Deep Proteome Profiling Enabled Functional Annotation and Data-Independent Quantification of Proline Hydroxylation Targets

Proline hydroxylation (Hyp) regulates protein structure, stability and protein-protein interaction and is widely involved in diverse metabolic and physiological pathways in cells and diseases. To reveal functional features of the proline hydroxylation proteome, we integrated various data sources for deep proteome profiling of proline hydroxylation proteome in human and developed HypDB (https://www.HypDB.site), an annotated database and web server for proline hydroxylation proteome. HypDB provides site-specific evidence of modification based on extensive LC-MS analysis and literature mining with 15319 non-redundant Hyp sites and 8226 sites with high confidence on human proteins. Annotation analysis revealed significant enrichment of proline hydroxylation on key functional domains and tissue-specific distribution of Hyp abundance across 26 types of human organs and fluids and 6 cell lines. The network connectivity analysis further revealed a critical role of proline hydroxylation in mediating protein-protein interactions. Moreover, the spectral library generated by HypDB enabled data-independent analysis (DIA) of clinical tissues and the identification of novel Hyp biomarkers in lung cancer and kidney cancer. Taken together, our integrated analysis of human proteome with publicly accessible HypDB revealed functional diversity of Hyp substrates and provides a quantitative data source to characterize proline hydroxylation in pathways and diseases.

Sex-specific distribution and classification of Wolbachia infections and mitochondrial DNA haplogroups in Aedes albopictus from the Indo-Pacific

The arbovirus vector Aedes albopictus (Asian tiger mosquito) is common throughout the Indo-Pacific region, where most global dengue transmission occurs. We analysed population genomic data and tested for cryptic species in 160 Ae. albopictus sampled from 16 locations across this region. We found no evidence of cryptic Ae. albopictus but found multiple intraspecific COI haplotypes partitioned into groups representing three Asian lineages: East Asia, Southeast Asia and Indonesia. Papua New Guinea (PNG), Vanuatu and Christmas Island shared recent coancestry, and Indonesia and Timor-Leste were likely invaded from East Asia. We used a machine learning trained on morphologically sexed samples to classify sexes using multiple genetic features and then characterized the w AlbA and w AlbB Wolbachia infections in 664 other samples. The w AlbA and w AlbB infections as detected by qPCR showed markedly different patterns in the sexes. For females, most populations had a very high double infection incidence, with 67% being the lowest value (from Timor-Leste). For males, the incidence of double infections ranged from 100% (PNG) to 0% (Vanuatu). Only 6 females were infected solely by the w AlbA infection, while rare uninfected mosquitoes were found in both sexes. The w AlbA and w AlbB densities varied significantly among populations. For mosquitoes from Torres Strait and Vietnam, the w AlbB density was similar in single-infected and superinfected ( w AlbA and w AlbB) mosquitoes. There was a positive association between w AlbA and w AlbB infection densities in superinfected Ae. albopictus . Our findings provide no evidence of cryptic species of Ae. albopictus in the region and suggest site-specific factors influencing the incidence of Wolbachia infections and their densities. We also demonstrate the usefulness of SNPs as sex-specific mosquito markers. The results provide baseline data for the exploitation of Wolbachia -induced cytoplasmic incompatibility (CI) in dengue control.

COVID-19 surveillance in the Flemish school system: development of systematic data collection within the Public Health School System and descriptive analysis of cases reported between October 2020 and June 2021

Background The age specific distribution of SARS-CoV-2 cases in schools is not well described. The numbers recorded reflect the intensity of community transmission while being shaped by biases from age-dependent testing regimes and effective age-specific interventions. A case-surveillance system was introduced within the Flemish school and health-prevention network during the 2020-2021 school year. We present epidemiological data of in-school reported cases in pre-, primary and secondary schools based on the surveillance system, in conjunction with test data and community cases from October 2020 to June 2021. Methods We describe the development of the surveillance system and provide the number of reported cases and standardized rates per grade over time. We calculate absolute and relative differences between incidence cases by grade of primary (grades 1-6) and secondary-school (grades 7-12) and compare these to grades 7-8, relating them to non-pharmaceutical infection prevention interventions. Cumulative population incidences (IP) stratified by age, province and social-economic status (SES) of the school population are presented with their 95% confidence intervals (CI). Results A total of 59,996 COVID-19 cases were reported in the school surveillance system, with the highest population adjusted IP in grade 11-12 of 7.39% (95%CI 7.24-7.53) and ranging from 2.23–6.25% from pre-school through grade 10. Age-specific reduction in in-person teaching and introduction of masks, are temporally associated with decreases in incident cases by grades. Lower pupil SES is associated with increased cumulative cases (excess 2,739/100,000 pupils compared to highest SES tertile). Community testing volumes varied more for children compared to adults, with overall higher child test-positivity. Holidays influence capturing of cases by the system, however efficiency increased to above 75% after further automation and integration in existing structures. Conclusion Integration of case surveillance within an electronic school health system is feasible, provides data to follow up the epidemic evolution in schoolchildren and should be part of public health surveillance and pandemic preparedness. The relationship towards community transmission needs careful evaluation because of age-different testing regimens. In the Flemish region, case incidence within schools follows an age gradient that is mitigated through grade specific interventions, while differences by SES remain.

‘Fact type’ complementizer in Guadeloupean Creole

This paper aims to give account of the distribution in Guadeloupean Creole of the form of the complementizer kè. It claims that it has a specific distribution, as it seems to appear in opposition to the zero form. Besides a sociolinguistic component, the presence of kè is associable with the fact type semantics of the completive event (Dixon 2006), and so do other grammatical functions and markers that are featured in the completive clauses when kè is present, such as independent TAM markers on the verb and the obligatory featuring of a subject form in case of subject coreference.

Neural Network Based Filtering Method for Cancer Detection

Objective: The growth of anomalous cells in the human body in an uncontrolled manner is characterized as cancer. The detection of cancer is a multi-stage process in the clinical examination. Methods: It is mainly involved with the assistance of radiological imaging. The imaging technique is used to identify the spread of cancer in the human body. This imaging-based detection can be improved by incorporating the Image Processing methodologies. In image processing, the preprocessing is applied at the lower-level abstraction. It removes the unwanted noise pixel present in the image, which also distributes the pixel values based on the specific distribution method. Results: Neural Network is a learning and processing engine, which is mainly used to create cognitive intelligence in various domains. In this work, the Neural Network (NN) based filtering approach is developed to improve the preprocessing operation in the cancer detection process. Conclusion: The performance of the proposed filtering method is compared with the existing linear and non-linear filters in terms of Mean Squared Error (MSE), Peak Signal to Noise Ratio (PSNR) and Image Enhancement Factor (IEF).

Local Assessment of the Immunohistochemical Expression of Foxp3 + Regulatory T Lymphocytes in the Different Pathological Forms Associated with Bovine Paratuberculosis

Background Mycobacterium avium subsp. paratuberculosis infected animals show a variety of granulomatous lesions: from focal forms, restricted to the gut-associated lymphoid tissue (GALT), related to latency and resistance, to diffuse lesions, with abundant (multibacillary) or scant (paucibacillary) bacteria, seen in clinical stages. Factors that determine the response to the infection and responsible for the occurrence of the different types of lesion are still not fully determined. It has been seen that regulatory T cells (Treg) play an important role in the progress of various diseases where they act on the limitation of the immunopathology associated with the immune response. In the case of paratuberculosis (PTB) the role of Treg lymphocytes in the immunity against Map is far away to be completely understood; therefore, several studies addressing this subject have appeared recently. The aim of this work was to assess, by immunohistochemical methods, the presence of Foxp3+ T lymphocytes in intestinal samples with different types of lesions seen in cows with PTB. Methods Intestinal samples of twenty cows showing the different pathological forms of PTB were evaluated: uninfected controls (n = 5), focal lesions (n = 5), diffuse paucibacillary (n = 5) and diffuse multibacillary (n = 5) forms. Foxp3+ lymphocyte distribution was assessed by differential cell count in intestinal lamina propria (LP), gut-associated lymphoid tissue (GALT) and mesenteric lymph node (MLN). Results A significant increase in the number of Foxp3+ T cells was observed in all infected animals, but this increase was only significant in cows with focal lesions and, to a lesser extent, in animals with diffuse paucibacillary forms. The former showed the highest numbers, significantly different from those found in cows with diffuse lesions, where no differences were noted between the two forms. No specific distribution pattern was observed within the granulomatous lesions in any of the groups. Conclusions The increase of Foxp3+ T cells in focal forms, that have been associated with latency or resistance to infection, suggest an anti-inflammatory action of these cells at these stages, helping to prevent exacerbation of the inflammatory response, as occurs in diffuse forms, responsible for the appearance of clinical signs.

Region-specific distribution of transversal-axial tubule system organization underlies heterogeneity of calcium dynamics in the right atrium

The atrial myocardium demonstrates the highly heterogeneous organization of the transversal-axial tubule system (TATS), while its anatomical distribution and region-specific impact on Ca2+ dynamics remain unknown. We developed a novel method for high-resolution confocal imaging of TATS in intact live mouse atrial myocardium and applied a Matlab-based computational algorithm for the automated analysis of TATS integrity. We observed a 2-fold higher (P<0.01) TATS density in the right atrial appendage (RAA) than in the inter-caval region (ICR, the anatomical region between the superior vena cava and atrioventricular junction and between the crista terminalis and inter-atrial septum). While RAA predominantly consisted of well-tubulated myocytes, ICR showed partially tubulated/untubulated cells. Similar TATS distribution was also observed in healthy human atrial myocardium sections. In both mouse atrial preparations and isolated mouse atrial myocytes, we observed a strong anatomical correlation between TATS distribution and Ca2+ transient synchronization and rise-up time. This region-specific difference in Ca2+ transient morphology disappeared after formamide-induced detubulation. ICR myocytes showed a prolonged action potential duration at 80% of repolarization as well as a significantly lower expression of RyR2 and Cav1.2 proteins, but similar levels of NCX1 and Cav1.3 compared to RAA tissue. Our findings provide a detailed characterization of the region-specific distribution of TATS in mouse and human atrial myocardium highlighting the structural foundation for anatomical heterogeneity of Ca2+ dynamics and contractility in the atria. These results could indicate different roles of TATS in Ca2+ signaling at distinct anatomical regions of the atria and provide mechanistic insight into pathological atrial remodeling.

Transposable Elements in the Genome of the Lichen-Forming Fungus Umbilicaria pustulata and Their Distribution in Different Climate Zones along Elevation

Transposable elements (TEs) are an important source of genome plasticity across the tree of life. Drift and natural selection are important forces shaping TE distribution and accumulation. Fungi, with their multifaceted phenotypic diversity and relatively small genome size, are ideal models to study the role of TEs in genome evolution and their impact on the host’s ecological and life history traits. Here we present an account of all TEs found in a high-quality reference genome of the lichen-forming fungus Umbilicaria pustulata, a macrolichen species comprising two climatic ecotypes: Mediterranean and cold temperate. We trace the occurrence of the newly identified TEs in populations along three elevation gradients using a Pool-Seq approach to identify TE insertions of potential adaptive significance. We found that TEs cover 21.26% of the 32.9 Mbp genome, with LTR Gypsy and Copia clades being the most common TEs. We identified 28 insertions displaying consistent insertion frequency differences between the two host ecotypes across the elevation gradients. Most of the highly differentiated insertions were located near genes, indicating a putative function. This pioneering study of the content and climate niche-specific distribution of TEs in a lichen-forming fungus contributes to understanding the roles of TEs in fungal evolution.

Probability Density Functions for Prediction Using Normal and Exponential Distribution

When data are found to be realizations of a specific distribution, constructing the probability density function based on this distribution may not lead to the best prediction result. In this study, numerical simulations are conducted using data that follow a normal distribution, and we examine whether probability density functions that have shapes different from that of the normal distribution can yield larger log-likelihoods than the normal distribution in the light of future data. The results indicate that fitting realizations of the normal distribution to a different probability density function produces better results from the perspective of predictive ability. Similarly, a set of simulations using the exponential distribution shows that better predictions are obtained when the corresponding realizations are fitted to a probability density function that is slightly different from the exponential distribution. These observations demonstrate that when the form of the probability density function that generates the data is known, the use of another form of the probability density function may achieve more desirable results from the standpoint of prediction.