , Masculino , Feminino , Idoso , Síndrome de Birt-Hogg-Dubé/genética , Síndrome de Birt-Hogg-Dubé/patologia , Penetrância , Proteínas Proto-Oncogênicas/genética , Proteínas Supressoras de Tumor/genética , Neoplasias Renais/epidemiologia , Neoplasias Renais/genética , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/genética
12.
BMC Ophthalmol ; 24(1): 255, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38872120

RESUMO

BACKGROUND: Vitreoretinal lymphoma (VRL) is a rare intraocular malignancy that poses a diagnostic challenge due to the non-specific clinical presentation that resembles uveitis. The use of spectral domain optical coherence tomography (SD-OCT) has emerged as a valuable imaging tool to characterize VRL. Therefore, we sought to determine the specific OCT features in VRL compared to the uveitides. METHODS: Retrospective chart review of patients who were seen at Mayo Clinic from January 1, 2010 through December 31, 2022. The medical records and SD-OCT images at time of initial presentation were reviewed in patients with biopsy-proven VRL, intermediate uveitis, or biopsy-confirmed sarcoid posterior uveitis. Patients with VRL or similar uveitides including intermediate uveitis or sarcoid posterior uveitis were included. RESULTS: There were 95 eyes of 56 patients in the VRL group and 86 eyes of 45 patients in the uveitis group, of whom 15 (33.3%) were diagnosed with intermediate uveitis and 30 (66.7%) with sarcoid chorioretinitis. The SD-OCT features more commonly seen at initial presentation in VRL patients (vs. uveitis) included preretinal deposits (31.6% vs. 9.3%, p = 0.002), intraretinal infiltrates (34% vs. 3.5%, p < 0.001), inner retinal hyperreflective spots (15.8% vs. 0%, p < 0.001), outer retinal atrophy (22.1% vs. 2.3%, p < 0.001), subretinal focal deposits (21.1% vs. 4.7%, p = 0.001), retinal pigmented epithelium (RPE) changes (49.5% vs. 3.5%, p < 0.001), and sub-RPE deposits (34.7% vs. 0%, p < 0.001). Features more frequently seen in uveitis included epiretinal membrane (ERM) (82.6% vs. 44.2%, p < 0.001), central macular thickening (95.3% vs. 51.6%, p < 0.001), cystoid macular edema (36% vs. 11.7%, p < 0.001), subretinal fluid (16.3% vs 6.4%, p = 0.04), and subfoveal fluid (16.3% vs. 3.2%, p = 0.003). Multivariate regression analysis controlling for age and sex showed absence of ERM (OR 0.14 [0.04,0.41], p < 0.001) and absence of central macular thickening (OR 0.03 [0,0.15], p = 0.02) were associated with VRL as opposed to uveitis. CONCLUSION: OCT features most predictive of VRL (vs. uveitis) included absence of ERM and central macular thickening.


Assuntos
Neoplasias da Retina , Tomografia de Coerência Óptica , Uveíte , Corpo Vítreo , Humanos , Tomografia de Coerência Óptica/métodos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias da Retina/diagnóstico , Neoplasias da Retina/diagnóstico por imagem , Idoso , Corpo Vítreo/patologia , Corpo Vítreo/diagnóstico por imagem , Uveíte/diagnóstico , Adulto , Linfoma Intraocular/diagnóstico , Acuidade Visual , Diagnóstico Diferencial , Idoso de 80 Anos ou mais
13.
Nucleic Acids Res ; 50(16): 9279-9293, 2022 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-35979944

RESUMO

Metagenomics and total RNA sequencing (total RNA-Seq) have the potential to improve the taxonomic identification of diverse microbial communities, which could allow for the incorporation of microbes into routine ecological assessments. However, these target-PCR-free techniques require more testing and optimization. In this study, we processed metagenomics and total RNA-Seq data from a commercially available microbial mock community using 672 data-processing workflows, identified the most accurate data-processing tools, and compared their microbial identification accuracy at equal and increasing sequencing depths. The accuracy of data-processing tools substantially varied among replicates. Total RNA-Seq was more accurate than metagenomics at equal sequencing depths and even at sequencing depths almost one order of magnitude lower than those of metagenomics. We show that while data-processing tools require further exploration, total RNA-Seq might be a favorable alternative to metagenomics for target-PCR-free taxonomic identifications of microbial communities and might enable a substantial reduction in sequencing costs while maintaining accuracy. This could be particularly an advantage for routine ecological assessments, which require cost-effective yet accurate methods, and might allow for the incorporation of microbes into ecological assessments.


Assuntos
Metagenômica , Microbiota , Metagenômica/métodos , Microbiota/genética , Análise de Sequência de RNA , Sequenciamento de Nucleotídeos em Larga Escala/métodos , RNA Ribossômico 16S/genética
14.
An Acad Bras Cienc ; 96(3): e20230753, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38985031

RESUMO

The larynx is in the lower respiratory tract and has the function of protecting the airways, controlling, and modulating breathing, assisting the circulatory system, and vocalizing. This study aims to describe the anatomy and histology of the skeleton of the larynx and trachea of the species Chelonia mydas, Caiman yacare and Caiman latirostris. The study was conducted at the Federal University of Espírito Santo (UFES), using nine specimens of Ch. mydas, 20 of Ca. yacare and four of Ca. latirostris. Samples of the larynx and trachea were collected, fixed, and sent for dissection of the structures and subsequent macroscopic analysis. For histology, samples were processed by the routine paraffin embedding method and stained with hematoxylin-eosin and Verhoeff. For the three species, two arytenoid cartilages, a cricoid cartilage, a hyoid apparatus composed of a base and two horns were found. In Ch. mydas, two structures called thyroid wings were observed, not found in crocodilians. The trachea of crocodilians presented incomplete tracheal rings and musculature, while the trachea of Ch. mydas presented complete tracheal rings. Histologically, the entire cartilaginous skeleton of the larynx of the three species, as well as the tracheal rings, are constituted by hyaline cartilage.


Assuntos
Jacarés e Crocodilos , Laringe , Traqueia , Tartarugas , Animais , Traqueia/anatomia & histologia , Jacarés e Crocodilos/anatomia & histologia , Laringe/anatomia & histologia , Tartarugas/anatomia & histologia
15.
Arch Pharm (Weinheim) ; : e2400492, 2024 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-39074969

RESUMO

Drug repurposing is defined as the use of approved therapeutic drugs for indications different from those for which they were originally designed. Repositioning diminishes both the time and cost for drug development by omitting the discovery stage, the analysis of absorption, distribution, metabolism, and excretion routes, as well as the studies of the biochemical and physiological effects of a new compound. Besides, drug repurposing takes advantage of the increased bioinformatics knowledge and availability of big data biology. There are many examples of drugs with repurposed indications evaluated in in vitro studies, and in pharmacological, preclinical, or retrospective clinical analyses. Here, we briefly review some of the experimental strategies and technical advances that may improve translational research in cardiovascular diseases. We also describe exhaustive research from basic science to clinical studies that culminated in the final approval of new drugs and provide examples of successful drug repurposing in the field of cardiology.

16.
Altern Lab Anim ; 52(1): 60-68, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38061994

RESUMO

The Brazilian National Network of Alternative Methods (RENAMA), which is linked to the Ministry of Science, Technology and Innovation, is currently comprised of 51 laboratories from CROs, academia, industry and government. RENAMA's aim is to develop and validate new approach methodologies (NAMs), as well as train researchers and disseminate information on their use - thus reducing Brazilian, and consequently Latin American, dependence on external technology. Moreover, it promotes the adoption of NAMs by educators and trained researchers, as well as the implementation of good laboratory practice (GLP) and the use of certified products. The RENAMA network started its activities in 2012, and was originally comprised of three central laboratories - the National Institute of Metrology, Quality and Technology (INMETRO); the National Institute of Quality Control in Health (INCQS); and the National Brazilian Biosciences Laboratory (LNBio) - and ten associated laboratories. In 2022, RENAMA celebrated its 10th anniversary, a milestone commemorated by the organisation of a meeting attended by different stakeholders, including the RENAMA-associated laboratories, academia, non-governmental organisations and industry. Ninety-six participants attended the meeting, held on 26 May 2022 in Balneário Camboriú, SC, Brazil, as part of the programme of the XXIII Brazilian Congress of Toxicology 2022. Significant moments of the RENAMA were remembered, and new goals and discussion themes were established. The lectures highlighted recent innovations in the toxicological sciences that have translated into the assessment of consumer product safety through the use of human-relevant NAMs instead of the use of existing animal-based approaches. The challenges and opportunities in accepting such practices for regulatory purposes were also presented and discussed.


Assuntos
Aniversários e Eventos Especiais , Laboratórios , Animais , Humanos , Brasil
17.
Int J Mol Sci ; 25(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38791494

RESUMO

To investigate potential biomarkers and biological processes associated with diabetic retinopathy (DR) using transcriptomic and proteomic data. The OmicsPred PheWAS application was interrogated to identify genes and proteins associated with DR and diabetes mellitus (DM) at a false discovery rate (FDR)-adjusted p-value of <0.05 and also <0.005. Gene Ontology PANTHER analysis and STRING database analysis were conducted to explore the biological processes and protein interactions related to the identified biomarkers. The interrogation identified 49 genes and 22 proteins associated with DR and/or DM; these were divided into those uniquely associated with diabetic retinopathy, uniquely associated with diabetes mellitus, and the ones seen in both conditions. The Gene Ontology PANTHER and STRING database analyses highlighted associations of several genes and proteins associated with diabetic retinopathy with adaptive immune response, valyl-TRNA aminoacylation, complement activation, and immune system processes. Our analyses highlight potential transcriptomic and proteomic biomarkers for DR and emphasize the association of known aspects of immune response, the complement system, advanced glycosylation end-product formation, and specific receptor and mitochondrial function with DR pathophysiology. These findings may suggest pathways for future research into novel diagnostic and therapeutic strategies for DR.


Assuntos
Biomarcadores , Retinopatia Diabética , Inflamação , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Humanos , Inflamação/genética , Inflamação/metabolismo , Proteômica/métodos , Transcriptoma , Ontologia Genética , Mapas de Interação de Proteínas/genética , Perfilação da Expressão Gênica
18.
Molecules ; 29(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38338324

RESUMO

Consumers in developed and Western European countries are becoming more aware of the impact of food on their health, and they demand clear, transparent, and reliable information from the food industry about the products they consume. They recognise that food safety risks are often due to the unexpected presence of contaminants throughout the food supply chain. Among these, mycotoxins produced by food-infecting fungi, endogenous toxins from certain plants and organisms, pesticides, and other drugs used excessively during farming and food production, which lead to their contamination and accumulation in foodstuffs, are the main causes of concern. In this context, the goals of this review are to provide a comprehensive overview of the presence of toxic molecules reported in foodstuffs since 2020 through the Rapid Alert System for Food and Feed (RASFF) portal and use chromatography to address this challenge. Overall, natural toxins, environmental pollutants, and food-processing contaminants are the most frequently reported toxic molecules, and liquid chromatography and gas chromatography are the most reliable approaches for their control. However, faster, simpler, and more powerful analytical procedures are necessary to cope with the growing pressures on the food chain supply.


Assuntos
Micotoxinas , Toxinas Biológicas , Contaminação de Alimentos/análise , Micotoxinas/análise , Inocuidade dos Alimentos , Toxinas Biológicas/análise , Cromatografia Líquida , Abastecimento de Alimentos
19.
J Hist Dent ; 72(1): 48-51, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38642380

RESUMO

The evolution of 20-year-old dental museum-like showcases located in the lobby and the main hallway of the School of Dental Medicine, Puerto Rico (PR) are described along with important professionals who impacted on this development.


Assuntos
Faculdades de Medicina , Dente Impactado , Humanos , Adulto Jovem , Adulto , Porto Rico , Manobras Políticas , Museus
20.
J Hist Dent ; 72(1): 52-67, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38642381

RESUMO

The University of Puerto Rico School of Dentistry was established in 1957. Over the years, it has played an important role in Puerto Rico's healthcare system. That legacy is displayed through the walls of the School of Dentistry. In Part 1, the evolution of 20-year-old dental museum-like showcases located in the lobby and the main hallway of the school were described along with important professions who impacted on this development. In this paper, we will describe in detail the items available at the museum.


Assuntos
Atenção à Saúde , Instituições Acadêmicas , Porto Rico
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