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1.
Mol Cell ; 74(1): 73-87.e8, 2019 04 04.
Artigo em Inglês | MEDLINE | ID: mdl-30876805

RESUMO

The Hsp90 chaperone machinery in eukaryotes comprises a number of distinct accessory factors. Cns1 is one of the few essential co-chaperones in yeast, but its structure and function remained unknown. Here, we report the X-ray structure of the Cns1 fold and NMR studies on the partly disordered, essential segment of the protein. We demonstrate that Cns1 is important for maintaining translation elongation, specifically chaperoning the elongation factor eEF2. In this context, Cns1 interacts with the novel co-factor Hgh1 and forms a quaternary complex together with eEF2 and Hsp90. The in vivo folding and solubility of eEF2 depend on the presence of these proteins. Chaperoning of eEF2 by Cns1 is essential for yeast viability and requires a defined subset of the Hsp90 machinery as well as the identified eEF2 recruiting factor Hgh1.


Assuntos
Proteínas de Choque Térmico HSP90/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Chaperonas Moleculares/metabolismo , Elongação Traducional da Cadeia Peptídica , Fator 2 de Elongação de Peptídeos/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Cristalografia por Raios X , Peptidil-Prolil Isomerase F , Ciclofilinas/genética , Ciclofilinas/metabolismo , Proteínas de Choque Térmico HSP90/química , Proteínas de Choque Térmico HSP90/genética , Peptídeos e Proteínas de Sinalização Intracelular/química , Peptídeos e Proteínas de Sinalização Intracelular/genética , Modelos Moleculares , Chaperonas Moleculares/química , Chaperonas Moleculares/genética , Ressonância Magnética Nuclear Biomolecular , Fator 2 de Elongação de Peptídeos/química , Fator 2 de Elongação de Peptídeos/genética , Ligação Proteica , Dobramento de Proteína , Domínios e Motivos de Interação entre Proteínas , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Relação Estrutura-Atividade
2.
J Neurosci ; 44(23)2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38627089

RESUMO

According to the predictive processing framework, perception emerges from the reciprocal exchange of predictions and prediction errors (PEs) between hierarchically organized neural circuits. The nonlemniscal division of the inferior colliculus (IC) is the earliest source of auditory PE signals, but their neuronal generators, properties, and functional relevance have remained mostly undefined. We recorded single-unit mismatch responses to auditory oddball stimulation at different intensities, together with activity evoked by two sequences of alternating tones to control frequency-specific effects. Our results reveal a differential treatment of the unpredictable "many-standards" control and the predictable "cascade" control by lemniscal and nonlemniscal IC neurons that is not present in the auditory thalamus or cortex. Furthermore, we found that frequency response areas of nonlemniscal IC neurons reflect their role in subcortical predictive processing, distinguishing three hierarchical levels: (1) nonlemniscal neurons with sharply tuned receptive fields exhibit mild repetition suppression without signaling PEs, thereby constituting the input level of the local predictive processing circuitry. (2) Neurons with broadly tuned receptive fields form the main, "spectral" PE signaling system, which provides dynamic gain compensation to near-threshold unexpected sounds. This early enhancement of saliency reliant on spectral features was not observed in the auditory thalamus or cortex. (3) Untuned neurons form an accessory, "nonspectral" PE signaling system, which reports all surprising auditory deviances in a robust and consistent manner, resembling nonlemniscal neurons in the auditory cortex. These nonlemniscal IC neurons show unstructured and unstable receptive fields that could result from inhibitory input controlled by corticofugal projections conveying top-down predictions.


Assuntos
Estimulação Acústica , Percepção Auditiva , Colículos Inferiores , Colículos Inferiores/fisiologia , Animais , Estimulação Acústica/métodos , Masculino , Percepção Auditiva/fisiologia , Neurônios/fisiologia , Feminino , Vias Auditivas/fisiologia , Potenciais Evocados Auditivos/fisiologia , Macaca mulatta
3.
Appl Environ Microbiol ; 90(2): e0194823, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38193676

RESUMO

Deinococcus radiodurans exhibits remarkable survival under extreme conditions, including ionizing radiation, desiccation, and various DNA-damaging agents. It employs unique repair mechanisms, such as single-strand annealing (SSA) and extended synthesis-dependent strand annealing (ESDSA), to efficiently restore damaged genome. In this study, we investigate the role of the natural transformation-specific protein DprA in DNA repair pathways following acute gamma radiation exposure. Our findings demonstrate that the absence of DprA leads to rapid repair of gamma radiation-induced DNA double-strand breaks primarily occur through SSA repair pathway. Additionally, our findings suggest that the DprA protein may hinder both the SSA and ESDSA repair pathways, albeit in distinct manners. Overall, our results highlight the crucial function of DprA in the selection between SSA and ESDSA pathways for DNA repair in heavily irradiated D. radiodurans.IMPORTANCEDeinococcus radiodurans exhibits an extraordinary ability to endure and thrive in extreme environments, including exposure to radiation, desiccation, and damaging chemicals, as well as intense UV radiation. The bacterium has evolved highly efficient repair mechanisms capable of rapidly mending hundreds of DNA fragments in its genome. Our research indicates that natural transformation (NT)-specific dprA genes play a pivotal role in regulating DNA repair in response to radiation. Remarkably, we found that DprA is instrumental in selecting DNA double-strand break repair pathways, a novel function that has not been reported before. This unique regulatory mechanism highlights the indispensable role of DprA beyond its native function in NT and underscores its ubiquitous presence across various bacterial species, regardless of their NT proficiency. These findings shed new light on the resilience and adaptability of Deinococcus radiodurans, opening avenues for further exploration into its exceptional survival strategies.


Assuntos
Proteínas de Bactérias , Deinococcus , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Reparo do DNA , Quebras de DNA de Cadeia Dupla , DNA/metabolismo , Dano ao DNA , Deinococcus/genética , Deinococcus/metabolismo , DNA Bacteriano/genética , DNA Bacteriano/metabolismo
4.
Chemistry ; 30(30): e202400385, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38506412

RESUMO

77Se-NMR is used to characterise several chalcogen bonded complexes of derivatives of the organoselenium drug ebselen, exploring a range of electron demand. NMR titration experiments support the intuitive understanding that chalcogen bond donors bearing more electron withdrawing substituents give rise stronger chalcogen bonds. The chemical shift of the selenium nucleus is also shown to move upfield as it participates in a chalcogen bond. Solid-state NMR is used to explore chalcogen bonding in co-crystals. Due to the lack of molecular reorientation on the NMR timescale in the solid state, the shape of the chemical shift tensor can be determined using this technique. A range of co-crystals are shown to have extremely large chemical shift anisotropy, which suggests a strongly anisotropic electron density distribution around the selenium atom. A single crystal NMR experiment was conducted using one of the co-crystals, affording the absolute orientation of the chemical shift tensor within the crystal. This showed that the selenium nucleus is strongly shielded in the direction of the chalcogen bond (due to the approach of the lone pair of the Lewis base), and strongly deshielded in the perpendicular direction. The orientation of the deshielded axis is consistent with the presence of a second σ-hole which is not participating in a chalcogen bond, showing the profound effect of electron density anisotropy on the chemical shift.

5.
Rev Endocr Metab Disord ; 25(2): 383-398, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38051470

RESUMO

As the incidence of neuroendocrine tumors has been rising, gender differences in epidemiology and clinical behavior have emerged, and interest into a gender-driven management of these tumors has grown with the aim to improve survival and quality of life of these patients. Somatostatin Analogues represent the first line of systemic treatment of both functional and non-functional neuroendocrine tumors, through the expression of somatostatin receptors (SSTRs) in the tumor cells, and proved effective in controlling hormonal hypersecretion and inhibiting tumor growth, improving progression-free survival and overall survival of these patients. Aim of the present review is to investigate any differences by gender in efficacy and safety of SSTS-targeted therapies, that represent the mainstay treatment of neuroendocrine tumors, as they emerge from studies of varying design and intent. Although preclinical studies have provided evidence in favor of differences by gender in tumor expression of SSTR, as well as of the role of sex hormones and related receptors in modulating SSTRs expression and function, the clinical studies conducted so far have not shown substantial differences between males and females in either efficacy or toxicity of SSTR-targeted therapies, even if with sometimes inconsistent results. Moreover, in most studies gender was not a predictor of response to treatment. Studies specifically designed to address this issue are needed to develop gender-specific therapeutic algorithms, improving patients' prognosis and quality of life.


Assuntos
Tumores Neuroendócrinos , Somatostatina , Masculino , Feminino , Humanos , Somatostatina/uso terapêutico , Tumores Neuroendócrinos/patologia , Qualidade de Vida , Receptores de Somatostatina/metabolismo
6.
Lupus ; 33(7): 685-692, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38571373

RESUMO

OBJECTIVE: The aim of this study was to explore the parents' experiences of home monitoring of the fetal heart rhythm. Women with anti-SSA/Ro52 autoantibodies carry a 2%-3% risk of giving birth to a child with congenital heart block (CHB), following transplacental transfer and antibody-mediated inflammation in the fetal conduction system during 18th to 24th gestational week. Early detection and subsequent treatment have been reported to decrease morbidity and mortality. Therefore, home monitoring of the fetal heart rhythm by Doppler has been offered at our fetal cardiology center. This study was undertaken to explore the lived experience of the routine. METHODS: Participants were recruited from a single fetal cardiology center. Consecutive sampling was used. The inclusion criteria were women with SSA/Ro52 antibodies who had undergone Doppler examinations within the last two and a half years at the hospital and had monitored the fetal heartbeat at home. A semi-structured questionnaire was created, and the participants were interviewed individually. The interviews were transcribed verbatim and analyzed according to qualitative content analysis. RESULTS: The overall theme was defined as "walking on thin ice," with six underlying categories: reality, different strategies, gain and loss, healthcare providers, underlying tension, and conducting the examinations again, all with a focus on how to handle the home monitoring during the risk period. CONCLUSION: Both the mother and the co-parent expressed confidence in their own abilities and that the monitoring provided them with the advantage of growing a bond with the expected child. However, all the participants described a feeling of underlying tension during the risk period. The results show that home monitoring is not experienced as complicated or a burden for the parents-to-be and should be considered a vital part of the chain of care for mothers at risk for giving birth to a child with CHB. However, explaining the teamwork between the different caregivers, for the patients involved, their areas of expertise, and how they collaborate with the patient continues to be a pedagogic challenge and should be developed further.


Assuntos
Anticorpos Antinucleares , Bloqueio Cardíaco , Frequência Cardíaca Fetal , Pais , Humanos , Feminino , Gravidez , Adulto , Pais/psicologia , Bloqueio Cardíaco/congênito , Bloqueio Cardíaco/imunologia , Bloqueio Cardíaco/diagnóstico , Anticorpos Antinucleares/sangue , Autoanticorpos/sangue , Inquéritos e Questionários , Masculino , Ribonucleoproteínas/imunologia , Monitorização Fetal/métodos
7.
BMC Infect Dis ; 24(1): 347, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521947

RESUMO

BACKGROUND: Men who have sex with men (MSM) are a key population group disproportionately affected by HIV and other sexually transmitted infections (STIs) worldwide. In Rwanda, the HIV epidemic remains a significant public health concern, and understanding the burden of HIV and hepatitis B and C coinfections among MSM is crucial for designing effective prevention and control strategies. This study aims to determine the prevalence of HIV, hepatitis B, and hepatitis C infections among MSM in Rwanda and identify correlates associated with HIV infection within this population. METHODS: We used respondent-driven sampling (RDS) to recruit participants between November and December 2021. A face-to-face, structured questionnaire was administered. Testing for HIV infection followed the national algorithm using two rapid tests: Alere Combo and STAT PAK as the first and second screening tests, respectively. Hepatitis B surface antigen (HBsAg) and anti-HCV tests were performed. All statistics were adjusted for RDS design, and a multivariable logistic regression model was constructed to identify factors associated with HIV infection. RESULTS: The prevalence of HIV among MSM was 6·9% (95% CI: 5·5-8·6), and among HIV-positive MSM, 12·9% (95% CI: 5·5-27·3) were recently infected. The prevalence of hepatitis B and C was 4·2% (95% CI: 3·0-5·7) and 0·7% (95% CI: 0·4-1·2), respectively. HIV and hepatitis B virus coinfection was 0·5% (95% CI: 0·2-1·1), whereas HIV and hepatitis C coinfection was 0·1% (95% CI: 0·0-0·5), and no coinfection for all three viruses was observed. MSM groups with an increased risk of HIV infection included those who ever suffered violence or abuse because of having sex with other men (AOR: 3·42; 95% CI: 1·87-6·25), those who refused to answer the question asking about 'ever been paid money, goods, or services for sex' (AOR: 10·4; 95% CI: 3·30-32·84), and those not consistently using condoms (AOR: 3·15; 95% CI: 1·31-7·60). CONCLUSION: The findings suggest more targeted prevention and treatment approaches and underscore the importance of addressing structural and behavioral factors contributing to HIV vulnerability, setting interventions to reduce violence and abuse against MSM, promoting safe and consensual sexual practices, and expanding access to HIV prevention tools such as condoms and preexposure prophylaxis (PrEP).


Assuntos
Coinfecção , Infecções por HIV , Hepatite B , Hepatite C , Minorias Sexuais e de Gênero , Masculino , Humanos , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Infecções por HIV/diagnóstico , Homossexualidade Masculina , Coinfecção/epidemiologia , Estudos Transversais , Ruanda/epidemiologia , Fatores de Risco , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Inquéritos e Questionários , Prevalência
8.
J Cutan Pathol ; 51(4): 317-326, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38158735

RESUMO

BACKGROUND: In dermatomyositis (DM), myositis-specific and myositis-associated antibodies have been correlated with clinical features. It is unknown if histopathologic findings in lesional skin biopsies correlate with serologic subtypes of DM. METHODS: A retrospective chart review of patients with DM was performed. Patients with myositis antibodies and DM lesional skin biopsies were included in the study. Skin biopsies were reviewed by blinded dermatopathologists for 20 histopathologic features. RESULTS: There was a statistically significant (p < 0.05) association between anti-PL-7 serology and decreased degree of vacuolar degeneration, necrotic keratinocytes, and thickening of the epidermal basement membrane. Anti-aminoacyl tRNA synthetase (anti-ARS) antibodies had the same significant negative association with degree of vacuolar degeneration, necrotic keratinocytes, and thickening of the epidermal basement membrane. A similar pattern was seen with an anti-cytoplasmic serology; where there was a significant association with an increased degree of vacuolar degeneration and necrotic keratinocytes, and a nonsignificant trend of minimally thickened epidermal basement membrane. There was a statistically significant association between anti-Ro/SSA serology and increased degree of vacuolar degeneration. Anti-TIF1-γ serology was significantly associated with the increased presence of necrotic keratinocytes and pigment incontinence, and displayed a pattern of increased neutrophils. There was a significant association between anti-Mi-2 antibodies and pigment incontinence, as well as between myositis-specific antibodies and pigment incontinence. A statistically significant positive association was found between nuclear antibodies and degree of vacuolar degeneration, thickened epidermal basement membrane, pigment incontinence, and epidermal atrophy. CONCLUSION: In patients with DM, some specific serotypes, including anti-PL-7, anti-Ro/SSA, anti-Mi-2, and anti-TIF1-γ, may have characteristic histopathologic features.


Assuntos
Dermatomiosite , Doenças Pulmonares Intersticiais , Miosite , Humanos , Dermatomiosite/complicações , Estudos Retrospectivos , Miosite/complicações , Autoanticorpos
9.
Eur J Pediatr ; 183(1): 149-155, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37848593

RESUMO

This study aims to analyze the clinical characteristics and risk factors of high-risk groups of neonatal lupus erythematosus (NLE) in term infants. High-risk groups of NLE infants whose mothers were positive for anti-SSA, anti-SSB or anti-U1RNP antibodies during pregnancy were enrolled. They were born between February 2013 and February 2020, with a gestational age not less than 37 weeks. We analyzed their clinical data from birth to 24 months after birth. A total of 105 patients in the NLE high-risk group were included. Among them, 30 patients were diagnosed with NLE (NLE group), and 75 patients were not (non-NLE group). The affected systems of the NLE group included the dermal (13.3%), hepatic (76.0%), and hematological systems (43.3%). Hepatic involvement, anemia and thrombocytopenia did not emerge until 60 days, 41 days and 22 days after birth, respectively, in some cases. Systemic involvement could be cured within 3 to 12 months after birth. The clearance time of specific autoantibodies was 12 months after birth. There was no significant difference in the clinical characteristics of babies and their mothers between the two groups, neither in the positive rate nor in the clearance time of specific autoantibodies. CONCLUSION: After standardized prenatal health care, there is still a high risk of dermal, hepatic, or hematological system involvement for high-risk groups of NLE. There are no specific indicators for the prediction of whether babies will develop NLE. All of these patients need to be followed up closely within one year after birth. WHAT IS KNOWN: • Neonatal lupus erythematosus (NLEs) can affect the cardiac, dermal, hepatic, and hematological systems of infants. WHAT IS NEW: • After standardized prenatal health care employing good multidepartment cooperation in our center, no neonates had cardiac block in this study. However, dermal, hepatic, and hematological system involvement of NLE can still gradually appear (as long as 60 days after birth in some cases) during follow-up, and some of these conditions are serious and require timely and active intervention. No single factor has been found to predict whether offspring at high-risk of NLE whose mothers are positive for anti-SSA, SSB and/or RNP will develop NLE.


Assuntos
Lúpus Eritematoso Cutâneo , Lúpus Eritematoso Sistêmico , Lúpus Eritematoso Sistêmico/congênito , Feminino , Gravidez , Lactente , Recém-Nascido , Humanos , Estudos de Coortes , Lúpus Eritematoso Cutâneo/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Autoanticorpos , Anticorpos Antinucleares
10.
BMC Pregnancy Childbirth ; 24(1): 8, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166935

RESUMO

BACKGROUND: Contraceptive use is a key indicator of improving the health and well-being of women, mothers and their families, preventing unwanted pregnancies, and reducing maternal and child mortalities. Despite a lot of investments from the Government of Guinea to improve contraceptive use, studies reveal that contraceptive use still remains low in Guinea. However, the intention to use contraceptives in Guinea has not been well examined. Therefore, this study seeks to examine the factors associated with the intention to use contraceptives among women of reproductive age in Guinea. METHODS: The study made use of data from the Guinea Demographic and Health Survey (GNDHS) conducted in 2018. For this study, we included a weighted sample of 6,948 women who were either married or cohabiting and responded to all the variables of interest. The data were analyzed using Stata version 14.2. Descriptive and multilevel logistic regression were carried out to examine the factors associated with the intention to use contraceptives. The results of multilevel logistic regression were presented using adjusted odds ratios at 95% confidence intervals and p-value < 0.05 to determine the significant associations. RESULTS: The prevalence of intention-to-use contraceptives among women was 19.8% (95% CI18.3%-21.5%). Women with secondary/higher educational levels [aOR = 1.58, 95% CI = 1.26-1.99], women whose partners had secondary/higher educational level [aOR = 1.26, 95% CI = 1.04-1.52], women who were cohabiting [aOR = 1.74, 95% CI = 1.13-2.68] and were exposed to mass media [aOR = 1.60, 95% CI = 1.35-1.89] were likely to have higher intentions to use contraceptives. Additionally, women from the Kankan Region [aOR = 4.26, 95% CI = 2.77-6.54] and women who belong to the richer wealth quintile [aOR = 1.36, 95% CI = 0.91-1.89] were likely to have higher odds of intentions to use contraceptives. However, women aged 45-49 years, those from the Peulh ethnic group, and those who lack the competence to make healthcare decisions alone had lower odds of intention to use contraceptives. CONCLUSION: The study revealed a low prevalence of intention to use contraceptives among women of reproductive age in Guinea. The study has highlighted that both individual-level and household/community-level factors were significantly associated with the intention to use contraceptives. Therefore, policymakers and stakeholders need to consider these factors discussed in this paper when developing policies and interventions to promote and enhance intention-to-use contraceptives among women of reproductive age in Guinea. The findings call on the Government of Guinea and all stakeholders in Guinea to ensure that female education is promoted to help improve their social status, decision-making on fertility, and reduce fertility rates and maternal mortality.


Assuntos
Anticoncepcionais , Intenção , Gravidez , Criança , Feminino , Humanos , Análise Multinível , Prevalência , Guiné/epidemiologia , Casamento , Comportamento Contraceptivo
11.
BMC Public Health ; 24(1): 1631, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898450

RESUMO

BACKGROUND: The world health organization's global health observatory defines maternal mortality as annual number of female deaths, regardless of the period or location of the pregnancy, from any cause related to or caused by pregnancy or its management (aside from accidental or incidental causes) during pregnancy and childbirth or within 42 days of termination of pregnancy and an estimated 287 000 women worldwide passed away from maternal causes between 2016 and 2020, that works out to be about 800 deaths per day or about one every two minutes. METHOD: The most recent 2018-2023 DHS data set of 14 SSA countries was used a total of 89,489 weighted mothers who gave at list one live birth 3 years preceding the survey were included, a multilevel analysis was conducted. In the bi-variable analysis variables with p-value ≤ 0.20 were included in the multivariable analysis, and in the multivariable analysis, variables with p-value less than ≤ 0.05 were considered to be significant factors associated with having eight and more ANC visits. RESULT: The magnitude of having eight and more ANC visits in 14 sub-Saharan African countries was 8.9% (95% CI: 8.76-9.13) ranging from 3.66% (95% CI: 3.54-3.79) in Gabon to 18.92% (95% CI: 18.67-19.17) in Nigeria. The multilevel analysis shows that maternal age (40-44, AOR;2.09, 95%CI: 1.75-2.53), maternal occupational status (AOR;1.14, 95%CI; 1.07-1.22), maternal educational level (secondary and above, AOR;1.26, 95%CI; 1.16-1.38), wealth status(AOR;1.65, 95%CI; 1.50-1.82), media exposure (AOR;1.20, 95%CI; 1.11-1.31), pregnancy intention (AOR;1.12, 95%CI; 1.05-1.20), ever had terminated pregnancy (AOR;1.16 95%CI; 1.07-1.25), timely initiation of first ANC visit (AOR;4.79, 95%CI; 4.49-5.10), empowerment on respondents health care (AOR;1.43, 95%CI; 1.30-1.56), urban place of residence (AOR;1.33, 95%CI; 1.22-1.44) were factors highly influencing the utilization of AN. On the other hand higher birth order (AOR;0.54, 95%CI; 0.53-0.66), not using contraceptive (AOR;0.80, 95%CI; 0.75-0.86) and survey year (AOR;0.47, 95%CI; 0.34-0.65) were factors negatively associated with having eight and more ANC visits. CONCLUSION: In the 14 SSA included in this study, there is low adherence to WHO guidelines of eight and more ANC visits. Being educated, having jobs, getting access to media being from rural residence and rich wealth group contribute to having eight and more ANC visits, so we highly recommend policy implementers to advocate this practices.


Assuntos
Análise Multinível , Cuidado Pré-Natal , Humanos , Feminino , Adulto , África Subsaariana , Adulto Jovem , Gravidez , Cuidado Pré-Natal/estatística & dados numéricos , Adolescente , Pessoa de Meia-Idade , Mães/estatística & dados numéricos , Mães/psicologia
12.
Chem Pharm Bull (Tokyo) ; 72(4): 365-373, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38569867

RESUMO

Obesity is known to be associated with increased inflammation and dysregulated autophagy, both of which contribute to insulin resistance. Saikosaponin-A (SSA) has been reported to exhibit anti-inflammatory and lipid-lowering properties. In this research, we employed a combination of computational modeling and animal experiments to explore the effects of SSA. Male C57BL/6 mice were categorized into four groups: normal diet, high-fat diet (HFD), HFD + atorvastatin 10 mg/kg, and HFD + SSA 10 mg/kg. We conducted oral glucose and fat tolerance tests to assess metabolic parameters and histological changes. Furthermore, we evaluated the population of Kupffer cells (KCs) and examined gene expressions related to inflammation and autophagy. Computational analysis revealed that SSA displayed high binding affinity to tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, fibroblast growth factor 21 (FGF21), and autophagy-related 7 (ATG7). Animal study demonstrated that SSA administration improved fasting and postprandial glucose levels, homeostatic model assessment of insulin resistance (HOMA-IR) index, as well as triglyceride, free fatty acid, total cholesterol, low-density lipoprotein cholesterol (LDL-C)-cholesterol, and high-density lipoprotein cholesterol (HDL-C)-cholesterol levels in HFD-fed mice. Moreover, SSA significantly reduced liver weight and fat accumulation, while inhibiting the infiltration and M1 activation of KCs. At the mRNA level, SSA downregulated TNF-α and NF-κB expression, while upregulating FGF21 and ATG7 expression. In conclusion, our study suggests that SSA may serve as a therapeutic agent for addressing the metabolic complications associated with obesity. This potential therapeutic effect is attributed to the suppression of inflammatory cytokines and the upregulation of FGF21 and ATG7.


Assuntos
Experimentação Animal , Resistência à Insulina , Ácido Oleanólico/análogos & derivados , Saponinas , Camundongos , Masculino , Animais , Resistência à Insulina/fisiologia , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Fígado , Inflamação/metabolismo , Glucose/metabolismo , Colesterol , Dieta Hiperlipídica/efeitos adversos , Fator de Necrose Tumoral alfa/metabolismo , Insulina/metabolismo
13.
Sensors (Basel) ; 24(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38676213

RESUMO

The Stingray sensor system is a 15-camera optical array dedicated to the nightly astrometric and photometric survey of the geosynchronous Earth orbit (GEO) belt visible above Tucson, Arizona. The primary scientific goal is to characterize GEO and near-GEO satellites based on their observable properties. This system is completely autonomous in both data acquisition and processing, with human oversight reserved for data quality assurance and system maintenance. The 15 ZWO ASI1600MM Pro cameras are mated to Sigma 135 mm f/1.8 lenses and are controlled simultaneously by four separate computers. Each camera is fixed in position and observes a 7.6-by-5.8-degree portion of the GEO belt, for a total of a 114-by-5.8-degree field of regard. The GAIA DR2 star catalog is used for image astrometric plate solution and photometric calibration to GAIA G magnitudes. There are approximately 200 near-GEO satellites on any given night that fall within the Stingray field of regard, and all those with a GAIA G magnitude brighter than approximately 15.5 are measured by the automated data reduction pipeline. Results from an initial one-month survey show an aggregate photometric uncertainty of 0.062 ± 0.008 magnitudes and astrometric accuracy consistent with theoretical sub-pixel centroid limits. Provided in this work is a discussion of the design and function of the system, along with verification of the initial survey results.

14.
Sensors (Basel) ; 24(4)2024 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-38400337

RESUMO

Satellite clock error is a key factor affecting the positioning accuracy of a global navigation satellite system (GNSS). In this paper, we use a gated recurrent unit (GRU) neural network to construct a satellite clock bias forecasting model for the BDS-3 navigation system. In order to further improve the prediction accuracy and stability of the GRU, this paper proposes a satellite clock bias forecasting model, termed ITSSA-GRU, which combines the improved sparrow search algorithm (SSA) and the GRU, avoiding the problems of GRU's sensitivity to hyperparameters and its tendency to fall into local optimal solutions. The model improves the initialization population phase of the SSA by introducing iterative chaotic mapping and adopts an iterative update strategy based on t-step optimization to enhance the optimization ability of the SSA. Five models, namely, ITSSA-GRU, SSA-GRU, GRU, LSTM, and GM(1,1), are used to forecast the satellite clock bias data in three different types of orbits of the BDS-3 system: MEO, IGSO, and GEO. The experimental results show that, as compared with the other four models, the ITSSA-GRU model has a stronger generalization ability and forecasting effect in the clock bias forecasting of all three types of satellites. Therefore, the ITSSA-GRU model can provide a new means of improving the accuracy of navigation satellite clock bias forecasting to meet the needs of high-precision positioning.

15.
Sensors (Basel) ; 24(8)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38676209

RESUMO

Detecting gear rim fatigue cracks using vibration signal analysis is often a challenging task, which typically requires a series of signal processing steps to detect and enhance fault features. This task becomes even harder in helicopter planetary gearboxes due to the complex interactions between different gear sets and the presence of vibration from sources other than the planetary gear set. In this paper, we propose an effectual processing algorithm to isolate and enhance rim crack features and to trend crack growth in planet gears. The algorithm is based on using cepstrum editing (or liftering) of the hunting-tooth synchronous averaged signals (angular domain) to extract harmonics and sidebands of the planet gears and low-pass filtering and minimum entropy deconvolution (MED) to enhance extracted fault features. The algorithm has been successfully applied to a vibration dataset collected from a planet gear rim crack propagation test undertaken in the Helicopter Transmission Test Facility (HTTF) at DSTG Melbourne. In this test, a seeded notch generated by an electric discharge machine (EDM) was used to initiate a fatigue crack that propagated through the gear rim body over 94 load cycles. The proposed algorithm demonstrated a successful isolation of incipient fault features and provided a reliable trending capability to monitor crack progression. Results of a comparative analysis showed that the proposed algorithm outperformed the traditional signal processing approach.

16.
Sensors (Basel) ; 24(8)2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38676251

RESUMO

With the acceleration of urbanisation, urban areas are subject to the combined effects of the accumulation of various natural factors, such as changes in temperature leading to the thermal expansion or contraction of surface materials (rock, soil, etc.) and changes in precipitation and humidity leading to an increase in the self-weight of soil due to the infiltration of water along the cracks or pores in the ground. Therefore, the subsidence of urban areas has now become a serious geological disaster phenomenon. However, the use of traditional neural network prediction models has limitations when examining the causal relationships between time series surface deformation data and multiple influencing factors and when applying multiple influencing factors for predictive analyses. To this end, Sentinel-1A data from March 2017 to February 2023 were used as the data source in this paper, based on time series deformation data acquired using the small baseline subset interferometric synthetic aperture radar (SBAS-InSAR) technique. A sparrow search algorithm-convolutional neural network-long short-term memory (SSA-CNN-LSTM) neural network prediction model was built. The six factors of temperature, humidity, precipitation, and ground temperature at three different depths below the surface (5 cm, 10 cm, and 15 cm) were taken as the input of the model, and the surface deformation data were taken as the output of the neural network model. The correlation between the spatial and temporal evolution characteristics of the ground subsidence in urban areas and various influencing factors was analysed using grey correlation analysis, which proved that these six factors contribute to some extent to the deformation of the urban surface. The main urban area of Hohhot City, Inner Mongolia Autonomous Region, was used as the study area. In order to verify the efficacy of this neural network prediction model, the prediction effects of the multilayer perceptron (MLP), backpropagation (BP), and SSA-CNN-LSTM models were compared and analysed, with the values of the correlation coefficients of the feature points of A1, B1, and C1 being in the range of 0.92, 0.83, and 0.93, respectively. The results show that compared with the traditional MLP and BP neural network models, the SSA-CNN-LSTM model achieves a higher performance in predicting time series surface deformation data in urban areas, which provides new ideas and methods for this area of research.

17.
J Sci Food Agric ; 2024 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-38808632

RESUMO

BACKGROUND: The total volatile basic nitrogen (TVB-N) is the main indicator for evaluating the freshness of fish meal, and accurate detection and monitoring of TVB-N is of great significance for the health of animals and humans. Here, to realize fast and accurate identification of TVB-N, in this article, a self-developed electronic nose (e-nose) was used, and the mapping relationship between the gas sensor response characteristic information and TVB-N value was established to complete the freshness detection. RESULTS: The TVB-N variation curve was decomposed into seven subsequences with different frequency scales by means of variational mode decomposition (VMD). Each subsequence was modelled using different long short-term memory (LSTM) models, and finally, the final TVB-N prediction result was obtained by adding the prediction results based on different frequency components. To improve the performance of the LSTM, the sparrow search algorithm (SSA) was used to optimize the number of hidden units, learning rate and regularization coefficient of LSTM. The prediction results indicated that the high accuracy was obtained by the VMD-LSTM model optimized by SSA in predicting TVB-N. The coefficient of determination (R2), the root-mean-squared error (RMSE) and relative standard deviation (RSD) between the predicted value and the actual value of TVBN were 0.91, 0.115 and 6.39%, respectively. CONCLUSIONS: This method improves the performance of e-nose in detecting the freshness of fish meal and provides a reference for the quality detection of e-nose in other materials. © 2024 Society of Chemical Industry.

18.
J Neurosci ; 42(8): 1454-1476, 2022 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-34949693

RESUMO

Sensory experience during a critical period alters sensory cortical responses and organization. We find that the earliest sound-driven activity in the mouse auditory cortex (ACX) starts before ear-canal opening (ECO). The effects of auditory experience before ECO on ACX development are unknown. We find that in mouse ACX subplate neurons (SPNs), crucial in thalamocortical maturation, respond to sounds before ECO showing oddball selectivity. Before ECO, SPNs are more selective to oddball sounds in auditory streams than thalamo-recipient layer 4 (L4) neurons and not after ECO. We hypothesize that SPN's oddball selectivity can direct the development of L4 responses before ECO. Exposing mice, of either sex, before ECO to a rarely occurring tone in a stream of another tone occurring frequently leads to strengthening the adult cortical representation of the rare tone, but not that of the frequent tone. Results of control exposure experiments at multiple developmental windows that also use only a single tone corroborate the observations. We further explain the strengthening of deviant inputs before ECO and not after ECO using a binary network model mimicking the hierarchical structure of subplate and L4 neurons and response properties derived from our data, with synapses following Hebbian spike time-dependent plasticity learning rule. Information-theoretic analysis with sparse coding assumptions also predicts the observations. Thus, relatively salient low probability sounds in the earliest auditory environment cause long-term changes in the ACX.SIGNIFICANCE STATEMENT Early auditory experience can change the organization and responses of the auditory cortex in adulthood. However, little is known about how auditory experience at prenatal ages changes neural circuits and response properties. In mice at equivalent early developmental stages, we find that auditory experience of a particular kind, with a less frequently occurring sound in a stream of another sound, alters adult cortical responsiveness, specifically of the less frequent sound. However, at the previously known critical period of development, the opposite is observed, where the more frequent sound's representation is strengthened in the adult compared with the less frequent sound. We thus show that a specific type of auditory environment can influence adult auditory processing at the earliest ages.


Assuntos
Córtex Auditivo , Estimulação Acústica/métodos , Animais , Córtex Auditivo/fisiologia , Percepção Auditiva/fisiologia , Camundongos , Neurônios/fisiologia , Som , Sinapses/fisiologia
19.
J Neurosci ; 42(15): 3165-3183, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35241488

RESUMO

Auditory cortex (ACX) neurons are sensitive to spectro-temporal sound patterns and violations in patterns induced by rare stimuli embedded within streams of sounds. We investigate the auditory cortical representation of repeated presentations of sequences of sounds with standard stimuli (common) with an embedded deviant (rare) stimulus in two conditions, Periodic (Fixed deviant position) or Random (Random deviant position). We used extracellular single-unit and two-photon Ca2+ imaging recordings in layer 2/3 neurons of the mouse (Mus musculus) ACX of either sex. Population single-unit average responses increased over repetitions in the Random condition and were suppressed or did not change in the Periodic condition, showing general irregularity preference. A subset of neurons showed the opposite behavior, indicating regularity preference. Furthermore, pairwise noise correlations were higher in the Random condition than in the Periodic condition, suggesting a role of recurrent connections in the observed differential adaptation. Functional two-photon Ca2+ imaging showed that excitatory (EX), and inhibitory (IN) neurons [parvalbumin-positive (PV) and somatostatin-positive (SOM)] also had different categories of long-term adaptation as observed with single-units. However, examination of functional connectivity between pairs of neurons of different categories showed that EX-PV connected pairs behaved opposite to the EX-EX and EX-SOM pairs, with more connections outside category in Random condition than Periodic condition. Finally, considering Regularity, Irregularity, and no preference of connected pairs of neurons showed that EX-EX and EX-SOM pairs were in largely separate functional subnetworks with different preferences, not EX-PV pairs. Thus, separate subnetworks underlie coding of periodic and random sound sequences.SIGNIFICANCE STATEMENT Studying how the auditory cortex (ACX) neurons respond to streams of sound sequences help us understand the importance of changes in dynamic acoustic noisy scenes around us. Humans and animals are sensitive to regularity and its violations in sound sequences. Psychophysical tasks in humans show that the auditory brain differentially responds to Periodic and Random structures, independent of the listener's attentional states. Here, we show that mouse ACX L2/3 neurons detect changes and respond differently to patterns over long-time scales. The differential functional connectivity profile obtained in response to two different sound contexts suggests the vital role of recurrent connections in the auditory cortical network. Furthermore, the excitatory-inhibitory neuronal interactions can contribute to detecting the changing sound patterns.


Assuntos
Córtex Auditivo , Estimulação Acústica/métodos , Animais , Córtex Auditivo/fisiologia , Percepção Auditiva/fisiologia , Camundongos , Neurônios/fisiologia , Ruído , Parvalbuminas/metabolismo , Som
20.
BMC Cancer ; 23(1): 148, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36782152

RESUMO

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of tumors with a broad range of local and systemic treatment options. Still a lack of data regarding treatment sequences exists. The aim of this study was to analyse outcomes in GEP-NETs depending on stage and treatment steps and compare our treatment decisions to the latest treatment recommendations of European Society of Medical Oncology (ESMO) 2020 for GEP-NETs. METHODS: Patients were included in this retrospective single-center analysis from 2012-2016. All patients suffering from a GEP-NET, who were screened, treated or evaluated at ENETS Center in Zurich, Switzerland were included in analysis. Patients with any other diagnosis of NET were not included. We used Kaplan Meier estimator as well as Cox regression to compare survival rates between different sites of localization, grades or stages and treatment sequences. RESULTS: Overall, we identified 256 GEP-NETs, most in advanced stage (62%) and located in small intestine tract or pancreatic gland. Survival depended on stage, grade, primary site and duration of response for the early systemic treatment. On average patients underwent 2.6 different treatment modalities, mostly depending on stage and higher tumor grade. Surgery was performed early but also in advanced stages, usually followed by Somatostatine-Agonist modalities. In distant disease (Stage IV), we investigated a positive effect of PFS after treatment with Somatostatine Analogues (SSA) (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.21 - 0.97; p = 0.04) and systemic treatment (HR, 0.51; 95% CI, 0.26 - 0.99; p = 0.047) if patients underwent prior surgery or endoscopic resection. Kaplan Meier distributions predict shorter OS in distant disease (Stage IV), (Figure. 1; HR, 2.06; 95% CI, 1.46 - 2.89; log-rank test, p < 0.001). CONCLUSION: This retrospective analysis presents a great overview of all patients', disease and treatment characteristics of GEP-NETs at ENETS Center in Zurich, Switzerland. We illustrated survival (PFS) depending on implemented therapies. According to these findings, we formed a suggested treatment algorithm for advanced GEP-NETs, which does not differ from the latest treatment recommendation by ESMO guidelines for GEP-NETs. The results of this project may define GEP-NET patients' selection for upcoming clinical prospective studies.


Assuntos
Neoplasias Intestinais , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Estudos Retrospectivos , Estudos Prospectivos
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