Resolving Missing Protein Problems Using Functional Class Scoring

Despite technological advances in proteomics, incomplete coverage and inconsistency issues persist, resulting in “data holes”. These data holes cause the missing protein problem (MPP), where relevant proteins are persistently unobserved, or sporadically observed across samples. This hinders biomarker and drug discovery from proteomics data. Network-based approaches are powerful: The Functional Class Scoring (FCS) method using protein complexes was able to easily recover missed proteins with weak or partial support. However, there are limitations: The verification approach (in determining missing protein recovery) is potentially biased as the test data was based on relatively outdated Data-Dependent Acquisition (DDA) proteomics and FCS does not provide a scoring scheme for individual protein components (in significant complexes). To address these issues: First, we devised a more rigorous evaluation of FCS based on same-sample technical replicates. And second, we evaluate using data from more recent Data-Independent Acquisition (DIA) technologies (viz. SWATH).Although cross-replicate examination reveals some inconsistencies amongst same-class samples, tissue-differentiating signal is nonetheless strongly conserved. This confirms FCS as a viable method that selects biologically meaningful networks. We also report that predicted missing proteins are statistically significant based on FCS p-values. Although cross-replicate verification rates are not spectacular, the predicted missing proteins as a whole, have higher peptide support than non-predicted proteins. FCS also has the capacity to predict missing proteins that are often lost due to weak specific peptide support. As a yet unresolved limitation, we find that FCS cannot assign meaningful probabilities to individual protein components (no relationship between actual probability of verification and FCS-assigned probability) as it only provides a p-value at the level of complexes.

Assessing the awareness of young people in Yakutsk of the municipal youth policy implementation

В «Основах государственной молодежной политики Российской Федерации на период до 2025 года» стратегическим приоритетом названо создание условий для формирования личности гармоничной, постоянно совершенствующейся, эрудированной, конкурентоспособной, неравнодушной, обладающей прочным нравственным стержнем, способной при этом адаптироваться к меняющимся условиям и восприимчивой к новым созидательным идеям. Молодёжную политику в городе Якутске реализует Управлением общественных связей и молодежной политики, которое является отраслевым (функциональным) органом местной администрации, входящим в структуру Окружной администрации города Якутска. Управление обеспечивает осуществление полномочий в сфере молодежной и семейной политики на территории города. Ежегодно Управление проводит множество мероприятий в рамках реализации программ муниципальной молодежной политики: акций помощи, деловых и развлекательных игр, молодёжных форумов и т.д. Одной из слабых сторон молодежной политики является неполный охват целевой аудитории, отсутствие координации между отдельными участниками молодежной политики, неосведомленность молодежи о молодежной политике в целом и мероприятиях, проводимых в рамках осуществления программ молодежной политики. В статье представлены результаты исследования информированности молодёжи г. Якутска о муниципальной молодежной политике в целом и о деятельности Управления общественных связей и молодежной политики. Исследование проводилось путем простого анкетирования, проводимого в электронной форме посредством Google-анкет. Кроме анализа ответов, в ходе исследования были изучены различные информационные источники на предмет полноты освещения реализуемой молодежной политики. На основе полученных данных были сделаны выводы о недостаточной информированности молодежи и предложены некоторые мероприятия, которые могут способствовать как получению информации, так и оценке реализации молодежной политики, установлению обратной связи. In the “Fundamentals of the State Youth Policy of the Russian Federation for the Period up to 2025”, the strategic priority is the creation of conditions for the formation of a harmonious personality, constantly improving, erudite, competitive, not indifferent, possessing a strong moral core, capable of adapting to changing conditions and receptive to new creative ideas. The youth policy in the city of Yakutsk is implemented by the Department of Public Relations and Youth Policy, which is a sectoral (functional) body of the local administration, which is a part of the structure of the District Administration of the city of Yakutsk. The Department ensures the exercise of powers in the field of youth and family policy in the city. Every year, the Department holds many events within the framework of implementing the municipal youth policy programs: charity actions, business and entertainment games, youth forums, etc. One of the weaknesses of the youth policy is incomplete coverage of the target audience, lack of coordination between individual staekholders, lack of awareness of the youth of the youth policy in general and activities carried out within the framework of the youth policy programs. The article presents the results of a survey of the awareness of young people in Yakutsk of the municipal youth policy in general and about the activities of the Department of Public Relations and Youth Policy. The research was done by means of a simple questionnaire, carried out in electronic form using Google-questionnaires. In addition to analyzing the answers, in the course of the study, various information sources were studied for the completeness of coverage of the implemented youth policy. Based on the data obtained, conclusions were drawn about the lack of awareness of young people and some measures were proposed that could contribute to both obtaining information and assessing the implementation of youth policy, establishing feedback.

Electrodeposition of Cu-Ag Alloy Films at n-Si(001) and Polycrystalline Ru Substrates

Electrodeposition of Cu-Ag films from acidic sulfate bath was conducted at n-Si(001) and polycrystalline Ru substrates. Significant nucleation overpotential of 0.4 V is observed with the Cu-Ag bath at n-Si(001) substrate, whereas the electrodeposition of Cu-Ag at Ru substrate is influenced by Ru oxides at the surface. Incomplete coverage of Si substrate by Cu-Ag deposit was observed from the deposition systems without Ag(I), or with 0.1 mM Ag(I), comparing with the compact Cu-Ag film obtained with the deposition bath containing 0.01 mM Ag(I). Layered and faceted Cu-Ag deposit was observed at small Cu deposition overpotential with the Ru substrate. Phase composition of the Cu-Ag deposits at n-Si(001) substrate from electrolyte with various Ag(I) concentrations is examined by XRD. Limited solubility of Ag (0.4 at.%) was observed in fcc-Cu until phase separation occurs. The classical model for nucleation kinetics in electrodeposition was used to examine the potentiostatic transients of the Cu-Ag electrodeposition at n-Si(001) substrate.

Role of the facial artery musculomucosal flap in the reconstruction of palatal defects

The facial artery musculomucosal flap (FAMM flap) is a convenient option for covering complicated palatal defects, as it is a local flap inside the oral cavity with good tissue quality and minimal drawbacks. The present prospective study included 17 patients, 7 males and 10 females. Most of the patients had palatal fistulae, after cleft palate surgical repair; only one had a post-traumatic palatal defect. Superiorly based FAMM flaps were used for eight patients, and inferiorly based FAMM flaps were used for nine patients. A speech specialist assessed all patients, postoperatively. The range of follow-up time was from two to four years. In the majority of cases, reconstruction was successful and uneventful. Patients were satisfied regarding oral function. Complications were minor, which include incomplete coverage, bulkiness, temporary hardness and dimpling. The FAMM flap is a very useful, versatile, and technically easy flap for covering difficult palatal defects.

Low-field 1H NMR relaxometry of water molecules confined in microporous UiO-66

Water molecules confined in a microporous metal–organic framework (MOF) UiO-66 are characterized by a low-field 1H nuclear magnetic resonance (NMR) spectroscopy. Measurements are performed of the longitudinal ([Formula: see text] and transverse ([Formula: see text] relaxation times as a function of water content from fully saturated to incomplete coverage of the first-adsorbed monolayer. The results obtained indicate that the relaxation of water molecules confined in UiO-66 is within the fast-exchange regime. When the amount of water exceeds filling ratio [Formula: see text] = 0.4, the averaged relaxation time is approximately linearly dependent on water filling ratio in pore. When the water amount cannot support a full coverage of surface monolayer, the relaxation rate increases with less filling ratio, illustrating that the mobility of water molecules is more restricted. Analysis of the measured values and the simulated ones leads to the conclusion that the surface-affected zone in UiO-66 is not confined to the surface monolayer.

A Case of In Situ Phage Therapy against Staphylococcus aureus in a Bone Allograft Polymicrobial Biofilm Infection: Outcomes and Phage-Antibiotic Interactions

Phage therapy (PT) shows promising potential in managing biofilm infections, which include refractory orthopedic infections. We report the case of a 13-year-old girl who developed chronic polymicrobial biofilm infection of a pelvic bone allograft after Ewing’s sarcoma resection surgery. Chronic infection by Clostridium hathewayi, Proteus mirabilis and Finegoldia magna was worsened by methicillin-susceptible Staphylococcus aureus exhibiting an inducible Macrolides-Lincosamides-Streptogramin B resistance phenotype (iMLSB). After failure of conventional conservative treatment, combination of in situ anti-S. aureus PT with surgical debridement and intravenous antibiotic therapy led to marked clinical and microbiological improvement, yet failed to prevent a recurrence of infection on the midterm. This eventually led to surgical graft replacement. Multiple factors can explain this midterm failure, among which incomplete coverage of the polymicrobial infection by PT. Indeed, no phage therapy against C. hathewayi, P. mirabilis or F. magna could be administered. Phage-antibiotic interactions were investigated using OmniLog® technology. Our results suggest that phage-antibiotic interactions should not be considered “unconditionally synergistic”, and should be assessed on a case-by-case basis. Specific pharmacodynamics of phages and antibiotics might explain these differences. More than two years after final graft replacement, the patient remains cured of her sarcoma and no further infections occurred.

CoVizu: Rapid analysis and visualization of the global diversity of SARS-CoV-2 genomes

Phylogenetics has played a pivotal role in the genomic epidemiology of SARS-CoV-2, such as tracking the emergence and global spread of variants, and scientific communication. However, the rapid accumulation of genomic data from around the world - with over two million genomes currently available in the GISAID database - is testing the limits of standard phylogenetic methods. Here, we describe a new approach to rapidly analyze and visualize large numbers of SARS-CoV-2 genomes. Using Python, genomes are filtered for problematic sites, incomplete coverage, and excessive divergence from a strict molecular clock. All differences from the reference genome, including indels, are extracted using minimap2, and compactly stored as a set of features for each genome. For each Pango lineage (https://cov-lineages.org), we collapse genomes with identical features into 'variants', generate 100 bootstrap samples of the feature set union to generate weights, and compute the symmetric differences between the weighted feature sets for every pair of variants. The resulting distance matrices are used to generate neigihbor-joining trees in RapidNJ and converted into a majority-rule consensus tree for the lineage. Branches with support values below 50% or mean lengths below 0.5 differences are collapsed, and tip labels on affected branches are mapped to internal nodes as directly-sampled ancestral variants. Currently, we process about 1.6 million genomes in approximately nine hours on 34 cores. The resulting trees are visualized using the JavaScript framework D3.js as 'beadplots', in which variants are represented by horizontal line segments, annotated with beads representing samples by collection date. Variants are linked by vertical edges to represent branches in the consensus tree. These visualizations are published at https://filogeneti.ca/CoVizu. All source code was released under an MIT license at https://github.com/PoonLab/covizu.

Zic1 advances epaxial myotome morphogenesis to cover the neural tube via Wnt11r

The dorsal axial muscles, or epaxial muscles, are a fundamental structure covering the spinal cord and vertebrae, as well as mobilizing the vertebrate trunk. To date, mechanisms underlying the morphogenetic process shaping the epaxial myotome are largely unknown. To address this, we used the medaka zic1/zic4-enhancer mutant Double anal fin (Da), which exhibits ventralized dorsal trunk structures resulting in impaired epaxial myotome morphology and incomplete coverage over the neural tube. In wild type, dorsal dermomyotome (DM) cells, progenitors of myotomal cells, reduce their proliferative activity after somitogenesis and subsequently form unique large protrusions extending dorsally, potentially guiding the epaxial myotome dorsally. In Da, by contrast, DM cells maintain the high proliferative activity and form mainly small protrusions. By combining RNA- and ChIP-sequencing analyses, we revealed direct targets of Zic1 which are specifically expressed in dorsal somites and involved in various aspects of development, such as cell migration, extracellular matrix organization and cell-cell communication. Among these, we identified wnt11r as a crucial factor regulating both cell proliferation and protrusive activity of DM cells. We propose that the dorsal movement of the epaxial myotome is guided by DM cells and that Zic1 empowers this activity via Wnt11r to achieve the neural tube coverage.

Montenegro

This chapter examines health politics and the health system in Montenegro based on compulsory social health insurance. It traces the post-communist development of the Montenegrin healthcare system that started with incremental privatization and continued toward a more decisive move toward liberalization through the 2004 reforms, which included, among other elements, a stronger role of private healthcare delivery and the introduction of different types of voluntary insurance. As the chapter notes, the main issues facing the health system in Montenegro are incomplete coverage, limited access to healthcare, and lack of regulation of private healthcare provision.