Biology subjects

Held, S.

Publications and source records attributed to Held, S..

4 recordsLinked to original sources

bioRxiv2025

Dynamin regulates PLK-1 localization and spindle pole assembly during mitosis

Accurate mitosis is essential for genome stability. Although dynamin is best known for its role in vesicular trafficking, its functions during mitosis remain unclear. Here, we identify a mitotic role for the C. elegans dynamin homolog DYN-1 in regulating spindle assembly and the localization of the key mitotic regulators SPD-2 and PLK-1. Depletion of DYN-1 results in enlarged metaphase spindle poles and increased centrosomal SPD-2 and PLK-1 levels. These effects likely depend on DYN-1-mediated vesicular trafficking, as shown by assays with the dyn-1(ky51) allele. Additionally, a subset of DYN-1-depleted embryos exhibit altered PLK-1 localization at the midbody during late mitosis, correlating with midbody assembly defects. Together, these findings establish DYN-1 as a previously unrecognized regulator of spindle pole organization and early midbody assembly. SIGNIFICANCE STATEMENTDynamin is primarily known for its function in endocytosis, but its involvement in mitosis is not well defined. This study shows that dynamin helps organize mitotic spindle poles, ensures proper centrosome localization of SPD-2 and PLK-1, and supports early steps of midbody assembly in C. elegans embryos. These findings reveal a previously unrecognized mitotic role for dynamin and suggest new links between membrane dynamics, spindle organization, and the cytokinetic machinery.

cell biology↗

bioRxiv2024

Generation of antigen-specific paired heavy-light chain antibody sequences using large language models

The traditional process of antibody discovery is limited by inefficiency, high costs, and low success rates. Recent approaches employing artificial intelligence (AI) have been developed to optimize existing antibodies and generate antibody sequences in a target-agnostic manner. In this work, we present MAGE (Monoclonal Antibody GEnerator), a sequence-based Protein Language Model (PLM) fine-tuned for the task of generating paired human variable heavy and light chain antibody sequences against targets of interest. We show that MAGE can generate novel and diverse antibody sequences with experimentally validated binding specificity against SARS-CoV-2, an emerging avian influenza H5N1, and respiratory syncytial virus A (RSV-A). MAGE represents a first-in-class model capable of designing human antibodies against multiple targets with no starting template.

bioinformatics↗

bioRxiv2024

Neutralisation sensitivity of the SARS-CoV-2 BA.2.87.1 variant

Against the backdrop of the rapid global takeover and dominance of BA.1/BA.2 and subsequently BA.2.86 lineages, the emergence of a highly divergent SARS-CoV-2 variant warrants characterization and close monitoring. Recently, another such BA.2 descendent, designated BA.2.87.1, was detected in South Africa. Here, we show using spike-pseudotyped viruses that BA.2.87.1 is less resistant to neutralisation by prevailing antibody responses in Sweden than other currently circulating variants such as JN.1. Further we show that a monovalent XBB.1.5-adapted booster enhanced neutralising antibody titers to BA.2.87.1 by almost 4-fold. While BA.2.87.1 may not outcompete other currently-circulating lineages, the repeated emergence and transmission of highly diverged variants suggests that another large antigenic shift, similar to the replacement by Omicron, may be likely in the future.

immunology↗

bioRxiv2021

Subclinical Mastitis in Dairy Cows is Associated with Changes in Salivary Serum Amylase-A, Social Behavior and Activity Profiles

The aim of this study was to identify detailed changes in behavior, and in salivary serum amyloid A (SAA), associated with subclinical mastitis. This included standard sickness behaviors (which form part of an adaptive response to conserve energy, minimize heat loss and facilitate recovery following infection and inflammation) and lesser-studied behaviors, that are biologically predicted to change at low-level infection, and therefore particularly relevant for detecting subclinical mastitis (here labelled luxury behaviors). SAA is a physiological marker of systemic inflammation, with levels in milk and serum already known to increase during subclinical mastitis. We investigated whether the same was true for SAA in cow saliva. Data were collected for n = 34 commercial barn-housed dairy cows, tested in 17 matched-pairs. Each pair comprised a cow with subclinical mastitis (SCM) and a healthy control (CTRL), identified using somatic cell count (SCC) (SCM: SCC >200 x1000 cells/ml; CTRL: SCC <100 x1000 cells/ml). SCM cows were selected for study ad-hoc, at which point they were paired with a CTRL cow, based upon parity and calving date; consequently, the full data set was accrued over several months. Data were collected for each pair over 3 days: SCC (l4:00-l5:00h) Day 1; behavior (24h from 00:00h) Day 2; salivary serum amyloid-A (SAA) Day 3. We report, for the first time, that an increase in salivary SAA occurs during subclinical mastitis; SAA was higher in SCM cows and demonstrated a positive (weak) correlation with SCC. The behavioral comparisons revealed that SCM cows had reductions in activity (behavioral transitions and distance moved), social exploration, social reactivity (here: likelihood to move away/be displaced following receipt of agonism), performance of social grooming and head butts, and the receipt of agonistic non-contact challenges. In addition, SCM cows received more head swipes, and spent a greater proportion of time lying with their head on their flank than CTRL cows. SCM cows also displayed an altered feeding pattern; they spent a greater proportion of feeding time in direct contact with two conspecifics, and a lower proportion of feeding time at self-locking feed barriers, than CTRL cows. Behavioral measures were found to correlate, albeit loosely, with serum SAA in a direction consistent with predictions for sickness behavior. These included positive correlations with both lying duration and the receipt of all agonistic behavior, and negative correlations with feeding, drinking, the performance of all social and all agonistic behavior, and social reactivity. We conclude that changes in salivary SAA, social behavior, and activity offer potential in the detection of subclinical mastitis and recommend further investigation to substantiate and refine our findings.

zoology↗