Binding of Plasmodium falciparum to CD36 can be shielded by the glycocalyx

Abstract Background Plasmodium falciparum-infected erythrocytes sequester in the microcirculation due to interaction between surface-expressed parasite proteins and endothelial receptors. Endothelial cells are covered in a carbohydrate-rich glycocalyx that shields against undesired leukocyte adhesion. It was investigated if the cellular glycocalyx affects the binding of P. falciparum-infected erythrocytes to CD36 in vitro. Methods Glycocalyx growth was followed in vitro by using azido sugars and cationized ferritin detecting O-glycoproteins and negatively charged proteoglycans, respectively. P. falciparum (clone FCR3/IT) was selected on Chinese hamster ovary (CHO) cells transfected with human CD36. Cytoadhesion to CHO CD36 at 1–4 days after seeding was quantified by using a static binding assay. Results The glycocalyx thickness of CHO cells increased during 4 days in culture as assessed by metabolic labelling of glycans with azido sugars and with electron microscopy studying the binding of cationized ferritin to cell surfaces. The functional importance of this process was addressed in binding assays by using CHO cells transfected with CD36. In parallel with the maturation of the glycocalyx, antibody-binding to CD36 was inhibited, despite stable expression of CD36. P. falciparum selected for CD36-binding recognized CD36 on CHO cells on the first day in culture, but the binding was lost after 2–4 days. Conclusion The endothelial glycocalyx affects parasite cytoadhesion in vitro, an effect that has previously been ignored. The previously reported loss of glycocalyx during experimental malaria may play an important role in the pathogenesis of malaria complications by allowing the close interaction between infected erythrocytes and endothelial receptors

Editorial: Ecology, Metabolism and Evolution of Archaea-Perspectives From Proceedings of the International Workshop on Geo-Omics of Archaea

To facilitate global efforts in addressing fundamental questions related to the biology of archaea, an international consortium of experts organized the International Workshop on Geo-Omics of Archaea (IWGOA), with the overarching themes of Ecology/Biogeochemistry, Metabolism, and Evolution. The IWGOA was held in Shenzhen, China, from October 25th to 27th, 2019. The meeting was attended by more than 200 attendees from China, Japan, USA, Australia, Germany, and France. Some of the most exciting oral and poster presentations made at the IWGOA are celebrated in this Research Topic Figure 1. The 21 manuscripts herein span different aspects of archaeal biology in both extreme and “non-extreme” environments in both marine and terrestrial settings and use a variety of approaches—community ecology, environmental lipidomics and genomics, organismal biology, and nucleic acid biochemistry—embodying diverse research thrusts that makes archaeal biology so exciting. At the same time, the manuscripts include over 100 authors from Asia, North America, and Europe, realizing our goal to engage a global audience in the biology of archaea

Hiding in Plain Sight: A Longitudinal Study of Combosquatting Abuse

Domain squatting is a common adversarial practice where attackers register domain names that are purposefully similar to popular domains. In this work, we study a specific type of domain squatting called "combosquatting," in which attackers register domains that combine a popular trademark with one or more phrases (e.g., betterfacebook[.]com, youtube-live[.]com). We perform the first large-scale, empirical study of combosquatting by analyzing more than 468 billion DNS records---collected from passive and active DNS data sources over almost six years. We find that almost 60% of abusive combosquatting domains live for more than 1,000 days, and even worse, we observe increased activity associated with combosquatting year over year. Moreover, we show that combosquatting is used to perform a spectrum of different types of abuse including phishing, social engineering, affiliate abuse, trademark abuse, and even advanced persistent threats. Our results suggest that combosquatting is a real problem that requires increased scrutiny by the security community.Comment: ACM CCS 1

Haplotypes of the Endothelial Protein C Receptor (EPCR) Gene are Not Associated with Severe Malaria in Tanzania.

Endothelial protein C receptor (EPCR) was recently identified as a key receptor for Plasmodium falciparum erythrocyte membrane protein 1 mediating sequestration of P. falciparum-infected erythrocytes in patients suffering from severe malaria. Soluble EPCR (sEPCR) inhibits binding of P. falciparum to EPCR in vitro and increased levels of sEPCR have been associated with the H3 haplotype of the EPCR encoding PROCR gene. It has been hypothesized that elevated sEPCR levels, possibly linked to the PROCR H3 genetic variant, may confer protection against severe forms of malaria. This study determined the frequencies of PROCR haplotypes H1-4 and plasma levels of sEPCR in a Tanzanian study population to investigate a possible association with severe malaria. Study participants were children under 5 years of age admitted at the Korogwe District Hospital (N = 143), and diagnosed as having severe malaria (N = 52; including cerebral malaria N = 17), uncomplicated malaria (N = 24), or an infection other than malaria (N = 67). In addition, blood samples from 71 children living in nearby villages were included. The SNPs defining the haplotypes of PROCR gene were determined by post-PCR ligation detection reaction-fluorescent microsphere assay. Individuals carrying at least one H3 allele had significantly higher levels of sEPCR than individuals with no H3 alleles (P < 0.001). No difference in the frequency of H3 was found between the non-malaria patients, malaria patients or the village population (P > 0.1). Plasma levels of sEPCR differed between these three groups, with higher sEPCR levels in the village population compared to the hospitalized patients (P < 0.001) and higher levels in malaria patients compared to non-malaria patients (P = 0.001). However, no differences were found in the distribution of H3 (P = 0.2) or levels of sEPCR (P = 0.8) between patients diagnosed with severe and uncomplicated malaria. Frequencies of SNPs determining PROCR haplotypes were in concordance with other African studies. The PROCR H3 allele was associated with higher levels of sEPCR, confirming earlier findings, however, in this Tanzanian population; neither PROCR haplotype nor level of sEPCR was associated with severe malaria, however, larger studies are needed to confirm these findings

Pay Less for Your Privacy: Towards Cost-Effective On-Chain Mixers

On-chain mixers, such as Tornado Cash (TC), have become a popular privacy solution for many non-privacy-preserving blockchain users. These mixers enable users to deposit a fixed amount of coins and withdraw them to another address, while effectively reducing the linkability between these addresses and securely obscuring their transaction history. However, the high cost of interacting with existing on-chain mixer smart contracts prohibits standard users from using the mixer, mainly due to the use of computationally expensive cryptographic primitives. For instance, the deposit cost of TC on Ethereum is approximately $1.1m$ gas (i.e., $66$ USD in June 2023), which is $53\times$ higher than issuing a base transfer transaction. In this work, we introduce the Merkle Pyramid Builder approach, to incrementally build the Merkle tree in an on-chain mixer and update the tree per batch of deposits, which can therefore decrease the overall cost of using the mixer. Our evaluation results highlight the effectiveness of this approach, showcasing a significant reduction of up to $7\times$ in the amortized cost of depositing compared to state-of-the-art on-chain mixers. Importantly, these improvements are achieved without compromising users\u27 privacy. Furthermore, we propose the utilization of verifiable computations to shift the responsibility of Merkle tree updates from on-chain smart contracts to off-chain clients, which can further reduce deposit costs. Additionally, our analysis demonstrates that our designs ensure fairness by distributing Merkle tree update costs among clients over time

Irreversible transformation of ferromagnetic ordered stripe domains in single-shot IR pump - resonant X-ray scattering probe experiments

The evolution of a magnetic domain structure upon excitation by an intense, femtosecond Infra-Red (IR) laser pulse has been investigated using single-shot based time-resolved resonant X-ray scattering at the X-ray Free Electron laser LCLS. A well-ordered stripe domain pattern as present in a thin CoPd alloy film has been used as prototype magnetic domain structure for this study. The fluence of the IR laser pump pulse was sufficient to lead to an almost complete quenching of the magnetization within the ultrafast demagnetization process taking place within the first few hundreds of femtoseconds following the IR laser pump pulse excitation. On longer time scales this excitation gave rise to subsequent irreversible transformations of the magnetic domain structure. Under our specific experimental conditions, it took about 2 nanoseconds before the magnetization started to recover. After about 5 nanoseconds the previously ordered stripe domain structure had evolved into a disordered labyrinth domain structure. Surprisingly, we observe after about 7 nanoseconds the occurrence of a partially ordered stripe domain structure reoriented into a novel direction. It is this domain structure in which the sample's magnetization stabilizes as revealed by scattering patterns recorded long after the initial pump-probe cycle. Using micro-magnetic simulations we can explain this observation based on changes of the magnetic anisotropy going along with heat dissipation in the film.Comment: 16 pages, 6 figure

A Robust Titanium Isophthalate Metal-Organic Framework for Visible-Light Photocatalytic CO2 Methanation

[EN] Isophthalic acid (IPA) has been considered to build metal-organic frameworks (MOFs), owing to its facile availability, unique connection angle-mode, and a wide range of functional groups attached. Constructing titanium-IPA frameworks that possess photoresponse properties is an alluring characteristic with respect to the challenge of synthesizing new titanium-based MOFs (Ti-MOFs) Here, we report the first Ti-IPA MOF (MIP-208) that efficiently combines the use of preformed Ti-8 oxoclusters and in situ acetylation of the 5-NH2-IPA linker. The mixed solid-solution linkers strategy was successfully applied, resulting in a series of multivariate MIP-208 structures with tunable chemical environments and sizable porosity. MIP-208 shows the best result among the pure MOF catalysts for the photocatalytic methanation of carbon dioxide. To improve the photocatalytic performance, ruthenium oxide nanoparticles were photo-deposited on MIP-208, forming a highly active and selective composite catalyst, MIP-208@RuOx, which features a notable visible-light response coupled with excellent stability and recycling ability.S.W. acknowledges the support from the National Natural Science Foundation of China (22071234) and the Fundamental Research Funds for the Central Universities (WK2480000007). S.N. thanks the Ministerio de Ciencia, Innovacion y Universidades (RTI2018-099482-A-I00 project, the Fundacion Ramon Areces (XVIII Concurso Nacional para la Adjudicacion de Ayudas a la Investigacion en Ciencias de la Vida y de la Materia, 2016), and Generalitat Valenciana grupos de investigacion consolidables (AICO/2019/214 project) and Agencia Valenciana de la Innovacion (INNEST/2020/111 project) for financial support. C.-C.C. acknowledges the support from the Program of China Scholarship Council (201700260093) and PHC Cai YuanPei Project (38893VJ). C.M.-C. is grateful for financial support from the Institut Universitaire de France (IUF) and the Paris Ile-de-France Region -DIM "Respore.'' H.G. thanks the Spanish Ministry of Science and Innovation (Severo Ochoa and RTI2018-098237-CO2-1) and Generalitat Valenciana (Prometeo2017/083) for financial support. The authors thank the staff at Synchrotron SOLEIL and the associated scientists for beamtime and assistance during SCXRD data collections on PROXIMA 2A, as well as Dr. Peng Guo and Dr. Nana Yan from Dalian Institute of Chemical Physics (Chinese Academy of Sciences) for the collection of high-resolution PXRD data for Rietveld refinement.Wang, S.; Cabrero-Antonino, M.; Navalón Oltra, S.; Cao, C.; Tissot, A.; Dovgaliuk, I.; Marrot, J.... (2020). A Robust Titanium Isophthalate Metal-Organic Framework for Visible-Light Photocatalytic CO2 Methanation. 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PrimerProspector: de novo design and taxonomic analysis of barcoded polymerase chain reaction primers

Motivation: PCR amplification of DNA is a key preliminary step in many applications of high-throughput sequencing technologies, yet design of novel barcoded primers and taxonomic analysis of novel or existing primers remains a challenging task