Stages Of Cycle Research Articles

Important antiviral properties of Streptomyces species compounds

species, a subgroup of Actinomycetes bacteria, have been analysed for their antiviral properties. These bioactive secondary metabolites, which have a broad spectrum of chemical structures and strong biological activity, offer a promising opportunity for new antiviral therapeutics against various viral infections. These metabolites target different stages of viral replication or interactions with host cells, making them important for biological research and pharmaceutical development. bacteria contain numerous antiviral mechanisms that inhibit viral infections at different stages of the viral life cycle. and other actinomycetes can improve the health of people with viruses, and recent research suggests that combining with other bacterial species could improve overall health and regulate infections. This emphasises the importance of comprehensive approaches to combating viral infections and research into natural products. Further research into multispecies combinations of and other bacterial species is needed to fully utilise their therapeutic potential against viral diseases.

СОВЕРШЕНСТВОВАНИЕ СИСТЕМЫ РЕМОНТА И ТЕХНИЧЕСКОГО ОБСЛУЖИВАНИЯ ПАССАЖИРСКИХ ВАГОНОВ ДАЛЬНЕГО СООБЩЕНИЯ

The existing systems of maintenance and scheduled preventive maintenance of passenger rolling stock used for long-distance passenger traffic with speeds up to 140 km/h are considered. Promising areas for their improvement are identified. A combined repair system is proposed, which provides a uniform approach of the rolling stock to the position of a single technical audit and scheduled preventive maintenance without taking into account its mileage. The replacement of the element base, when the mileage criteria are met, is carried out on repair and equipment tracks or specially equipped positions during the technical preparation of the rolling stock at the initial point. The proposed system, in comparison with existing ones, reduces the need for depot repairs; the cost of carrying out scheduled repairs of cars, the time spent by cars in an idle fleet, and also provides opportunities for additional operation of the car at the operational stage of the life cycle. Also, the proposed system allows regulating the frequency of the element base replacement of passenger cars with a designated service life of 40 years, including them in the mandatory requirements for the necessary periodic replacement during capital repairs of the car every 5 years.

Microscopic and molecular genetic analyses of morphological development of the actinomycete Actinoplanes missouriensis.

The survival strategy of members of the bacterial genus Actinoplanes is fascinating from morphological and evolutionary perspectives. A brief motile phase is incorporated in the filamentous and resting stages of the life cycle of Actinoplanes missouriensis. Spores either lie dormant or swim under different external conditions. This review presents microscopic observations and molecular genetic analyses of A. missouriensis morphological development. Selected examples of the characterization of developmental genes and their products are also introduced.

Evidence-based practice in canine artificial insemination.

A number of methods are currently used to predict the optimal date of insemination of the breeding bitch, particularly with the use of frozen-thawed canine semen which has a far shorter lifespan than fresh semen. Aside from confirming cytological oestrus, vaginal cytology is of no assistance in predicting the most fertile day(s) in a bitch; however, a neglected avenue of research suggests that vaginal cytology may be of great importance in confirming the days of optimal fertility retrospectively. Similarly, vaginoscopy provides clues as to the stage of a bitch's cycle but is inadequate as a sole determinant of her most fertile days. Nevertheless, vaginoscopy is useful to identify very late oestrus and the onset of dioestrus, as well as Stage I of labour (cervical dilatation). Due to variations in the rate at which circulating progesterone concentrations rise in individual bitches, the reliability of circulating progesterone concentrations for determining the optimal day(s) of insemination with frozen-thawed semen decreases as values rise. Moreover, progesterone assay results can vary widely due to extrinsic factors such as the time of blood sampling, sample storage conditions and the assay employed. Finally, this review investigates evidence surrounding various insemination routes and suggests that well-performed vaginal insemination, even with frozen-thawed semen, may be an acceptable approach for cases where transcervical insemination is impractical.

Polymorphism of spore germination receptor genes in Bacillus anthracis strains of major genetic lineages

Introduction. The genetic structure of the global population of Bacillus anthracis characterized by an unequal distribution of isolates of the main genetic lineages A, B and C, the reason for which is unknown. Determining the characteristics of genes encoding factors that determine the existence of this pathogen at the intra- and extra organismal stages of the life cycle, which can influence the prevalence of strains, is relevant. Aim — сharacterization of the genes and proteins of spore germination in strains of the anthrax pathogen of different genetic lineages. Materials and methods. Whole genome sequences of 46 B. anthracis strains and the CI strain of B. cereus biovar anthracis from the NCBI GenBank database studied. In silico analysis carried out using the programs “BLASTn”, “MEGA X”, “Tandem Repeat Finder”. Results. The number of SNPs, indels and pseudogenes in B. anthracis strains of line B was 2,7–25,6 times higher, in line C 2–23,5 times, and in the B. cereus biovar anthracis strain was 20–2841 times higher than in strains of line A. Significant substitutions in genes leading to changes in the amino acid composition of 10 germination receptor proteins were also significantly more common in B. anthracis strains of lines B, C and the B. cereus biovar anthracis strain. Undescribed VNTRs within the gerHA gene with repeat units of 78 and 117 bp identified, varying between and within isolates of different genetic lineages. Six germination receptor genes have been shown to have rare starting codons. Conclusion. A larger number of non-synonymous SNPs in the genes of spore germination receptors with changes in the amino acid composition of proteins in B. anthracis strains of the main genetic lines B, C and B. cereus biovar anthracis than in strains of line A suggests their limited adaptive capabilities and may be one of the explanations for the lower prevalence compared to line A. Differences in the gerHA and gerM genes make it possible to differentiate the major B and C genetic lineages from A.

CcdC Regulates Biofilm Dispersal in Bacillus velezensis FZB42

Bacillus velezensis FZB42 is a plant growth-promoting rhizobacterium (PGPR) and a model microorganism for biofilm studies. Biofilms are required for the colonization and promotion of plant growth in the rhizosphere. However, little is known about how the final stage of the biofilm life cycle is regulated, when cells regain their motility and escape the mature biofilm to spread and colonize new niches. In this study, the non-annotated gene ccdC was found to be involved in the process of biofilm dispersion. We found that the ccdC-deficient strain maintained a wrinkled state at the late stage of biofilm formation in the liquid—gas interface culture, and the bottom solution showed a clear state, indicating that no bacterial cells actively escaped, which was further evidenced by the formation of a cellular ring (biofilm pellicle) located on top of the preformed biofilm. It can be concluded that dispersal, a biofilm property that relies on motility proficiency, is also positively affected by the unannotated gene ccdC. Furthermore, we found that the level of cyclic diguanylate (c-di-GMP) in the ccdC-deficient strain was significantly greater than that in the wild-type strain, suggesting that B. velezensis exhibits a similar mechanism by regulating the level of c-di-GMP, the master regulator of biofilm formation, dispersal, and cell motility, which controls the fitness of biofilms in Pseudomonas aeruginosain. In this study, we investigated the mechanism regulating biofilm dispersion in PGPR.

Pseudovirus-Based Systems for Screening Natural Antiviral Agents: A Comprehensive Review

Since the outbreak of COVID-19, researchers have been working tirelessly to discover effective ways to combat coronavirus infection. The use of computational drug repurposing methods and molecular docking has been instrumental in identifying compounds that have the potential to disrupt the binding between the spike glycoprotein of SARS-CoV-2 and human ACE2 (hACE2). Moreover, the pseudovirus approach has emerged as a robust technique for investigating the mechanism of virus attachment to cellular receptors and for screening targeted small molecule drugs. Pseudoviruses are viral particles containing envelope proteins, which mediate the virus’s entry with the same efficiency as that of live viruses but lacking pathogenic genes. Therefore, they represent a safe alternative to screen potential drugs inhibiting viral entry, especially for highly pathogenic enveloped viruses. In this review, we have compiled a list of antiviral plant extracts and natural products that have been extensively studied against enveloped emerging and re-emerging viruses by pseudovirus technology. The review is organized into three parts: (1) construction of pseudoviruses based on different packaging systems and applications; (2) knowledge of emerging and re-emerging viruses; (3) natural products active against pseudovirus-mediated entry. One of the most crucial stages in the life cycle of a virus is its penetration into host cells. Therefore, the discovery of viral entry inhibitors represents a promising therapeutic option in fighting against emerging viruses.

TECHNOLOGIES FOR ASSESSING THE OPERATIONAL QUALITY OF INDUSTRIAL BUILDINGS AS A CONSEQUENCE OF PARTIAL MILITARY DESTRUCTION

Purpose. Research conducted in the direction of operational quality proves that the life cycle of construction products can also be significantly increased due to the use of the latest technologies of a complex technical approach. The complex technical approach covers the principles of using the latest technologies, which compensate for the functional costs of the object at the stage of operation. As part of the latest technologies, the modern world requires the presence of developments that effectively save resources and at the same time ensure the required level of security in various crisis situations, including during a state of war. The main purpose of implementing this approach is to establish the reasons for the loss of reliability and resource when accounting for changes in the conditions of the external and internal environment. Methodology. Methods and techniques for diagnosing the reliability and operational quality of construction objects make it possible to implement assessment procedures at various stages of the life cycle, including during the current period, in previous design cycles (prototype search stages), as well as comparative and analytical comparison with analogues . The results of the implementation make it possible to identify the promising direction of normalization of construction projects, to substantiate and develop technologies for the formation of its operational quality. Findings. The situation of the physical state of the industrial building due to military destruction is analyzed, after which the search for optimization technologies in the formation of reliability and operational quality of construction objects, including for the effective implementation of investment and construction projects, is substantiated and proposed. Originality. Adaptation approaches of timely response in emergency conditions, in order to comply with the planned standards of operational quality, are substantiated, implemented on the practical example of the implementation of the technical report of the production and mechanical building No. 132, located in the city of Zaporizhzhia, SE "Ivchenko-Progress" 63T-1286-OB – TK after military destruction. Practical value. Adaptation approaches of timely response in emergency conditions, in order to comply with the planned standards of operational quality, are substantiated, implemented on the practical example of the implementation of the technical report of the production and mechanical building No. 132, located in the city of Zaporizhzhia, SE "Ivchenko-Progress" 63T-1286-OB – TK after military destruction. Conclusions. The results of scientific and practical research made it possible to reveal the actual principles of management technologies, evaluation and methods of improving operational quality at all stages of the life cycle of a construction object, taking into account risky and dangerous situations during military operations. This technical report was prepared on the basis of the performed visual and instrumental research of construction structures of the industrial building. The decision of the scientific group of experts established that the operation of the object under study should be stopped until its operational suitability is restored in accordance with the proposed recommendations in accordance with the project documentation. The scientific and practical significance of the study justifies the need for further application of the latest technologies of the complex technical approach in the formation of operational quality for the effective implementation of investment and construction projects.

Effect on the splenocyte function of weaned piglets induced by continuous lipopolysaccharide injections

Abstract Introduction When piglets are exposed to pathogens for a long period, the immune system organs, among them the spleen, play a major role in combating the stress caused by those pathogens. In the present study, the effect on splenocyte function was investigated in a model of weaned piglets in which stress was induced by multiple low doses of lipopolysaccharide (LPS). Material and Methods Forty-eight 28-day-old piglets were divided into two groups: the LPS group and the control group. During the experimental period of thirteen days, the LPS group was intraperitoneally injected with LPS (100 μg/kg) once per day, and the control group was injected with the same volume of 0.9% sterile saline. On the 1st, 5th, 9th and 13th days, the piglets’ spleens were collected for isolating splenocytes. The proliferation ability of splenocytes was evaluated by the cell-counting-kit 8 method. Flow cytometry was used to detect cell cycle stage and apoptosis, and the nitric oxide level of cell supernatant was also tested. Results In the experimental group, the proliferation ability of splenocytes was enhanced, the proportion of cells in the G0/G1 phase was smaller, and cells were promoted to the S and G2/M phases. Meanwhile, apoptosis was suppressed and nitric oxide release upregulated. The results were significantly different between the LPS group and the control group on the 5th and 9th days. Conclusion The difference between the results of one group and those of the other suggest that after the 5th LPS injection, multiple low doses of LPS activated splenocytes and restored the number of splenocytes, which maintained and possibly enhanced the regulation of the immune function of the spleen.

Sperm functionality is differentially regulated by porcine oviductal extracellular vesicles from the distinct phases of the estrous cycle.

Context Extracellular vesicles (EVs) derived from the oviductal fluid (oEVs) play a critical role in various reproductive processes, including sperm capacitation, fertilisation, and early embryo development. Aims To characterise porcine oEVs (poEVs) from different stages of the estrous cycle (late follicular, LF; early luteal, EL; mid luteal, ML; late luteal, LL) and investigate their impact on sperm functionality. Methods poEVs were isolated, characterised, and labelled to assess their binding to boar spermatozoa. The effects of poEVs on sperm motility, viability, acrosomal status, protein kinase A phosphorylation (pPKAs), tyrosine phosphorylation (Tyr-P), and in in vitro fertility were analysed. Key results poEVs were observed as round or cup-shaped membrane-surrounded vesicles. Statistical analysis showed that poEVs did not significantly differ in size, quantity, or protein concentration among phases of the estrous cycle. However, LF poEVs demonstrated a higher affinity for binding to sperm. Treatment with EL, ML, and LL poEVs resulted in a decrease in sperm progressive motility and total motility. Moreover, pPKA levels were reduced in presence of LF, EL, and ML poEVs, while Tyr-P levels did not differ between groups. LF poEVs also reduced sperm penetration rate and the number of spermatozoa per penetrated oocyte (P Conclusions poEVs from different stages of the estrous cycle play a modulatory role in sperm functionality by interacting with spermatozoa, affecting motility and capacitation, and participating in sperm-oocyte interaction. Implications The differential effects of LF and LL poEVs suggest the potential use of poEVs as additives in IVF systems to regulate sperm-oocyte interaction.

Synchronizing Drosophila larvae with the salivary gland reporter Sgs3-GFP for discovery of phenotypes in the late third instar stage.

The larval stage of the Drosophila melanogaster life cycle is characterized by rapid growth and nutrient storage that occur over three instar stages separated by molts. In the third instar, the steroid hormone ecdysone drives key developmental processes and behaviors that occur in a temporally-controlled sequence and prepare the animal to undergo metamorphosis. Accurately staging Drosophila larvae within the final third instar is critical due to the rapid developmental progress at this stage, but it is challenging because the rate of development varies widely across a population of animals even if eggs are laid within a short period of time. Moreover, many methods to stage third instar larvae are cumbersome, and inherent variability in the rate of development confounds some of these approaches. Here we demonstrate the usefulness of the Sgs3-GFP transgene, a fusion of the Salivary gland secretion 3 (Sgs3) and GFP proteins, for staging third instar larvae. Sgs3-GFP is expressed in the salivary glands in an ecdysone-dependent manner from the midpoint of the third instar, and its expression pattern changes reproducibly as larvae progress through the third instar. We show that Sgs3-GFP can easily be incorporated into experiments, that it allows collection of developmentally-equivalent individuals from a mixed population of larvae, and that its use enables precise assessment of changing levels of hormones, metabolites, and gene expression during the second half of the third instar.

Degradation of RC short beams under monotonic and repeated loads after cryogenic freeze-thaw cycles

ABSTRACT To investigate the effects of cryogenic freeze-thaw cycles and repeated loading on the bearing capacity and deformation properties of reinforced concrete (RC) short beams, RC short beams with different reinforcement ratios were subjected to Minus 160°C cryogenic freeze-thaw cycles. Subsequently, a four-point bending tests were carried out under monotonic and repeated loading with the aim of exploring the performance characteristics of the test beams, such as failure mode, load‐deflection response, and ductility. Experimental results showed that the failure mode of RC short beams changed from ductile bending to brittle shear failure after cryogenic freeze-thaw cycles. Additionally, the load-carrying capacity, deformation properties and energy dissipation performance exhibited a significant degradation trend. There is decreasing trend for the ductility and ultimate bearing capacity of beams with the increase in freeze-thaw cycles, and the decrease degree was most obvious in the first three cycles. Moreover, compared with monotonic loading, the ductility index of normal temperature beam and freeze-thaw cycle short beam decreased more significantly under repeated loading, and the bearing capacity decreases more obviously under the last stage of multi-level loading and unloading cycles.

Housing leverage, home value, and retirement

AbstractWe study the effect of housing leverage, measured using the loan‐to‐value (LTV) ratio, on homeowners' retirement decisions. We find that in general, elevated LTV ratios delay retirements. By decomposing the changes of the current LTV ratio into (1) equity extractions, (2) equity build‐up, (3) home value increases, and (4) home value decreases, we find that equity extractions and declining home value drive the negative relationship between housing leverage and retirement. In contrast, retirement decisions are less responsive to equity build‐up and home value appreciation. Our results suggest that the influence of housing leverage on retirement decisions is path‐dependent and asymmetric. We also find that transitions into retirement are more sensitive to home price declines, and retirement reversals are often triggered by equity extraction. Further analyses also reveal that the impact of housing leverage on retirement differs by household age and financial constraints, and it also varies across different stages of a housing market cycle.

DEVELOPMENT OF CLASSIFIERS OF DEVIATIONS FROM THE REQUIREMENTS OF REGULATORY DOCUMENTS OF THE OIL AND GAS INDUSTRY AND COMPENSATORY MEASURES

The paper analyzes the problem of ensuring safety at various stages of the life cycle of main pipelines and steel vertical tanks in cases of deviations from the requirements of current design standards. To effectively solve this problem, independent and easily modifiable classifiers of deviations from the requirements of regulatory documents, as well as measures aimed at compensating for these deviations, have been developed. The faceted method was chosen as the classification method, which allows us to divide a large object of study into smaller characteristics independent of each other, which facilitates the decision-making process and allows us to take into account many aspects.The resulting classifiers are a tool for systematization of information obtained during the analysis and development of special technical conditions necessary to ensure the safety of main pipelines and steel vertical tanks. Due to their ability to be easily modified, they can be adapted to specific objects and conditions, which makes them a versatile and flexible tool for developing and making engineering decisions.An important aspect of the work is the practical testing of the developed classifiers by applying them to a real object of the oil and gas industry. This stage of testing demonstrated the high efficiency and practical applicability of the proposed classifiers, which indicates their potential aimed at improving the safety of oil and gas transportation and storage facilities, as well as products of their processing.In addition, the systematization of information on deviations from the requirements of regulatory documents and ways to compensate for them allows not only to increase the level of safety during the construction, reconstruction and operation of pipelines and reservoirs, but also to reduce the consequences of possible emergencies.The results obtained represent an important step in the development of an approach to ensuring the safety of main pipelines and steel vertical tanks, and also have both practical and scientific value, and can be recommended for use by specialists in the field of design, technosphere safety and the development of special technical conditions.

Introducing the Occupational Health and Safety Potential Midpoint Impact Indicator in Social Life Cycle Assessment

Occupational health and safety (OSH) is crucial for sustainable development, recognized by corporations, the European Union, and Sustainable Development Goals. This study introduces a characterization model for OSH in the social life cycle assessment (S-LCA) to support the quantification of OHS along product supply chains and sustainable decision making. The characterization model aims to provide a practical approach for assessing OHS at the product level with actual working hours or recommends a secondary approach with monetary data, when working hours are unavailable, to calculate the Occupational Health and Safety Potential (OHSP). The developed model was tested in a theoretical case study on shirt production in Europe and globally. The case study shows that the European shirt value chain resulted in higher OHSP values than the global shirt values chain. In addition, the model shows which life cycle stages and organizations highly contributed to the OHSP results. In both approaches, the shirt production stage contributed highly. Differences in results emerged based on the calculation approach, underscoring the model’s versatility, because increasing the complexity of calculating the CFs with monetary values will affect the results based on sectorial monetary output. Additionally, the study mentions benefits to the operationalization of social impact assessment and limitations when the developed characterized model is employed. Last, this study aids in offering a tool for organizations to meet the demands of the new Corporate Sustainability Reporting Directive by quantifying and publicizing OHS data.

Problems of creating an effective system of health technology assessment at the early stages of the drug life cycle

Problems of creating an effective system of health technology assessment at the early stages of the drug life cycle

Abstract PO4-03-01: Enhancing Breast Cancer Subtyping: APIS Breast Cancer Subtyping Kit Proliferative Signature's Potential for Improved Proliferation Assessment and Recurrence Prediction

Abstract Background: Ki67, a widely recognized biomarker for measuring tumor cell proliferation in breast cancer (BC), plays a crucial role in classifying BC into luminal A and luminal B subtypes, subsequently aiding treatment decisions. However, the inconsistency in Ki67 assessment and the lack of standardization in methods and interpretation of immunohistochemistry (IHC) staining has hindered its recommendation for routine diagnostic use. The standardization of measurement techniques, especially for Ki67, holds immense potential for improving patient treatment outcomes. The APIS Breast Cancer Subtyping Kit (APIS BCS Kit) addresses these challenges by utilizing RT-qPCR to accurately determine the mRNA expression of BC markers, including Ki67, along with a novel four-gene proliferative signature, comprising four markers (MKI67, CCNA2, KIF23, and PCNA) associated with proliferation and expressed throughout all cell cycle stages, thereby providing a more accurate measure of tumor proliferation. In this study, we present the preliminary findings of our ongoing evaluation of the APIS BCS Kit proliferative signature's ability to distinguish between Luminal A and Luminal B subtypes and to determine the risk of recurrence in hormone receptor-positive (HR+) patients. Method: A total of N=153 retrospectively collected HR+/HER2 negative samples were provided by University of Basel. For each sample the following clinical annotations were included: relapse free survival, treatment regimen (Chemotherapy (ChT) or Hormone Therapy (HT)) as well as OncotypeDx (ODx) risk score (RS). N=40 samples underwent additional testing using PAM50 (Prosigna®) test. Only samples collected since 2018 were included, resulting in 10 observed relapse events (N=7 in HT cohort and N=3 in ChT cohort). RNA isolation from tissue sections and gene expression analysis were performed as per APIS BCS Kit instructions for use. The agreement of subtype calls between IHC, APIS BCS Kit, and PAM50 was assessed. The correlation between RS obtained from ODx, PAM50 and the APIS BCS Kit proliferation signature was also explored. Results: The agreement between IHC and the APIS BCS Kit subtype call, utilizing Ki67 alone as a measure of proliferation, was 67.3% (103/153). Replacing Ki67 with the APIS BCS Kit proliferation signature increased the concordance to 69.9% (107/153). The concordance between IHC and PAM50 subtype calls was comparable at 62.5% (25/40). The agreement between the APIS BCS Kit and PAM50 subtype call was notably higher (80%; 32/40). Significant association was observed between the APIS BCS Kit proliferation signature and ODx RS (P=.0001), and PAM50 RS (P=.002). In the HT cohort, both ODx and the APIS BCS Kit proliferation signature accurately predicted recurrence (by assigning high RS) in n=2 cases. In some cases both the APIS BCS Kit and ODx erroneously assigned low risk and subsequently missed n=4 recurrence events. Notably, APIS BCS Kit proliferation signature correctly identified one recurrence event (high RS), which was missed by ODx (low RS). Conclusion: The APIS Breast Cancer Subtyping Kit exhibits improved agreement with the PAM50 molecular subtype in contrast to the IHC-derived subtype, indicating that molecular testing may be a more suitable method for determining proliferation and distinguishing between luminal A and B subtypes. Furthermore, there is a significant correlation between the RS generated by APIS Breast Cancer Subtyping Kit proliferation signature and both PAM50 and Oncotype RS. These initial findings indicate that the APIS Breast Cancer Subtyping Kit proliferation signature has the potential to accurately identify patients at risk of recurrence, although additional studies including a larger proportion of events are needed to validate these results. Citation Format: Marcus Vetter, Anna Gasior, Elena-Diana Chiru, Joanna Gorniak, Leanne Gough, Mathew Harrison, Sara Rollinson, Simone Muenst, Christian Kurzeder. Enhancing Breast Cancer Subtyping: APIS Breast Cancer Subtyping Kit Proliferative Signature's Potential for Improved Proliferation Assessment and Recurrence Prediction [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-03-01.

Scorpion Venom Antimicrobial Peptide Derivative BmKn2-T5 Inhibits Enterovirus 71 in the Early Stages of the Viral Life Cycle In Vitro

Enterovirus 71 (EV71), a typical representative of unenveloped RNA viruses, is the main pathogenic factor responsible for hand, foot, and mouth disease (HFMD) in infants. This disease seriously threatens the health and lives of humans worldwide, especially in the Asia–Pacific region. Numerous animal antimicrobial peptides have been found with protective functions against viruses, bacteria, fungi, parasites, and other pathogens, but there are few studies on the use of scorpion-derived antimicrobial peptides against unenveloped viruses. Here, we investigated the antiviral activities of scorpion venom antimicrobial peptide BmKn2 and five derivatives, finding that BmKn2 and its derivative BmKn2-T5 exhibit a significant inhibitory effect on EV71. Although both peptides exhibit characteristics typical of amphiphilic α-helices in terms of their secondary structure, BmKn2-T5 displayed lower cellular cytotoxicity than BmKn2. BmKn2-T5 was further found to inhibit EV71 in a dose-dependent manner in vitro. Moreover, time-of-drug-addition experiments showed that BmKn2-T5 mainly restricts EV71, but not its virion or replication, at the early stages of the viral cycle. Interestingly, BmKn2-T5 was also found to suppress the replication of the enveloped viruses DENV, ZIKV, and HSV-1 in the early stages of the viral cycle, which suggests they may share a common early infection step with EV71. Together, the results of our study identified that the scorpion-derived antimicrobial peptide BmKn2-T5 showed valuable antiviral properties against EV71 in vitro, but also against other enveloped viruses, making it a potential new candidate therapeutic molecule.

CDK1-PP2A-B55 interplay ensures cell cycle oscillation via Apc1-loop300

Cell cycle control relies on a delicate balance of phosphorylation with CDK1 and phosphatases like PP1 and PP2A-B55. Yet, identifying the primary substrate responsible for cell cycle oscillations remains a challenge. We uncover the pivotal role of phospho-regulation in the anaphase-promoting complex/cyclosome (APC/C), particularly through the Apc1-loop300 domain (Apc1-300L), orchestrated by CDK1 and PP2A-B55. Premature activation of PP2A-B55 during mitosis, induced by Greatwall kinase depletion, leads to Apc1-300L dephosphorylation, stalling APC/C activity and delaying Cyclin B degradation. This effect can be counteracted using the B55-specific inhibitor pEnsa or by removing Apc1-300L. We also show Cdc20's dynamic APC/C interaction across cell cycle stages, but dephosphorylation of Apc1-300L specifically inhibits further Cdc20 recruitment. Our study underscores APC/C's central role in cell cycle oscillation, identifying it as a primary substrate regulated by the CDK-PP2A partnership.

Distinct life cycle stages of an ectosymbiotic DPANN archaeon.

DPANN archaea are a diverse group of microorganisms that are thought to rely on an ectosymbiotic lifestyle; however, the cell biology of these cell-cell interactions remains largely unknown. We applied live-cell imaging and cryo-electron tomography to the DPANN archaeon Nanobdella aerobiophila and its host, revealing two distinct life cycle stages. Free cells possess archaella and are motile. Ectobiotic cells are intimately linked with the host through an elaborate attachment organelle. Our data suggest that free cells may actively seek a new host, while the ectobiotic state is adapted to mediate intricate interaction with the host.