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The pervasive availability of publicly available microbial genomes has opened many new avenues for microbiology research, yet it also demands robust quality control and consistent annotation pipelines to ensure meaningful biological insights. proGenomes4 (prokaryotic Genomes v4) addresses this challenge by providing a resource of nearly 2 million high-quality microbial genomes, a doubling in scale from previous versions, encompassing over 7 billion genes. Each genome underwent rigorous quality assessment and comprehensive functional annotation by applying multiple standardized annotation workflows, including the systematic identification of mobile genetic elements and biosynthetic gene clusters. proGenomes4 contains 32 887 species with ecological habitat metadata as well as precomputed pan-genomes. This substantially expanded resource provides the microbiology community with a foundation for large-scale comparative studies and is freely accessible via a newly developed command line interface and at https://progenomes.embl.de/.
Microbes differ greatly in their organismal structure, physiology, and environmental adaptation, yet information about these phenotypic traits is dispersed across multiple databases and is largely unavailable for taxa that remain uncultured. Here, we present metaTraits, a unified and accessible trait resource that integrates culture-derived trait information from BacDive, BV-BRC, JGI IMG, and GOLD with genome-based predictions for medium and high-quality isolate and metagenome-assembled genomes (MAGs) from proGenomes and SPIRE. metaTraits covers over 2.2 million genomes and >140 harmonized traits mapped to standardized ontologies, spanning cell morphology (e.g. shape, size, and Gram staining), physiology (e.g. motility and sporulation), metabolic and enzymatic activities, environmental preferences (e.g. temperature, salinity, and oxygen tolerance), and lifestyle categories. All records are linked to the original evidence, and species are cross-linked to NCBI and GTDB taxonomies. The interactive metaTraits website provides search and visualization tools, taxonomy-level summaries, and two workflows for annotating user-submitted genomes or community profiles. metaTraits substantially advances accessibility and interoperability of microbial trait data, enabling comprehensive trait-based analyses of microbiomes across diverse environments. metaTraits is accessible via https://metatraits.embl.de.
Microbes are ubiquitous on Earth, forming microbiomes that sustain macroscopic life and biogeochemical cycles. Microbial dispersal, driven by natural processes and human activities, interconnects microbiomes across habitats, yet most comparative studies focus on specific ecosystems. To study planetary microbiome structure, function, and inter-habitat interactions, we systematically integrated 85,604 public metagenomes spanning diverse habitats worldwide. Using species-based unsupervised clustering and parameter modeling, we delineated 40 habitat clusters and quantified their ecological similarity. Our framework identified key drivers shaping microbiome structure, such as ocean temperature and host lifestyle. Regardless of biogeography, microbiomes were structured primarily by host-associated or environmental conditions, also reflected in genomic and functional traits inferred from 2,065,975 genomes. Generalists emerged as vehicles thriving and facilitating gene flow across ecologically disparate habitat types, illustrated by generalist-mediated horizontal transfer of an antibiotic resistance island across human gut and wastewater, further dispersing to environmental habitats, exemplifying human impact on the planetary microbiome.
Staphylococcus epidermidis, a commensal bacterium inhabiting collagen-rich areas like human skin, has gained significance due to its probiotic potential in the nasal microbiome and as a leading cause of nosocomial infections. While infrequently leading to severe illnesses, S. epidermidis exerts a significant influence, particularly in its close association with implant-related infections and its role as a classic opportunistic biofilm former. Understanding its opportunistic nature is crucial for developing novel therapeutic strategies, addressing both its beneficial and pathogenic aspects, and alleviating the burdens it imposes on patients and healthcare systems. Here, we employ genome-scale metabolic modeling as a powerful tool to elucidate the metabolic capabilities of S. epidermidis. We created a comprehensive computational resource for understanding the organism's growth conditions within diverse habitats by reconstructing and analyzing a manually curated and experimentally validated metabolic model. The final network, iSep23, incorporates 1,415 reactions, 1,051 metabolites, and 705 genes, adhering to established community standards and modeling guidelines. Benchmarking with the Metabolic Model Testing suite yields a high score, indicating the model's remarkable semantic quality. Following the findable, accessible, interoperable, and reusable (FAIR) data principles, iSep23 becomes a valuable and publicly accessible asset for subsequent studies. Growth simulations and carbon source utilization predictions align with experimental results, showcasing the model's predictive power. Ultimately, this work provides a robust foundation for future research aimed at both exploiting the probiotic potential and mitigating the pathogenic risks posed by S. epidermidis. Staphylococcus epidermidis, a bacterium commonly found on human skin, has shown probiotic effects in the nasal microbiome and is a notable causative agent of hospital-acquired infections. While these infections are typically non-life-threatening, their economic impact is considerable, with annual costs reaching billions of dollars in the United States. To better understand its opportunistic nature, we employed genome-scale metabolic modeling to construct a detailed network of S. epidermidis's metabolic capabilities. This model, comprising over a thousand reactions, metabolites, and genes, adheres to established standards and demonstrates solid benchmarking performance. Following the findable, accessible, interoperable, and reusable (FAIR) data principles, the model provides a valuable resource for future research. Growth simulations and predictions closely match experimental data, underscoring the model's predictive accuracy. Overall, this work lays a solid foundation for future studies aimed at leveraging the beneficial properties of S. epidermidis while mitigating its pathogenic potential.
Since the rise of cellular life, transmembrane proteins (TMPs) have been crucial to various cellular processes through their central role as gates and gatekeepers. Despite their importance, experimental high-resolution structures for TMPs remain underrepresented due to experimental challenges. Given its performance leap, structure predictions have begun to close the gap. However, identifying the membrane regions and topology in three-dimensional structure files on a large scale still requires additional in silico predictions. Here, we introduce TMVisDB to sieve through millions of predicted structures for TMPs. This resource enables both browsing through 46 million predicted TMPs and visualizing them along with their topological annotations without having to tap into costly predictions of the AlphaFold3-style. TMVisDB joins AlphaFoldDB structure predictions and transmembrane topology predictions from the protein language model (pLM) based method TMbed. We showcase the utility of TMVisDB for the analysis of proteins through two use cases, namely the B-lymphocyte antigen CD20 (Homo sapiens) and the cellulose synthase (Novosphingobium sp. P6W). We demonstrate the value of TMVisDB for large-scale analyses through findings pertaining to all TMPs predicted for the human proteome. TMVisDB is freely available at https://tmvisdb.rostlab.org.
We report the geometry, kinetic energy, and some optical properties of the 6,6,12-graphyne-based systems. We obtained the values of their binding energies and structural characteristics such as bond lengths and valence angles. Moreover, using nonorthogonal tight-binding molecular dynamics, we carried out a comparative analysis of the thermal stability of 6,6,12-graphyne-based isolated fragments (oligomer) and two-dimensional crystals constructed on its basis in a wide temperature range from 2500 to 4000 K. We found the temperature dependence of the lifetime for the finite graphyne-based oligomer as well as for the 6,6,12-graphyne crystal using a numerical experiment. From these temperature dependencies, we obtained the activation energies and frequency factors in the Arrhenius equation that determine the thermal stability of the considered systems. The calculated activation energies are fairly high: 1.64 eV for the 6,6,12-graphyne-based oligomer and 2.79 eV for the crystal. It was confirmed that the thermal stability of the 6,6,12-graphyne crystal concedes only to traditional graphene. At the same time, it is more stable than graphene derivatives such as graphane and graphone. In addition, we present data on the Raman and IR spectra of the 6,6,12-graphyne, which will help distinguish it from the other carbon low-dimensional allotropes in the experiment.
Postoperative pulmonary complications in cardiac surgery patients occur in 10-35% of cases, depending on differences in their definition, patient characteristics and type of surgical intervention, most of them are associated with ineffective coughing and evacuation of bronchial secretions. To determine the effectiveness of stimulating the evacuation of bronchial secretions with the help of oscillating PEP therapy carried out during the first three days. A randomized prospective study of 60 adult patients after elective cardiac surgery was performed (Clinical Trials.gov. protocol number NCT05159401). Oscillatory PEP-therapy was performed in 30 patients using Acapella DHGreen device (SmithMedicalASD, USA) 10-12 hours after tracheal extubation 3 times a day for 3 days after surgery. The control group (30 patients). The inclusion criteria: age over 18 years, spontaneous breathing after tracheal extubation, clear consciousness and productive contact with the patient, the ability to maintain adequate gas exchange on the low-flow oxygen inhalation, adequate analgesia (<2 points of VAS). Exclusion criteria: the need for re-intubation and mechanical ventilation, non-invasive mask ventilation, high-flow oxygen therapy, acute cerebrovascular accident, ongoing bleeding, cardiac insufficiency (inotropic index >10), shocks syndrome of various etiologies, the use of any extracorporeal support, any neuromuscular disorders, pneumothorax, hydro-or hemothorax. Before each session and 20 minutes after its end, when breathing air, blood oxygen saturation was recorded using a pulse oximeter (SpO2), the maximum inspiratory capacity (MIC) was measured using a Coach-2 incentive spirometer from SmithsMedical and spirometry with a portable ultrasonic spirometer Spiro Scout (Schiller, Switzerland). For the purposes of this work, the total index of the spirometry maximum inspiratory capacity (SMIC) was used - the sum of the respiratory volume and the reserve volume of inspiration in ml. Difficulties in evacuation of sputum were noted in 90% of patients. Three-day sessions of oscillating PEP- therapy are accompanied by a significant improvement in the passage of sputum, as evidenced by a 3-fold increase in the number of patients with productive cough. The increase in MIC in the main group was 46.9% and 21.3%, respectively (p=0.042), and the number of patients with values greater than MICo. 1500 ml increased from 23.3% to 7.6% (p<0.001). The effectiveness of oscillatory PEP-therapy is confirmed by a 7-fold decrease in the frequency of radiological changes in the lungs at the end of sessions (p<0.001), while in the control group the frequency of their occurrence practically did not change and remained at a high level. The total number of patients with respiratory insufficiency (SpO2≤92%) decreased by 8.6 times after completion of all PEP- therapy sessions (p=0.001), however, without statistically significant difference with the control group. Oscillatory PEP- therapy in cardiac surgery patients has a positive effect on sputum passage, ventilation parameters and oxygenating lung function. The procedure was well tolerated and there were no complications associated with it. Послеоперационные легочные осложнения у кардиохирургических больных встречаются в 10—35% случаев в зависимости от различий в их определении, особенностей пациентов и вида хирургического вмешательства; большинство из них связано с неэффективным кашлевым толчком и эвакуацией бронхиального секрета. Определить эффективность стимулирования эвакуации бронхиального секрета с помощью осцилляторной респираторной терапии с положительным давлением на выдохе (PEP-терапии), проводимой в течение первых трех суток, для восстановления функционального состояния легких и профилактики развития легочных осложнений у больных после больших реконструктивных кардиохирургических операций. Выполнялся рандомизированный проспективный набор 60 пациентов после плановых кардиохирургических операций. Работа выполнена на основании протокола, зарегистрированного на ClinicalTrials.gov, номер протокола NCT05159401. Осцилляторную PEP-терапию (30 больных) проводили с помощью спиротренажера (Acapella DHGreen, SmithMedicalASD, США) через 10—12 ч после экстубации трахеи в утреннее, дневное и вечернее время в течение 3 сут после операции. Контрольную группу (30 человек) составили пациенты, которым не проводились методы респираторной терапии, а исследования функции внешнего дыхания и показатели газообмена выполнены в 1-е сутки послеоперационного периода и в конце третьих суток после окончания операции. Критерии включения: возраст старше 18 лет, самостоятельное дыхание после экстубации трахеи, возможность поддержания адекватного газообмена на фоне ингаляции кислорода, ясное сознание и продуктивный контакт с пациентом, адекватное обезболивание (≤2 баллов) по 10-балльной визуально-аналоговой шкале боли (ВАШ). Критерии исключения: необходимость проведения ИВЛ, неинвазивной масочной вентиляции легких или высокопоточной оксигенотерапии, острое нарушение мозгового кровообращения, шоки различной этиологии, продолжающееся кровотечение, экстракорпоральные методы детоксикации, любые нервно-мышечные заболевания, пневмоторакс, гидро- или гемоторакс. Перед каждым сеансом и через 20 минут после его окончания при дыхании воздухом регистрировали насыщение крови кислородом по пульсоксиметру (SpO2), измеряли максимальную емкости вдоха (МЕВд) с помощью побудительного спирометра Coach-2 фирмы SmithsMedical, США и спирометрию портативным ультразвуковым спиирометром Spiro Scout (Schiller, Швейцария). Для целей данной работы использовался суммарный показатель максимальной емкости вдоха (СМЕВд) — сумма дыхательного объема и резервного объема вдоха в мл. Затруднения эвакуации мокроты отмечено у 90% больных. Проведение трехдневных процедур осцилляторной PEP-терапии сопровождалось значительным улучшением пассажа мокроты, о чем свидетельствовало увеличение в 3 раза числа пациентов с продуктивным кашлем. Прирост МЕВд в основной группе составил в 46,9 и 21,3% соответственно (p=0,042), а число пациентов со значениями более МЕВд 1500 мл возросло с 23,3 до 76,6% (p<0,001). Эффективность осцилляторной PEP-терапии подтверждалось снижением в 7 раз частоты рентгенологических изменений в легких по окончании процедур (p<0,001), в то время как в контрольной группе частота встречаемости их практически не изменилась и оставалась на высоком уровне. Общее количество больных с дыхательной недостаточностью (SpO2≤92%) после завершения всех процедур PEP-терапии уменьшилось в 8,6 раза (p=0,001), однако без достоверной разницы с контрольной группой. Осцилляторная PEP-терапия у кардиохирургических больных положительно влияет на пассаж мокроты, вентиляционные показатели и оксигенирующую функцию легких, причем наиболее выраженный эффект наблюдается у пациентов с дыхательной недостаточностью. Отмечена хорошая переносимость процедуры и отсутствие связанных с ней осложнений.
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Postoperative complications in cardiovascular surgery remain an important unresolved problem, in particular in patients with aortic aneurysm. The role of the altered microbiota in such patients is of great interest. The aim of this pilot study was to determine whether the development of postoperative complications in patients with aortic aneurysm is related with initial or acquired disorders of microbiota metabolism by monitoring the level of some aromatic microbial metabolites (AMMs) circulating in the blood before the surgery and in the early postoperative period. The study comprised patients with aortic aneurysm (n = 79), including patients without complications (n = 36) and patients with all types of complications (n = 43). The serum samples from the patients were collected before and 6 h after the end of the surgery. The most significant results were obtained for the sum of three sepsis-associated AMMs. This level was higher before the surgery in comparison with that of healthy volunteers (n = 48), p < 0.001, and it was also higher in the early postoperative period in patients with all types of complications compared to those without complications, p = 0.001; the area under the ROC curve, the cut-off value, and the odds ratio were 0.7; 2.9 µmol/L, and 5.5, respectively. Impaired microbiota metabolism is important in the development of complications after complex reconstructive aortic surgery, which is the basis for the search for a new prevention strategy.
A key problem in systems biology is the discovery of regulatory mechanisms that drive phenotypic behaviour of complex biological systems in the form of multi-level networks. Modern multi-omics profiling techniques probe these fundamental regulatory networks but are often hampered by experimental restrictions leading to missing data or partially measured omics types for subsets of individuals due to cost restrictions. In such scenarios, in which missing data is present, classical computational approaches to infer regulatory networks are limited. In recent years, approaches have been proposed to infer sparse regression models in the presence of missing information. Nevertheless, these methods have not been adopted for regulatory network inference yet. In this study, we integrated regression-based methods that can handle missingness into KiMONo, a Knowledge guided Multi-Omics Network inference approach, and benchmarked their performance on commonly encountered missing data scenarios in single- and multi-omics studies. Overall, two-step approaches that explicitly handle missingness performed best for a wide range of random- and block-missingness scenarios on imbalanced omics-layers dimensions, while methods implicitly handling missingness performed best on balanced omics-layers dimensions. Our results show that robust multi-omics network inference in the presence of missing data with KiMONo is feasible and thus allows users to leverage available multi-omics data to its full extent.
Cosmetic tattooing of eyebrow and lips has become very popular and is expected to be paralleled by more frequent complications. We present 4 cases of granulomas in cosmetic tattoos complicated by regional or systemic manifestations of sarcoidosis including affection of the lungs in 2 cases, the activity triggered by the tattoo. Three cases of traditional decorative tattoos on extremities serve as reference. It is noteworthy that cosmetic tattoos despite small size and thereby low relative dose of pigment injected in the skin can trigger fully developed systemic sarcoidosis. It is hypothesized that iron oxide pigments popular in cosmetic tattoo inks of red or brown color may be prone to elicit sarcoid reactions and thus carry a special risk of granuloma. In decorative tattoos, carbon black is the commonest trigger. It is emphasized that the finding of granulomas in tattoos shall be followed by search of other manifestations of sarcoidosis through patient history and diagnostic examinations to exclude pulmonary, ocular, and other organ manifestations. Patients with granulomas in tattoos shall be informed that active sarcoidosis, if not already present, can become manifest later with a latency of months or years and often with abrupt debut when the triggering tattoo may be overlooked by the doctor who is unfamiliar with this less common type of sarcoidosis.
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We consider a linear enhanced viscoelastic continuum of general nature but of specific type. Namely, we consider a reduced elastic continuum, satisfying Lagrange equations, where the strain energy depends on a certain (special) vectorial generalized coordinate, but does not depend on its gradient, and then add linear dissipation to the existing elastic connections. We may also represent this model as a 'bearing continuum', where all the connections are present (described by one vectorial generalized coordinate), enriched in each point by a 'distributed dynamic absorber' (described by 'special' vectorial generalized coordinate). We look for free harmonic waves in this infinite medium and obtain a reduced spectral problem for the vectorial generalized coordinate of the bearing continuum, for an arbitrary number of degrees of freedom. It was shown earlier that under certain symmetry conditions in the elastic case we obtain a single negative acoustic metamaterial, i.e. a medium that has band gaps. Further, we consider isotropic and gyrotropic reduced media, described by two three-dimensional vectorial generalized coordinates. First, we generalize results of previous studies for more complex elastic coupling, discovering a polarized shear wave, which has both bandgaps and zones of anomalous refraction. Then we introduce linear dissipation of different kinds. We find that viscosity yields in existence of travelling harmonic waves for all frequencies, possibly except for some points. Logarithmic decrement, infinite for the elastic material in bandgaps, becomes finite and decreases as the dissipation increases, at least for small viscosity. An important observation is: an infinitesimal dissipation in most cases transforms bandgaps into zones of travelling evanescent waves that partially are zones of anomalous refraction (decreasing parts of dispersion curves), where the medium is a double negative acoustic metamaterial. This article is part of the theme issue 'Wave generation and transmission in multi-scale complex media and structured metamaterials (part 2)'.
SAPO-34 nanocrystals with sizes of 50-150 nm were obtained via steam-assisted crystallization (SAC) for 5 h at 200 °C from two types of aluminum precursors-aluminum isopropoxide and boehmite. A reaction mixture composition with a small amount of organic template tetraehylammonium hydroxide (TEAOH) was used with the molar ratio TEAOH/Al2O3 = 1/1. The alumina precursor type and duration of the SAC (5 and 24 h) on the crystal size, texture, and acid properties were investigated. The SAPO-34 nanocrystals that we obtained possess a large micropore volume of 0.22-0.24 cm3/g and a specific surface area of 651-695 m2/g. When the crystallization was prolonged for up to 24 h, a SAPO-18 structure appeared, but the micropore and mesopore volumes changed insignificantly. Using boehmite as the aluminum precursor led to higher mesoporosity of the material but a little bit lower acidity when compared with the samples prepared from aluminum isopropoxide. In addition, the method proposed was used for preparing a SAPO-34-coated aluminum adsorber heat exchanger. Thus, the synthesis method proposed is affordable and effective to prepare SAPO-34 highly crystalline nanoparticles, with no need for post-synthetic procedures as the mother liquor separation from nanocrystals.
Pancreatic carcinoma is a gastrointestinal malignancy with poor prognosis. Treatment with gemcitabine, the most potent chemotherapeutic against this cancer up to date, is not curative, and resistance may appear. Complementary treatment with an oncolytic virus, such as the rat parvovirus H-1PV, which is infectious but nonpathogenic in humans, emerges as an innovative option. To prove that combining gemcitabine and H-1PV in a model of pancreatic carcinoma may reduce the dosage of the toxic drug and/or improve the overall anticancer effect. Pancreatic tumors were implanted orthotopically in Lewis rats or subcutaneously in nude mice and treated with gemcitabine, H-1PV, or both according to different regimens. Tumor size was monitored by micro-computed tomography, whereas bone marrow, liver, and kidney functions were monitored by measuring clinically relevant markers. Human pancreatic cell lines and gemcitabine-resistant derivatives were tested in vitro for sensitivity to H-1PV infection with or without gemcitabine. In vitro studies proved that combining gemcitabine with H-1PV resulted in synergistic cytotoxic effects and achieved an up to 15-fold reduction in the 50% effective concentration of the drug, with drug-resistant cells remaining sensitive to virus killing. Toxicologic screening showed that H-1PV had an excellent safety profile when applied alone or in combination with gemcitabine. The benefits of applying H-1PV as a second-line treatment after gemcitabine included reduction of tumor growth, prolonged survival of the animals, and absence of metastases on CT-scans. In addition to their potential use as monotherapy for pancreatic cancer, parvoviruses can be best combined with gemcitabine in a two-step protocol.
Oncolytic virotherapy represents a recent approach to anticancer therapy. Rodent autonomous parvoviruses (PVs) represent naturally oncolytic viruses that are non-pathogenic for humans but possess and extended tropism, being capable of infecting transformed cells of both rodent and human origin. Recent work from our group demonstrate that PVs can act as direct lytic agents and adjuvants, stimulating antitumor immune responses against glioma and pancreatic ductal adenocarcinoma (PDAC).
The incidence of lymphomas developing in both immunocompetent and immunosuppressed patients continues to steadily increase worldwide. Current chemotherapy and immunotherapy approaches have several limitations, such as severe side toxicity and selection of resistant cell variants. Autonomous parvoviruses (PVs), in particular the rat parvovirus H-1PV, have emerged as promising anticancer agents. Although it is apathogenic in humans, H-1PV has been shown to infect and suppress various rat and human tumors in animal models. In this study, we demonstrate the capacity of H-1PV for efficiently killing, through necrosis, cell cultures originating from Burkitt's lymphoma (BL), while sparing normal B lymphocytes. The cytotoxic effect was generally accompanied by a productive H-1PV infection. Remarkably, parvovirus-based monotherapy efficiently suppressed established BL at an advanced stage in a severe combined immunodeficient (SCID) mouse model of the disease. The data show for the first time that an oncolytic parvovirus deserves further consideration as a potential tool for the treatment of some non-Hodgkin B-cell lymphomas, including those resistant to apoptosis induction by rituximab.
The genus Helicobacter contains more than 35 species. Helicobacter pylori is the most important in terms of human health. Discovery of these helicobacters gives opportunity to understand the relationship between these bacteria which colonise the animal and human gut and their effect on the host. Infection with Helicobacter spp. and the associated diseases in their hosts allow us to study the pathogenic mechanisms. The potential zoonotic pathway for the transmission of Helicobacter spp. and epidemiology of this genus, deserve more attention to these emerging pathogens.