Click chemistry was extensively used to decorate synthetic multivalent scaffolds with glycans to mimic the cell surface glycocalyx and to develop applications in glycosciences. Conjugation methods ...such as oxime ligation, copper(
i
)-catalyzed alkyneazide cycloaddition, thiolene coupling, squaramide coupling or Lansbury aspartylation proved particularly suitable to achieve this purpose. This review summarizes the synthetic strategies that can be used either in a stepwise manner or in an orthogonal one-pot approach, to conjugate multiple copies of identical or different glycans to cyclopeptide scaffolds (namely multivalent glycocyclopeptides) having different size, valency, geometry and molecular composition. The second part of this review will describe the potential of these structures to interact with various carbohydrate binding proteins or to stimulate immunity against tumor cells.
In this review, we describe the conjugation methods used to construct multivalent glycocyclopeptides and their utilization for applications in glycoscience.
Despite the growing popularity of machine learning models in the cyber-security applications (e.g., an intrusion detection system (IDS)), most of these models are perceived as a black-box. The ...eXplainable Artificial Intelligence (XAI) has become increasingly important to interpret the machine learning models to enhance trust management by allowing human experts to understand the underlying data evidence and causal reasoning. According to IDS, the critical role of trust management is to understand the impact of the malicious data to detect any intrusion in the system. The previous studies focused more on the accuracy of the various classification algorithms for trust in IDS. They do not often provide insights into their behavior and reasoning provided by the sophisticated algorithm. Therefore, in this paper, we have addressed XAI concept to enhance trust management by exploring the decision tree model in the area of IDS. We use simple decision tree algorithms that can be easily read and even resemble a human approach to decision-making by splitting the choice into many small subchoices for IDS. We experimented with this approach by extracting rules in a widely used KDD benchmark dataset. We also compared the accuracy of the decision tree approach with the other state-of-the-art algorithms.
During cytokinesis, as dividing animal cells pull apart into two daughter cells, the final stage, termed abscission, requires breakage of the midbody, a thin membranous stalk connecting the daughter ...cells. This membrane fission event topologically resembles the budding of viruses, such as HIV-1, from infected cells. We found that two proteins involved in HIV-1 budding--tumor susceptibility gene 101 (Tsg101), a subunit of the endosomal sorting complex required for transport I (ESCRT-I), and Alix, an ESCRT-associated protein--were recruited to the midbody during cytokinesis by interaction with centrosome protein 55 (Cep55), a centrosome and midbody protein essential for abscission. Tsg101, Alix, and possibly other components of ESCRT-I were required for the completion of cytokinesis. Thus, HIV-1 budding and cytokinesis use a similar subset of cellular components to carry out topologically similar membrane fission events.
The vast expansion in recent years of the cellular processes promoted by the endosomal sorting complex required for transport (ESCRT) machinery has reinforced its identity as a modular system that ...uses multiple adaptors to recruit the core membrane remodelling activity at different intracellular sites and facilitate membrane scission. Functional connections to processes such as the aurora B-dependent abscission checkpoint also highlight the importance of the spatiotemporal regulation of the ESCRT machinery. Here, we summarise the role of ESCRTs in viral budding, and what we have learned about the ESCRT pathway from studying this process. These advances are discussed in the context of areas of cell biology that have been transformed by research in the ESCRT field, including cytokinetic abscission, nuclear envelope resealing and plasma membrane repair.
Background
Selective reactions to clavulanic acid (CLV) account for around 30% of immediate reactions after administration of amoxicillin‐CLV. Currently, no immunoassay is available for detecting ...specific IgE to CLV, and its specific recognition in patients with immediate reactions has only been demonstrated by basophil activation testing, however with suboptimal sensitivity. The lack of knowledge regarding the structure of the drug that remains bound to proteins (antigenic determinant) is hampering the development of in vitro diagnostics. We aimed to identify the antigenic determinants of CLV as well as to evaluate their specific IgE recognition and potential role for diagnosis.
Methods
Based on complex CLV degradation mechanisms, we hypothesized the formation of two antigenic determinants for CLV, AD‐I (N‐protein, 3‐oxopropanamide) and AD‐II (N‐protein, 3‐aminopropanamide), and designed different synthetic analogs to each one. IgE recognition of these structures was evaluated in basophils from patients with selective reactions to CLV and tolerant subjects. In parallel, the CLV fragments bound to proteins were identified by proteomic approaches.
Results
Two synthetic analogs of AD‐I were found to activate basophils from allergic patients. This determinant was also detected bound to lysines 195 and 475 of CLV‐treated human serum albumin. One of these analogs was able to activate basophils in 59% of patients whereas CLV only in 41%. Combining both results led to an increase in basophil activation in 69% of patients, and only in 12% of controls.
Conclusion
We have identified AD‐I as one CLV antigenic determinant, which is the drug fragment that remains protein‐bound.
The ability of synthetic determinants of clavulanic acid (CLV) to activate basophils from patients with immediate reactions to this drug is influenced by the chemical structure and their reactivity to proteins. Antigenic determinant‐I (AD‐I) has been identified as the fragment of the clavulanic acid structure that remains linked to the protein, which corresponds to the synthetic analogs (Clav2 and Clav3) able to activate basophils. This synthetic determinant analog to AD‐I, with ability to bind proteins, can activate basophils in a higher proportion of patients compared to the native drug, clavulanic acid.
The endosomal sorting complex required for transport (ESCRT) machinery is a set of cellular protein complexes required for at least three topologically equivalent membrane scission events, namely ...multivesicular body (MVB) formation, retroviral particle release and midbody abscission during cytokinesis. Recently, several studies have explored the mechanism by which the core ESCRT‐III subunits mediate membrane scission and might be differentially required according to the functions of the pathway. In this review, we discuss the links between the ESCRT machinery and cytokinesis, with special focus on abscission initiation and regulation.
Wearing face masks has become a usual practice in acute infection events inducing the problem of misinterpreting the emotions of others. Empirical evidence about face masks mainly relies on adult ...data, neglecting, for example, school kids who firmly are dependent on effective nonverbal communication. Here we offer insights from a joint school–university project. Data indicate that emotional reading of 9 to 10 years old pupils (N = 57) was similarly impaired as adults on an overall performance level, but that their selective performance on specific emotions was quite different. Kids showed extreme problems in reading the emotion disgust, strong effects on fear and sadness, and only mild effects on happiness, but also even better performances for emotional states anger and neutral when faces were masked. This project did gain not only relevant data about children’s perception but also made clear how fruitful seriously conducted school projects can be to encourage the interest and commitment for Science, Technology, Engineering, and Mathematics (STEM)-relevant topics.
Recently, antimicrobial peptides (AMPs), also called host defence peptides (HDPs), are attracting great interest, as they are a highly viable alternative in the search of new approaches to the ...resistance presented by bacteria against antibiotics in infectious diseases. However, due to their nature, they present a series of disadvantages such as low bioavailability, easy degradability by proteases, or low solubility, among others, which limits their use as antimicrobial agents. For all these reasons, the use of vehicles for the delivery of AMPs, such as polymers, nanoparticles, micelles, carbon nanotubes, dendrimers, and other types of systems, allows the use of AMPs as a real alternative to treatment with antibiotics.
The Internet as we know it today is the result of a continuous activity for improving network communications, end user services, computational processes and also information technology ...infrastructures. The Internet has become a critical infrastructure for the human-being by offering complex networking services and end-user applications that all together have transformed all aspects, mainly economical, of our lives. Recently, with the advent of new paradigms and the progress in wireless technology, sensor networks and information systems and also the inexorable shift towards everything connected paradigm, first as known as the Internet of Things and lately envisioning into the Internet of Everything, a data-driven society has been created. In a data-driven society, productivity, knowledge, and experience are dependent on increasingly open, dynamic, interdependent and complex Internet services. The challenge for the Internet of the Future design is to build robust enabling technologies, implement and deploy adaptive systems, to create business opportunities considering increasing uncertainties and emergent systemic behaviors where humans and machines seamlessly cooperate.
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