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Lipid transfer proteins (LTPs) are key players in cellular homeostasis and regulation, as they coordinate the exchange of lipids between different cellular organelles. Despite their importance, our mechanistic understanding of how LTPs function at the molecular level is still in its infancy, mostly due to the large number of existing LTPs and to the low degree of conservation at the sequence and structural level. In this work, we use molecular simulations to characterize a representative dataset of lipid transport domains (LTDs) of 12 LTPs that belong to 8 distinct families. We find that despite no sequence homology nor structural conservation, the conformational landscape of LTDs displays common features, characterized by the presence of at least 2 main conformations whose populations are modulated by the presence of the bound lipid. These conformational properties correlate with their mechanistic mode of action, allowing for the interpretation and design of experimental strategies to further dissect their mechanism. Our findings indicate the existence of a conserved, fold-independent mechanism of lipid transfer across LTPs of various families and offer a general framework for understanding their functional mechanism.
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The characterization of lipid binding to lipid transfer proteins (LTPs) is fundamental to understand their molecular mechanism. However, several structures of LTPs, and notably those proposed to act as bridges between membranes, do not provide the precise location of their endogenous lipid ligands. To address this limitation, computational approaches are a powerful alternative methodology, but they are often limited by the high flexibility of lipid substrates. Here, we develop a protocol based on unbiased coarse-grain molecular dynamics simulations in which lipids placed away from the protein can spontaneously bind to LTPs. This approach accurately determines binding pockets in LTPs and provides a working hypothesis for the lipid entry pathway. We apply this approach to characterize lipid binding to bridge LTPs of the Vps13-Atg2 family, for which the lipid localization inside the protein is currently unknown. Overall, our work paves the way to determine binding pockets and entry pathways for several LTPs in an inexpensive, fast, and accurate manner.
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Proteínas de Transporte , Simulação de Dinâmica Molecular , Ligação Proteica , Sítios de Ligação , Proteínas de Transporte/metabolismo , Proteínas de Transporte/química , Proteínas de Transporte/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/química , Lipídeos/química , Proteínas Relacionadas à Autofagia/metabolismo , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/química , Proteínas de Transporte Vesicular/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/químicaRESUMO
Tobacco mosaic virus (TMV) was the first virus to be studied in detail and, for many years, TMV and other tobamoviruses, particularly tomato mosaic virus (ToMV) and tobamoviruses infecting pepper (Capsicum spp.), were serious crop pathogens. By the end of the twentieth and for the first decade of the twenty-first century, tobamoviruses were under some degree of control due to introgression of resistance genes into commercial tomato and pepper lines. However, tobamoviruses remained important models for molecular biology, biotechnology and bio-nanotechnology. Recently, tobamoviruses have again become serious crop pathogens due to the advent of tomato brown rugose fruit virus, which overcomes tomato resistance against TMV and ToMV, and the slow but apparently inexorable worldwide spread of cucumber green mottle mosaic virus, which threatens all cucurbit crops. This review discusses a range of mainly molecular biology-based approaches for protecting crops against tobamoviruses. These include cross-protection (using mild tobamovirus strains to 'immunize' plants against severe strains), expressing viral gene products in transgenic plants to inhibit the viral infection cycle, inducing RNA silencing against tobamoviruses by expressing virus-derived RNA sequences in planta or by direct application of double-stranded RNA molecules to non-engineered plants, gene editing of host susceptibility factors, and the transfer and optimization of natural resistance genes.
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Resistência à Doença , Doenças das Plantas , Plantas Geneticamente Modificadas , Tobamovirus , Tobamovirus/genética , Doenças das Plantas/virologia , Doenças das Plantas/genética , Resistência à Doença/genética , Plantas Geneticamente Modificadas/virologia , Capsicum/virologia , Capsicum/imunologia , Produtos Agrícolas/virologia , Produtos Agrícolas/genética , Solanum lycopersicum/virologia , Engenharia Genética , Vírus do Mosaico do Tabaco/genéticaRESUMO
Behavioural nudges are often criticised because they "work best in the dark". However, recent experimental evidence suggests that the effectiveness of nudges is not reduced when they are delivered transparently. Most people also endorse transparent nudges. Yet, transparent nudging may undermine human autonomy-a minority may oppose to being nudged and feel manipulated, even if they know what is happening. We propose an alternative way of maintaining autonomy that is not reducible to transparency: individuals can be asked if they consent in advance to being nudged. To assess whether consensual nudges are effective, we ask consent from 1518 UK citizens to be nudged. Subsequently, we default all participants into donating to a charity of their choice, irrespective of self-reported consent. We find that the default nudge is equally effective for both consenting and non-consenting individuals, with negligible difference in average donations. However, non-consenting individuals report higher levels of resentment and regret and lower levels of happiness and support compared to the consenting group. Based on these findings, we argue that ignoring consent can have serious ethical ramifications for policy-making with nudges.
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Consentimento Livre e Esclarecido , Humanos , Masculino , Feminino , Consentimento Livre e Esclarecido/ética , Comportamento de Escolha , Adulto , Autonomia Pessoal , Reino Unido , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Perfluoroalkyl and poly-fluoroalkyl substances (PFAS) are pervasive environmental pollutants and emerging risk factors for reproductive health. Although epidemiological evidence supports the link between these substances and male infertility, their specific effects on male fertility remain poorly understood. OBJECTIVES: Investigate the effect of perfluorooctane sulfonic acid (PFOS), the most prevalent and prominent PFAS, on bull sperm protein phosphorylation, a post-translational modification process governing sperm functionality and fertility. METHODS: We exposed bull sperm to PFOS at 10 µM (average population level) and 100 µM (high-exposure level), and analyzed global proteome and phosphoproteome profile by TMT labeling and NanoLC-MS/MS. We also measured sperm fertility functions by flow cytometry. RESULTS: PFOS at 10 µM altered sperm proteins linked to spermatogenesis and chromatin condensation, while at 100 µM, PFOS affected proteins associated with motility and fertility. We detected 299 phosphopeptides from 116 proteins, with 45 exhibiting differential expression between control and PFOS groups. PFOS dysregulated phosphorylation of key proteins (ACRBP, PRKAR2A, RAB2B, SPAG8, TUBB4B, ZPBP, and C2CD6) involved in sperm capacitation, acrosome reaction, sperm-egg interaction, and fertilization. PFOS also affected phosphorylation of other proteins (AQP7, HSBP9, IL4I1, PRKAR1A, and CCT8L2) related to sperm stress resistance and cryotolerance. Notably, 4 proteins (PRM1, ACRBP, TSSK1B, and CFAP45) exhibited differential regulation at both the proteomic and phosphoproteomic levels. Flow cytometric analysis confirmed that PFOS increased protein phosphorylation in sperm as well as reduced sperm motility, viability, calcium, and membrane potential and increased mitochondrial ROS in a dose-dependent manner. CONCLUSIONS: This study shows that PFOS exposure adversely impacts phosphorylation of proteins critical for bull sperm function and fertilization. Moreover, the concentration of PFOS influences the severity of these effects. The comprehensive bull sperm phosphoproteomics data from this study can help us understand the molecular mechanisms of environmental exposure-related male infertility.
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Strenuous exercise can result in disruption of intestinal barrier function and occurrence of gastrointestinal symptoms. The aim of this exploratory study was to elucidate systemic effects of increased intestinal permeability after high-intensity exercise. Forty-one endurance-trained subjects performed a 60-min treadmill run at 80% VO2max. Small intestinal permeability was measured as urinary excretion ratio of lactulose/rhamnose (L/R). Blood, saliva and feces were analyzed for gut barrier and immune-related biomarkers. The exercise challenge increased several markers of intestinal barrier disruption, immune function and oxidative stress. We found a negative correlation between L/R ratio and uric acid (r = -0.480), as well as a positive correlation between the L/R ratio and fecal chromogranin A in male participants (r = 0.555). No significant correlations were found between any of the markers and gastrointestinal symptoms, however, perceived exertion correlated with the combination of IL-6, IL-10 and salivary cortisol (r = 0.492). The lack of correlation between intestinal permeability and gastrointestinal symptoms could be due to minor symptoms experienced in lab settings compared to real-life competitions. The correlation between L/R ratio and uric acid might imply a barrier-protective effect of uric acid, and inflammatory processes due to strenuous exercise seem to play an important role regarding physical exhaustion.
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Biomarcadores , Exercício Físico , Humanos , Masculino , Adulto , Biomarcadores/sangue , Biomarcadores/metabolismo , Exercício Físico/fisiologia , Feminino , Mucosa Intestinal/metabolismo , Ácido Úrico/sangue , Ácido Úrico/metabolismo , Permeabilidade , Lactulose/urina , Lactulose/metabolismo , Ramnose/metabolismo , Adulto Jovem , Estresse Oxidativo , Cromogranina A/metabolismo , Hidrocortisona/sangue , Hidrocortisona/metabolismo , Saliva/metabolismoRESUMO
Countries face challenges in paying for new drugs. High prices are driven in part by exploding drug development costs, which, in turn, are driven by essential but excessive regulation. Burdensome regulation also delays drug development, and this can translate into thousands of life-years lost. We need system-wide reform that will enable less expensive, faster drug development. The speed with which COVID-19 vaccines and AIDS therapies were developed indicates this is possible if governments prioritize it. Countries also differ in how they value drugs, and generally, those willing to pay more have better, faster access. Canada is used as an example to illustrate how "incremental cost-effectiveness ratios" (ICERs) based on measures such as gains in "quality-adjusted life-years" (QALYs) may be used to determine a drug's value but are often problematic, imprecise assessments. Generally, ICER/QALY estimates inadequately consider the impact of patient crossover or long post-progression survival, therapy benefits in distinct subpopulations, positive impacts of the therapy on other healthcare or societal costs, how much governments willingly might pay for other things, etc. Furthermore, a QALY value should be higher for a lethal or uncommon disease than for a common, nonlethal disease. Compared to international comparators, Canada is particularly ineffective in initiating public funding for essential new medications. Addressing these disparities demands urgent reform.
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Antineoplásicos , Análise Custo-Benefício , Humanos , Antineoplásicos/uso terapêutico , Antineoplásicos/economia , Análise Custo-Benefício/métodos , Canadá , Anos de Vida Ajustados por Qualidade de Vida , Custos de Medicamentos , COVID-19 , Neoplasias/tratamento farmacológico , Neoplasias/economia , SARS-CoV-2RESUMO
Polyaniline (PANI) stands out as a highly promising conducting polymer with potential for advanced utilization in high-performance pseudocapacitors. Therefore, there exists a pressing need to bolster the structural durability of PANI, achievable by developing composite materials that can enhance its viability for supercapacitor applications. In this particular study, a pioneering approach was undertaken to produce a novel NiMn2O4/PANI supercapacitor electrode material. A comprehensive array of analytical techniques was employed to ascertain the structural configuration, morphology, oxidation states of elements, composition, and surface characteristics of the electrode material. The electrochemical evaluation of the NiMn2O4/PANI composite shows a specific capacitance (Cs) of 1530 ± 2 F g-1 at 1 A g-1. Significantly, the composite material displays an outstanding 93.61% retention of its capacity after an extensive 10 000 cycles, signifying remarkable cycling stability, while the 2-electrode configuration reveals a Cs value of 764 F g-1 at 5 mV s-1 and 826 F g-1 at 1 A g-1 with a smaller charge transfer resistance (Rct) value of 0.67 Ω. Chronoamperometric tests showed excellent stability of the fabricated material up to 50 h. This significant advancement bears immense promise for its potential implementation in high-efficiency energy storage systems and heralds a new phase in the development of supercapacitor technology with improved stability and performance metrics.
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Nanotechnology has transformed drug delivery, offering opportunities to enhance treatment outcomes while minimizing adverse effects. This study focuses on gelatin-coated cobalt and manganese ferrite nanoparticles for potential drug delivery applications. The synthesis involved a co-precipitation method, and the nanoparticles were characterized using various techniques, including X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), Raman spectroscopy, and vibrating sample magnetometer (VSM). Results revealed stable structures, distinct chemical features introduced by gelatin coating, and unique magnetic properties. The hemolysis assay demonstrated reduced hemolytic activity with gelatin coating, enhancing biocompatibility. Drug release studies indicated differential release profiles, with gelatin-coated cobalt ferrite exhibiting higher drug release compared to gelatin-coated manganese ferrite. The Higuchi model supported diffusion-controlled drug release for gelatin-coated cobalt ferrite. These findings suggest the potential of gelatin-coated ferrite nanoparticles for controlled and targeted drug delivery, highlighting their significance in advancing nanomedicine.
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Policymakers often face a conundrum between being transparent about policies and ensuring that those policies are effective. This challenge is particularly relevant for behavioral nudges, which are not usually disclosed. Rather than avoiding transparency, we suggest that policymakers encourage citizens to reflect on nudges to help them understand their own views and align those views with their behaviors. Using data from an online survey experiment with 24,303 respondents in G7 countries, we examine the impact of reflection on a hypothetical default nudge policy for COVID-19 booster appointments. Contrary to expectations, participants say they would be less likely to get the booster when automatically enrolled compared with a control condition. Similarly, encouraging citizens to think about the status quo (baseline) policy also reduces intentions for boosters. These interventions have no effect on approval of the policy. Further, encouraging people to think about automatic enrollment decreases approval of the policy and further decreases their intentions to get vaccinated. These findings suggest that reflection on a nudge can increase backlash from a nudge and also elicit policy disapproval, thereby aligning policy support with behavioral intentions.
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OBJECTIVES: While substantial progress has been made in engineering cartilaginous constructs for animal models, further research is needed to translate these methodologies for human applications. Evidence suggests that cultured autologous chondrocytes undergo changes in phenotype and gene expression, thereby affecting their proliferation and differentiation capacity. This study was designed to evaluate the expression of chondrogenic markers in cultured human articular chondrocytes from passages 3 (P3) and 7 (P7), beyond the current clinical recommendation of P3. METHODS: Cultured autologous chondrocytes were passaged from P3 up to P7, and quantitative polymerase chain reaction (qPCR) was used to assess mRNA expression of chondrogenic markers, including collagen type I (COLI), collagen type II (COLII), aggrecan (AGG), bone morphogenetic protein 4 (BMP4), transcription factor SOX-9 (SOX9), proteoglycan 4 (PGR4), and transformation-related protein 53 (p53), between P3 and P7. RESULTS: Except for AGG, no significant differences were found in the expression of markers between passages, suggesting the maintenance of chondrogenic potential in cultured chondrocytes. Differential expression identified between SOX9 and PGR4, as well as between COLI and SOX9, indicates that differences in chondrogenic markers are present between age groups and sexes, respectively. CONCLUSIONS: Overall, expression profiles of younger and male chondrocytes exhibit conversion of mature cartilage characteristics compared to their counterparts, with signs of dedifferentiation and loss of phenotype within-group passaging. These results may have implications in guiding the use of higher passaged chondrocytes for engineering constructs and provide a foundation for clinical recommendations surrounding the repair and treatment of articular cartilage pathology in both sexes.
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PURPOSE: This study sought to identify the sources of differential performance and misclassification error among local (Indian) and external (non-Indian) corneal specialists in identifying bacterial and fungal keratitis based on corneal photography. METHODS: This study is a secondary analysis of survey data assessing the ability of corneal specialists to identify acute bacterial versus fungal keratitis by using corneal photography. One-hundred images of 100 eyes from 100 patients with acute bacterial or fungal keratitis in South India were previously presented to an international cohort of cornea specialists for interpretation over the span of April to July 2021. Each expert provided a predicted probability that the ulcer was either bacterial or fungal. Using these data, we performed multivariable linear regression to identify factors predictive of expert performance, accounting for primary practice location and surrogate measures to infer local fungal ulcer prevalence, including locality, latitude, and dew point. In addition, Brier score decomposition was used to determine experts' reliability ("calibration") and resolution ("boldness") and were compared between local (Indian) and external (non-Indian) experts. RESULTS: Sixty-six experts from 16 countries participated. Indian practice location was the only independently significant predictor of performance in multivariable linear regression. Resolution among Indian experts was significantly better (0.08) than among non-Indian experts (0.01; P < 0.001), indicating greater confidence in their predictions. There was no significant difference in reliability between the two groups ( P = 0.40). CONCLUSION: Local cornea experts outperformed their international counterparts independent of regional variability in tropical risk factors for fungal keratitis. This may be explained by regional characteristics of infectious ulcers with which local corneal specialists are familiar.
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Úlcera da Córnea , Infecções Oculares Bacterianas , Infecções Oculares Fúngicas , Humanos , Úlcera da Córnea/diagnóstico , Úlcera da Córnea/epidemiologia , Úlcera da Córnea/complicações , Úlcera , Reprodutibilidade dos Testes , Infecções Oculares Bacterianas/diagnóstico , Infecções Oculares Bacterianas/epidemiologia , Infecções Oculares Bacterianas/etiologia , Bactérias , Infecções Oculares Fúngicas/diagnóstico , Infecções Oculares Fúngicas/epidemiologia , Infecções Oculares Fúngicas/etiologia , Índia/epidemiologiaRESUMO
Skin cancer, including the highly lethal malignant melanoma, poses a significant global health challenge with a rising incidence rate. Early detection plays a pivotal role in improving survival rates. This study aims to develop an advanced deep learning-based approach for accurate skin lesion classification, addressing challenges such as limited data availability, class imbalance, and noise. Modern deep neural network designs, such as ResNeXt101, SeResNeXt101, ResNet152V2, DenseNet201, GoogLeNet, and Xception, which are used in the study and ze optimised using the SGD technique. The dataset comprises diverse skin lesion images from the HAM10000 and ISIC datasets. Noise and artifacts are tackled using image inpainting, and data augmentation techniques enhance training sample diversity. The ensemble technique is utilized, creating both average and weighted average ensemble models. Grid search optimizes model weight distribution. The individual models exhibit varying performance, with metrics including recall, precision, F1 score, and MCC. The "Average ensemble model" achieves harmonious balance, emphasizing precision, F1 score, and recall, yielding high performance. The "Weighted ensemble model" capitalizes on individual models' strengths, showcasing heightened precision and MCC, yielding outstanding performance. The ensemble models consistently outperform individual models, with the average ensemble model attaining a macro-average ROC-AUC score of 96 % and the weighted ensemble model achieving a macro-average ROC-AUC score of 97 %. This research demonstrates the efficacy of ensemble techniques in significantly improving skin lesion classification accuracy. By harnessing the strengths of individual models and addressing their limitations, the ensemble models exhibit robust and reliable performance across various metrics. The findings underscore the potential of ensemble techniques in enhancing medical diagnostics and contributing to improved patient outcomes in skin lesion diagnosis.
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Aprendizado Profundo , Melanoma , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/diagnóstico , Melanoma/patologia , Melanoma/diagnóstico , Redes Neurais de ComputaçãoRESUMO
Solid-supported polymer membranes (SSPMs) offer great potential in material and life sciences due to their increased mechanical stability and robustness compared to solid-supported lipid membranes. However, there is still a need for expanding the functionality of SSPMs by combining them with synthetic molecular assemblies. In this study, SSPMs served as a flexible matrix for the insertion of resorcinarene monomers and their self-assembly into functional hexameric resorcinarene capsules. Resorcinarene capsules provide a large cavity with affinity specifically for cationic and polyhydroxylated molecules. While the capsules are stable in apolar organic solvents, they disassemble when placed in polar solvents, which limits their application. Here, a solvent-assisted approach was used for copolymer membrane deposition on solid support and simultaneous insertion of the resorcinarene monomers. By investigation of the molecular factors and conditions supporting the codeposition of the copolymer and resorcinarene monomers, a stable hybrid membrane was formed. The hydrophobic domain of the membrane played a crucial role by providing a sufficiently thick and apolar layer, allowing for the self-assembly of the capsules. The capsules were functional inside the membranes by encapsulating cationic guests from the aqueous environment. The amount of resorcinarene capsules in the hybrid membranes was quantified by a combination of quartz-crystal microbalance with dissipation and liquid chromatography-mass spectrometry, while the membrane topography and layer composition were analyzed by atomic force microscopy and neutron reflectometry. Functional resorcinarene capsules inside SSPMs can serve as dynamic sensors and potentially as cross-membrane transporters, thus holding great promise for the development of smart surfaces.
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OBJECTIVES: Anaemia during pregnancy is a major health challenge affecting pregnancy outcome worldwide. The objectives of this study were to investigate the impact of severe-moderate anaemia in the first trimester, as well as changes in haemoglobin during pregnancy among non-anaemic women, on foetal weight, placental blood flow and newborn anthropometrics. METHODS: In a prospective cohort study, 346 women residing in rural Tanzania were followed throughout pregnancy with serial ultrasound and newborn anthropometrics assessed within 24 h of delivery. Associations between placental blood flow, foetal weight and newborn anthropometrics with either first trimester severe-moderate anaemia (haemoglobin≤9.5 g/dL) or changes in haemoglobin from the first to the third trimester among non-anaemic women, were assessed by mixed model regression and multiple linear regression, adjusting for maternal and foetal co-variables. Foetal weights and birthweight were converted to z-scores using a population based sex-specific weight reference. RESULTS: Severe-moderate anaemia in the first trimester was associated with significantly reduced foetal weight z-scores (adjusted mean difference (aMD) -0.44 (95% CI -0.81, -0.07)) and newborn anthropometric indices (birth weight z-score aMD -0.55 (-0.9, -0.13), abdominal circumference aMD -11 mm (95% CI -20, -3)). There were no association between first trimester severe-moderate anaemia and placental blood flow. Among women who were non-anaemic in the first trimester, women with the least reduction in haemoglobin (Δ ≥ -0.3 g/dL) delivered significantly smaller newborns (birthweight z-score aMD -0.55 (-0.91, -0.20), abdominal circumference aMD -10 mm (95% CI -17, -3), compared to women with the greatest reduction (Δ haemoglobin ≤ -1.4 g/dL)). CONCLUSIONS: Severe-moderate anaemia in early pregnancy was associated with smaller newborn anthropometrics which was reflected in smaller mean foetal weights in the second and third trimester. Furthermore, among women who were non-anaemic in the first trimester, there was an association between smaller newborn anthropometrics and limited haemoglobin decrease during pregnancy, possibly reflecting insufficient plasma expansion.
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Anemia , Complicações Hematológicas na Gravidez , Gravidez , Feminino , Recém-Nascido , Humanos , Primeiro Trimestre da Gravidez , Peso Fetal , Peso ao Nascer , Estudos Prospectivos , Tanzânia/epidemiologia , Complicações Hematológicas na Gravidez/epidemiologia , Placenta , Anemia/epidemiologia , Resultado da Gravidez/epidemiologia , Hemoglobinas , Estudos de CoortesRESUMO
PURPOSE OF REVIEW: In this review, we explore the investigational applications of optical coherence tomography (OCT) in retinopathy of prematurity (ROP), the insights they have delivered thus far, and key milestones for its integration into the standard of care. RECENT FINDINGS: While OCT has been widely integrated into clinical management of common retinal diseases, its use in pediatric contexts has been undermined by limitations in ergonomics, image acquisition time, and field of view. Recently, investigational handheld OCT devices have been reported with advancements including ultra-widefield view, noncontact use, and high-speed image capture permitting real-time en face visualization. These developments are compelling for OCT as a more objective alternative with reduced neonatal stress compared to indirect ophthalmoscopy and/or fundus photography as a means of classifying and monitoring ROP. SUMMARY: OCT may become a viable modality in management of ROP. Ongoing innovation surrounding handheld devices should aim to optimize patient comfort and image resolution in the retinal periphery. Future clinical investigations may seek to objectively characterize features of peripheral stage and explore novel biomarkers of disease activity.
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Retinopatia da Prematuridade , Recém-Nascido , Humanos , Criança , Retinopatia da Prematuridade/diagnóstico , Tomografia de Coerência Óptica/métodos , Retina , Oftalmoscopia/métodos , Técnicas de Diagnóstico OftalmológicoRESUMO
Lipid trafficking is critical for the biogenesis and expansion of organelle membranes. Lipid transport proteins (LTPs) have been proposed to facilitate lipid transport at contact sites between organelles. Despite the fundamental importance of LTPs in cell physiology, our knowledge on the mechanisms of interorganelle lipid distribution remains poor due to the scarcity of assays to monitor lipid flux in vivo. In this review, we highlight the recent development of a versatile method named METALIC (Mass tagging-Enabled Tracking of Lipids in Cells), which uses a combination of enzymatic mass tagging and mass spectrometry to track lipid flux between organelles inside living cells. We discuss the methodology, its distinct advantages, limitations as well as its potential to unearth the pipelines of lipid transport and LTP function in vivo.
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Metabolismo dos Lipídeos , Humanos , Transporte Biológico , Animais , Espectrometria de Massas/métodos , Organelas/metabolismo , Lipídeos/químicaRESUMO
Under what conditions do citizens support coercive public policies? Although recent research suggests that people prefer policies that preserve freedom of choice, such as behavioural nudges, many citizens accepted stringent policy interventions like fines and mandates to promote vaccination during the COVID-19 pandemic-a pattern that may be linked to the unusually high effectiveness of COVID-19 vaccines. We conducted a large online survey experiment (N = 42,417) in the Group of Seven (G-7) countries investigating the relationship between a policy's effectiveness and public support for stringent policies. Our results indicate that public support for stringent vaccination policies increases as vaccine effectiveness increases, but at a modest scale. This relationship flattens at higher levels of vaccine effectiveness. These results suggest that intervention effectiveness can be a significant predictor of support for coercive policies but only up to some threshold of effectiveness.
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Vacinas contra COVID-19 , Vacinas , Humanos , Pandemias , Eficácia de Vacinas , Política Pública , VacinaçãoRESUMO
Although, it is well understood that sperm DNA damage is associated with infertility, the molecular details of how damaged sperm DNA affects fertility are not fully elucidated. Since sperm proteins play an important role in fertilization and post-fertilization events, the present study aimed to identify the sperm proteomic alterations in bulls with high sperm DNA Fragmentation Index (DFI%). Semen from Holstein-Friesian crossbred breeding bulls (n = 50) was subjected to Sperm Chromatin Structure Assay. Based on DFI%, bulls were classified into either high- (HDFI; n = 6), or low-DFI (LDFI; n = 6) and their spermatozoa were subjected to high throughput proteomic analysis. Liquid chromatography and mass spectrometry analysis identified 4567 proteins in bull spermatozoa. A total of 2660 proteins were found common to both the groups, while 1193 and 714 proteins were unique to HDFI and LDFI group, respectively. A total of 265 proteins were up regulated and 262 proteins were down regulated in HDFI group. It was found that proteins involved in capacitation [heparin binding (molecular function), ERK1 and ERK2 cascade (biological process), PI3K-Akt signalling (pathway), Jak-STAT signalling (pathway)], spermatogenesis [TLR signalling (pathway), gamete generation (biological process)] and DNA repair mechanism (biological process) were significantly altered in the bulls with high DFI%.
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Proteômica , Sêmen , Masculino , Bovinos , Animais , Fragmentação do DNA , Fosfatidilinositol 3-Quinases/metabolismo , Espermatozoides/metabolismo , Fertilidade , Motilidade dos EspermatozoidesRESUMO
The aphids Lipaphis erysimi pseudobrassicae (Davis) and Myzus persicae (Sulzer) pose serious threats to the production of cruciferous crops in the tropics. Understanding their population dynamics is important for developing integrated pest management programmes to minimize their damage to crops. This study investigated the effects of climatic factors, natural enemies and plant age on the population dynamics of these pests. The population density of aphids and their natural enemies in 20 cabbage plants, and weather conditions were monitored for five cropping seasons from 2019 to 2021 in two agroecological zones of Ghana (Coastal Savannah and Deciduous Forest zones). The highest population density of L. e pseudobrassicae was recorded in January (dry season) in both agroecological zones, while the highest population density for M. persicae occurred in September (minor rainy season) and August (dry spell) in the Coastal Savannah and Deciduous Forest zones, respectively. The highest aphid densities were noted to occur during periods with low relative humidity and low rainfall. The population density of L. e. pseudobrassicae was significantly negatively related to plant age, air temperature and relative humidity, and positively related to syrphids (Paragus borbonicus) and spiders in the Coastal Savannah zone, while in the Deciduous Forest zone, it was significantly positively related to coccinellids. On the other hand, M. persicae population density was significantly positively related to syrphids and coccinellids in the Deciduous Forest zone. Rainfall negatively affected syrphids in the Coastal Savannah zone, while air temperature positively affected syrphids and negatively affected spiders in the Deciduous Forest zone. Coccinellids had a significant positive relationship with relative humidity in the Deciduous Forest zone. This study provides important insights into the key factors that regulate aphid population densities on cabbage and will support development of timely interventions to manage these pests.