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Biology subjects

Hjorth, M.

Publications and source records attributed to Hjorth, M..

4 recordsLinked to original sources

Migrations facilitated the cultural diffusion of megaliths in Neolithic Europe

Around 6700 BP (years before present), Neolithic Europe saw the emergence of megalithic monuments in northern France, followed by a rapid spread to the rest of the continent1. However, whether this was driven by the transmission of ideas (cultural diffusion) or the movement of people remains debated. To test whether this spread coincided with population movements, we reconstructed the population history of the European Neolithic ([~]6500-4800 BP) by analysing genomic data from 2963 ancient individuals, including 46 unpublished genomes from megalithic and related contexts. To assess the alternative scenario whereby megaliths spread through contact networks, as expected under cultural diffusion, we integrated archaeological evidence with radiocarbon chronologies to reconstruct past trading networks. We identify northern France, where megaliths first emerged, as a zone of genetic admixture and cultural influence from the two major early Neolithic divisions: the Cardial of the Western Mediterranean and the Linear Pottery traditions of central Europe. From this admixed population, we uncover several migrations associated with the formation of the Funnel Beaker Culture in north-central Europe and the neolithisation of Scandinavia and the British Isles. We find that megaliths were spread exclusively within regions impacted by Cardial-related genetic ancestry, but only in the British Isles and Ireland did their emergence coincide with the time of the migration. The temporal delay between the migrations and the spread of megaliths elsewhere reveals that neither population movements nor cultural diffusion alone fully explains the geospatial distribution of the megalithic tradition. Rather, megaliths diffused across different Neolithic groups whose long-distance trade networks formed in the wake of earlier population movements. Our findings highlight the need to move beyond simplistic interpretations that present migrations or cultural diffusion as isolated events bringing technological and cultural innovations.

evolutionary biology↗

Long-term T cell perturbations and waning antibody levels in individuals needing hospitalization for COVID-19

COVID-19 is being extensively studied, and much remains unknown regarding the long-term consequences of the disease on immune cells. The different arms of the immune system are interlinked, with humoral responses and the production of high-affinity antibodies being largely dependent on T cell immunity. Here, we longitudinally explored the effect COVID-19 has on T cell populations and the virus-specific T cells, as well as neutralizing antibody responses, for 6-7 months following hospitalization. The CD8+ TEMRA and exhausted CD57+CD8+ T cells were markedly affected with elevated levels that lasted long into convalescence. Further, markers associated with T-cell activation were upregulated at the inclusion, and in the case of CD69+CD4+ T cells this lasted all through the study duration. The levels of T cells expressing negative immune checkpoint molecules were increased in COVID-19 patients and sustained for a prolonged duration following recovery. Within 2-3 weeks after symptom onset, all COVID-19 patients developed anti-nucleocapsid IgG and spike-neutralizing IgG as well as SARS-CoV-2-specific T cell responses. In addition, we found alterations in follicular T helper (TFH) cell populations, such as enhanced TFH-TH2 following recovery from COVID-19. Our study revealed significant and long-term alterations in T cell populations and key events associated with COVID-19 pathogenesis.

immunology↗

Mucin hydrogel glyco-modulation to investigate immune activity of mucin glycans

Mucins are multifunctional glycosylated proteins that are increasingly investigated as building blocks of novel biomaterials. Once assembled into hydrogels (Muc gels), mucins were shown to modulate the recruitment and activation of immune cells and avoid fibrous encapsulation in vivo. However, nothing is known about the early immune response to Muc gels. This study characterizes the response of macrophages, important orchestrators of the material-mediated immune response, over the first 7 days in contact with Muc gels. The role of mucin-bound sialic acid sugar residues was investigated by first enzymatically cleaving the sugar, then assembling the mucin variants into covalently crosslinked hydrogels with rheological and surface nanomechanical properties similar to non-modified Muc gels. Results with THP1 and human primary peripheral blood monocytes-derived macrophages were strikingly consistent and showed that Muc gels transiently activate the expression of both pro-inflammatory and anti-inflammatory cytokines and cell surface markers, with a maximum on the first day and loss of the effect after 7 days. The activation was sialic acid-dependent for a majority of the markers followed. The pattern of gene expression, protein expression, and functional measurements did not strictly correspond to M1 or M2 macrophage phenotypes. This study highlights the complex early events in macrophage activation in contact with mucin materials and the importance of sialic acid residues in such a response. The enzymatic glyco-modulation of Muc gels appears as a useful tool to help understand the biological functions of specific glycans on mucins which can further inform on their use in various biomedical applications.

bioengineering↗

Immune-informed mucin hydrogels evade fibrotic foreign body response in vivo

The immune-mediated foreign body response to biomaterial implants can trigger the formation of insulating fibrotic capsules that can compromise implant function. To address this challenge, we leverage the intrinsic bioactivity of the mucin biopolymer, a heavily glycosylated protein that forms the protective mucus gel covering mucosal epithelia. By using a bioorthogonal inverse electron demand Diels-Alder reaction, we crosslink mucins into implantable hydrogels. We show that mucin hydrogels (Muc-gels) modulate the immune response driving biomaterial-induced fibrosis. Muc-gels did not elicit fibrosis 21 days after implantation in the peritoneal cavity of C57Bl/6 mice, whereas medical-grade alginate hydrogels (Alg-gels) were covered by fibrous tissues. Further, Muc-gels dampened the recruitment of innate and adaptive immune cells to the gel and triggered a pattern of very mild activation marked by a noticeably low expression of the fibrosis-stimulating TGF-{beta}1 cytokine. With this advance in mucin materials, we provide an essential tool to better understand mucin bioactivities and to initiate the development of new mucin-based and mucin-inspired immune-informed materials for implantable devices subject to fibrotic encapsulation.

bioengineering↗