Biological tissues exhibit complex spatial heterogeneity that directs the functions of multicellular organisms. Quantifying protein expression is essential for elucidating processes within complex ...biological assemblies. Imaging mass spectrometry (IMS) is a powerful emerging tool for mapping the spatial distribution of metabolites and lipids across tissue surfaces, but technical challenges have limited the application of IMS to the analysis of proteomes. Methods for probing the spatial distribution of the proteome have generally relied on the use of labels and/or antibodies, which limits multiplexing and requires a priori knowledge of protein targets. Past efforts to make spatially resolved proteome measurements across tissues have had limited spatial resolution and proteome coverage and have relied on manual workflows. Here, we demonstrate an automated approach to imaging that utilizes label-free nanoproteomics to analyze tissue voxels, generating quantitative cell-type-specific images for >2000 proteins with 100-µm spatial resolution across mouse uterine tissue sections preparing for blastocyst implantation.
Seizures are the most common neurological emergency in the neonatal period and in contrast to those in infancy and childhood, are often provoked seizures with an acute cause and may be ...electrographic‐only. Hence, neonatal seizures may not fit easily into classification schemes for seizures and epilepsies primarily developed for older children and adults. A Neonatal Seizures Task Force was established by the International League Against Epilepsy (ILAE) to develop a modification of the 2017 ILAE Classification of Seizures and Epilepsies, relevant to neonates. The neonatal classification framework emphasizes the role of electroencephalography (EEG) in the diagnosis of seizures in the neonate and includes a classification of seizure types relevant to this age group. The seizure type is determined by the predominant clinical feature. Many neonatal seizures are electrographic‐only with no evident clinical features; therefore, these are included in the proposed classification. Clinical events without an EEG correlate are not included. Because seizures in the neonatal period have been shown to have a focal onset, a division into focal and generalized is unnecessary. Seizures can have a motor (automatisms, clonic, epileptic spasms, myoclonic, tonic), non‐motor (autonomic, behavior arrest), or sequential presentation. The classification allows the user to choose the level of detail when classifying seizures in this age group.
Abstract
A critical challenge during volcanic emergencies is responding to rapid changes in eruptive behaviour. Actionable advice, essential in times of rising uncertainty, demands the rapid ...synthesis and communication of multiple datasets with prognoses. The 2020–2021 eruption of La Soufrière volcano exemplifies these challenges: a series of explosions from 9–22 April 2021 was preceded by three months of effusive activity, which commenced with a remarkably low level of detected unrest. Here we show how the development of an evolving conceptual model, and the expression of uncertainties via both elicitation and scenarios associated with this model, were key to anticipating this transition. This not only required input from multiple monitoring datasets but contextualisation via state-of-the-art hazard assessments, and evidence-based knowledge of critical decision-making timescales and community needs. In addition, we share strategies employed as a consequence of constraints on recognising and responding to eruptive transitions in a resource-constrained setting, which may guide similarly challenged volcano observatories worldwide.
Mass-spectrometry-based proteomic analysis is a powerful approach for discovering new disease biomarkers. However, certain critical steps of study design such as cohort selection, evaluation of ...statistical power, sample blinding and randomization, and sample/data quality control are often neglected or underappreciated during experimental design and execution. This tutorial discusses important steps for designing and implementing a liquid-chromatography-mass-spectrometry-based biomarker discovery study. We describe the rationale, considerations and possible failures in each step of such studies, including experimental design, sample collection and processing, and data collection. We also provide guidance for major steps of data processing and final statistical analysis for meaningful biological interpretations along with highlights of several successful biomarker studies. The provided guidelines from study design to implementation to data interpretation serve as a reference for improving rigor and reproducibility of biomarker development studies.
The emergence of viral epidemics throughout the world is of concern due to the scarcity of available effective antiviral therapeutics. The discovery of new antiviral therapies is imperative to ...address this challenge, and antiviral peptides (AVPs) represent a valuable resource for the development of novel therapies to combat viral infection. We present a new machine learning model to distinguish AVPs from non-AVPs using the most informative features derived from the physicochemical and structural properties of their amino acid sequences. To focus on those features that are most likely to contribute to antiviral performance, we filter potential features based on their importance for classification. These feature selection analyses suggest that secondary structure is the most important peptide sequence feature for predicting AVPs. Our Feature-Informed Reduced Machine Learning for Antiviral Peptide Prediction (FIRM-AVP) approach achieves a higher accuracy than either the model with all features or current state-of-the-art single classifiers. Understanding the features that are associated with AVP activity is a core need to identify and design new AVPs in novel systems. The FIRM-AVP code and standalone software package are available at https://github.com/pmartR/FIRM-AVP with an accompanying web application at https://msc-viz.emsl.pnnl.gov/AVPR .
Convergent evolution dictates that diverse groups of viruses will target both similar and distinct host pathways to manipulate the immune response and improve infection. In this study, we sought to ...leverage this uneven viral antagonism to identify critical host factors that govern disease outcome. Utilizing a systems-based approach, we examined differential regulation of IFN-γ–dependent genes following infection with robust respiratory viruses including influenza viruses A/influenza/Vietnam/1203/2004 (H5N1-VN1203) and A/influenza/California/04/2009 (H1N1-CA04) and coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV). Categorizing by function, we observed down-regulation of gene expression associated with antigen presentation following both H5N1-VN1203 and MERS-CoV infection. Further examination revealed global down-regulation of antigen-presentation gene expression, which was confirmed by proteomics for both H5N1-VN1203 and MERS-CoV infection. Importantly, epigenetic analysis suggested that DNA methylation, rather than histone modification, plays a crucial role in MERS-CoV–mediated antagonism of antigen presentation gene expression; in contrast, H5N1-VN1203 likely utilizes a combination of epigenetic mechanisms to target antigen presentation. Together, the results indicate a common mechanism utilized by H5N1-VN1203 and MERS-CoV to modulate antigen presentation and the host adaptive immune response.
Type 1 diabetes is an autoimmune disease in which one's own immune system destroys insulin‐secreting beta cells in the pancreas. This process results in life‐long dependence on exogenous insulin for ...survival. Both genetic and environmental factors play a role in disease initiation, progression, and ultimate clinical diagnosis of type 1 diabetes. This review will provide background on the natural history of type 1 diabetes and the role of genetic factors involved in the complement system, as several recent studies have identified changes in levels of these proteins as the disease evolves from pre‐clinical through to clinically apparent disease.
Background
Adverse birth outcomes (ABOs) are considered the most common factor of deaths in early childhood. Inequalities in child mortality occur due to interactions between intrinsic and ...socio-environmental factors related to socioeconomic disadvantage. There are, however, few studies investigating the impact of ABOs on mortality in terms of parental SEP.
Methods
Using the Under-5 Infant Birth-Death Cohort Data in Korea, a pooled retrospective birth cohort of all children born in 2012-2014 was built (N = 1,356,584). We analyzed neonatal, post-neonatal, and childhood mortality by ABOs and with the interaction of parental SEP using the Cox proportional hazard regression model for survival analyses. We further stratified the analysis both by parental SEP and child age. Multiple logistic regression was performed to confirm the social inequalities in ABO itself.
Results
After adjusting for covariates, children born with ABOs presented higher risk of mortality for all periods. For post-neonatal period, lower maternal education showed significant interaction effect with LBW (HR = 0.57; 95% CI = 0.39-0.85), PTB (HR = 0.53; 95% CI = 0.33-0.86), LBW & PTB (HR = 0.67; 95% CI = 0.54-0.83) while lower paternal education (HR = 0.67; 95% CI = 0.54-0.82) and maternal unemployment (HR = 0.80; 95% CI = 0.63-0.99) showed significance for babies with LBW & PTB. However, stratification analyses suggested that the impact of ABOs on mortality was greater for children born to lower parental SEP in neonatal period. Meanwhile apparent social inequalities in ABOs were suggested from regression analyses.
Conclusions
We confirmed social inequalities in the incidence of ABOs as well as mortalities from ABOs. However, the difference in mortality between babies with and without ABOs was greater for advantaged children. Policies to reduce the mortality of children with ABOs as well as those of healthy children among socioeconomically disadvantaged families are required.
Key messages
* Social inequalities in mortality from ABOs were apparent especially in the neonatal period while the incidence of ABOs itself was greater among children from disadvantaged families.
* Disadvantaged children are more likely to die not only from ABOs but also from other socio-environmental determinants, especially in the post-neonatal period than their counterparts.
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