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Biology subjects

Nikolaeva, D.

Publications and source records attributed to Nikolaeva, D..

3 recordsLinked to original sources

Mannosylated nanoparticle immunogens enhance the circumsporozoite protein-specific B cell response and improve protection against sporozoite challenge

Underprocessed oligomannose glycans on protein nanoparticle immunogens engage the innate immune system through mannose-binding lectin and complement, enhancing immunogen trafficking and B cell responses. However, the extent to which oligomannose glycans directly improve protective immunity has remained unclear. Here we generate a series of CSP-bearing I53-50 nanoparticle malaria vaccine candidates with defined numbers and types of engineered N-linked glycans and systematically evaluate their immunogenicity and protective efficacy. Oligomannose display enhanced early plasmablast and germinal center B cell responses, leading to increased CSP-specific memory B cells, long-lived plasma cells, and durable serum antibody titers. Furthermore, nanoparticles bearing oligomannose glycans conferred the strongest protection against sporozoite challenge. By comparing immunogens with defined glycoforms, we attribute improved immune responses and protection specifically to oligomannose rather than complex or truncated glycans. These results will help guide the development of general strategies for glycan engineering aimed at enhancing the protective efficacy of nanoparticle vaccines.

immunology↗

Wiring together large single-cell RNA-seq sample collections

Single-cell RNA-seq methods are being increasingly applied in complex study designs, which involve measurements of many samples, commonly spanning multiple individuals, conditions, or tissue compartments. Joint analysis of such extensive, and often heterogeneous, sample collections requires a way of identifying and tracking recurrent cell subpopulations across the entire collection. Here we describe a flexible approach, called Conos (Clustering On Network Of Samples), that relies on multiple plausible inter-sample mappings to construct a global graph connecting all measured cells. The graph can then be used to propagate information between samples and to identify cell communities that show consistent grouping across broad subsets of the collected samples. Conos results enable investigators to balance between resolution and breadth of the detected subpopulations. In this way, it is possible to focus on the fine-grained clusters appearing within more similar subsets of samples, or analyze coarser clusters spanning broader sets of samples in the collection. Such multi-resolution joint clustering provides an important basis for downstream analysis and interpretation of sizeable multi-sample single-cell studies and atlas-scale collections.

bioinformatics↗

Relationships between clans and genetic kin explain cultural similarities over vast distances: the case of Yakutia

Archaeological studies sample ancient human populations one site at a time, often limited to a fraction of the regions and periods occupied by a given group. While this bias is known and discussed in the literature, few model populations span areas as large and unforgiving as the Yakuts of Eastern Siberia. We systematically surveyed 31,000 square kilometres in the Sakha Republic (Yakutia) and completed the archaeological study of 174 frozen graves, assembled between the 15th and the 19th century. We analysed genetic data (autosomal genotypes, Y-chromosome haplotypes and mitochondrial haplotypes) for all ancient subjects and confronted these to data on 190 modern subjects from the same area and the same population. Ancient familial links were identified between graves up to 1500 km apart, as well as paternal clans. We provide new insights on the origins of the contemporary Yakut population and demonstrate that cultural similarities in the past were linked to (i) the expansion of specific paternal clans, (ii) preferential marriage among the elites and (iii) funeral choices that could constitute a bias in any ancient population study.

genetics↗