Biology subjects

Herbert, R.

Publications and source records attributed to Herbert, R..

7 recordsLinked to original sources

bioRxiv2026

BeatRatePy - Automated Hight-Throughput Python-Based Beat Rate Quantification and Generation of Speed and Contraction Traces

Analysing cardiac motion from label free imaging can be difficult, especially when recordings vary in quality or show complex movement. We developed a Python-based pipeline that automatically measures beat rate, contraction, speed from transmitted light timelapse data. The workflow runs in a Jupyter notebook and uses straightforward steps that can be followed easily, making the analysis accessible including to users with limited coding experience. Using human iPSC-derived cardiomyocytes imaged on a Zeiss Cell Discoverer 7, the pipeline produced beat rates, contraction and contraction speed measurements that matched expected behaviour. To test wider use, we applied the same workflow to killifish larvae heart recordings and public datasets, changing only basic input parameters. The pipeline performed consistently across these different systems and did not require changes to the underlying code. By supporting clear parameter control and use across laboratories, microscopy platforms and repositories, this approach strengthens reproducible analysis of cardiac motion from label free imaging.

cell biology↗

bioRxiv2026

A humanized Aβ mouse model reveals E4-dependent cognitive impairments, microglial activation, and cerebrovascular dysfunction

Apolipoprotein E4 (E4) increases the risk of Alzheimers disease (AD) by up to 12-fold. However, understanding of the mechanisms underlying this increased risk has been limited by a lack of preclinical models that accurately reflect the effects of E4 in the presence of humanized non-mutant amyloid-{beta} precursor protein (hA{beta}PP). Therefore, we studied novel humanized APOE and hA{beta}PP mice to investigate the contributions of the E4 genotype to cognitive, inflammatory, and vascular dysfunction, specifically comparing male and female E3/hA{beta}PP and E4/hA{beta}PP mice. E4/hA{beta}PP mice exhibited impaired nest-building behavior and novel object recognition compared with E3/hA{beta}PP mice. Microglial content was higher in E4/hA{beta}PP mice, whereas astrocyte content was not different across groups. E4/hA{beta}PP mice had greater carotid and cerebral artery stiffness, and higher collagen I content in cerebral arteries than E3/hA{beta}PP mice. Under static pressure, cerebral artery endothelium-dependent and endothelium-independent vasodilation were similar across genotypes. However, high pulse pressure selectively impaired cerebral artery endothelial function in E4/hA{beta}PP mice, with the greatest impairment observed in females. The E4/hA{beta}PP mice also exhibited higher cortical expression of Nox2 and Sod1 and elevated cerebral artery Il1b expression. As such, E4/hA{beta}PP mice exhibit convergent cognitive, inflammatory, and vascular abnormalities that recapitulate several features of AD. Elevated pulse pressure revealed an E4-dependent vulnerability of the cerebral vasculature, suggesting that vascular stress may be an important contributor to disease risk. Together, our findings support the use of the APOExhA{beta}PP model to investigate the mechanisms by which E4 promotes vascular dysfunction, neuroinflammation, and cognitive impairment in AD.

physiology↗

bioRxiv2026

Immunization With Herpes Simplex Virus Nanoparticles Targeting Both Attachment and Fusion Protect Against Infection

Herpes simplex virus 2 (HSV-2) is associated with genital ulcers, neonatal encephalitis, increased risk of HIV infection, and dementia. There is no licensed HSV-2 vaccine. We developed nanoparticles displaying the HSV-2 attachment protein gD and fusion mediation protein complex gH/gL. Immunization of mice and non-human primates elicited high levels of neutralizing antibodies. Vaccination conferred robust protection in mice, preventing disease and nearly eliminating infection and shedding following HSV-2 challenge. While gD induced high neutralizing antibody titers, gH/gL contributed substantially to protection despite lower neutralization titers. Instead, gH/gL immunization generated strong fusion-blocking responses which were an important correlate of protection, showing that standard neutralization assays incompletely capture the importance of fusion-blocking activity. These findings demonstrate that targeting both HSV-2 attachment and fusion elicit complementary mechanisms for protection from infection and that neutralizing antibody alone may be insufficient for protection. Overall, these results present an innovative strategy for an HSV-2 vaccine.

immunology↗

bioRxiv2025

Physical disturbance induces heart stop in mangrove killifish, Kryptolebias marmoratus embryos

The mangrove killifish, Kryptolebias marmoratus, is a highly unique vertebrate species, known for its unusual sexual systems. It is one of two known self-fertilizing simultaneous hermaphroditic vertebrates, alongside the related Kryptolebias ocellatus1,2. While individuals can be born as primary males, most are born as hermaphrodites3 and some turn into secondary males later in life4. K. marmoratus is exceptionally tolerant of harsh and variable environmental conditions. This includes emersion as well as widely ranging salinities and temperatures5-7. Embryos can enter diapause, a state of arrested development, when conditions are unfavourable8,9.

developmental biology↗

bioRxiv2024

Single-Cell Temporal Atlas of Myeloid Cells in the Live Haemorrhagic Brain

Innate immune cells contribute to both secondary brain injury and repair following intracerebral hemorrhage (ICH). However, the specific signaling pathways that govern initial inflammatory and subsequent reparative myeloid programs in living patients remain poorly understood. To better characterize mononuclear phagocyte cell changes over time, we generated a single-cell transcriptomic dataset of paired hematoma clot evacuates and peripheral blood samples from 10 patients following ICH (5 - 290 hours). We identified distinct populations of activated and TNF-low microglia, as well as a unique, highly activated population of CD14+ monocytes in the hematoma. Perturbation analysis identified TNF signaling as the primary driver of hematoma monocyte activation. Custom temporal trajectory analysis using single-cell foundation model embeddings found that this TNF response in monocytes was transient, peaking early after hemorrhage and decreasing over the following 48 hours as monocytes shifted to reparative transcriptional programs. Transiently activated microglia emerged as the likely acute source of TNF, signaling through monocyte TNFR2. Surprisingly, acute TNF signaling in CD14+ monocytes was also associated with better severity-adjusted neurological outcomes both in our cohort and an independent validation cohort. These findings suggest acute TNF signaling between activated microglia and hematoma-associated monocytes, particularly through TNFR2, may contribute to recovery following ICH. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/630187v2_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@ff4fa0org.highwire.dtl.DTLVardef@1c4cc5borg.highwire.dtl.DTLVardef@1449761org.highwire.dtl.DTLVardef@2e7ea6_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2023

Spatial and temporal changes in microbial communities and greenhouse gas emissions in a denitrifying woodchip bioreactor at low water temperatures

Nitrogen (N) pollution is a major threat to ecosystems and a driver of climate change through emissions of the greenhouse gas nitrous oxide (N2O). Mining activities are increasingly recognized for contributing to N pollution due to undetonated, N-based explosives. A woodchip denitrifying bioreactor, installed to treat nitrate-rich leachate from waste rock dumps in northern Sweden, was monitored for two years to determine the spatial and temporal distribution of microbial communities in pore water and woodchips and their genetic potential for different N transformation processes, and how this affected the N removal capacity and possible production of undesired N species, like ammonium, nitrite and N2O. About 80 and 65 % of the nitrate was removed from the leachate the first and second operational year, respectively, which agreed with a decrease in dissolved organic carbon in the outlet water. There was a succession in the microbial community over time and in space along the reactor length in both pore water and woodchips, which was reflected in the genetic potential for N cycling and ultimately also reactor performance. We conclude that DNRA had minimal impact on the overall N removal efficiency due to the low relative abundance of the key gene nrfA involved in DNRA and the low production of ammonium. However, nitrite, ammonium, and N2O were formed in the bioreactor and released in the effluent water, although direct emissions of N2O from the surface was low. The N2O production in the reactor might be explained by the ratio between the genetic potential for overall denitrification and N2O reduction in the woodchip and pore water communities, as indicated by the low ratio between the abundance of nir and nosZ genes. Altogether, the results indicate that the denitrification pathway was temporally as well as spatially separated along the reactor length, and that unwanted reactive N species were produced at different time points and locations in the reactor. Thus, the succession of microbial communities in woodchip denitrifying bioreactors treating mining impacted water develops slowly at low temperature, which impacts the reactor performance.

ecology↗

bioRxiv2022

Intranasal pediatric parainfluenza virus-vectored SARS-CoV-2 vaccine candidate is protective in macaques

Pediatric SARS-CoV-2 vaccines are needed that elicit immunity directly in the airways, as well as systemically. Building on pediatric parainfluenza virus vaccines in clinical development, we generated a live-attenuated parainfluenza virus-vectored vaccine candidate expressing SARS-CoV-2 prefusion-stabilized spike (S) protein (B/HPIV3/S-6P) and evaluated its immunogenicity and protective efficacy in rhesus macaques. A single intranasal/intratracheal dose of B/HPIV3/S-6P induced strong S-specific airway mucosal IgA and IgG responses. High levels of S-specific antibodies were also induced in serum, which efficiently neutralized SARS-CoV-2 variants of concern. Furthermore, B/HPIV3/S-6P induced robust systemic and pulmonary S-specific CD4+ and CD8+ T-cell responses, including tissue-resident memory cells in lungs. Following challenge, SARS-CoV-2 replication was undetectable in airways and lung tissues of immunized macaques. B/HPIV3/S-6P will be evaluated clinically as pediatric intranasal SARS-CoV-2/parainfluenza virus type 3 vaccine. One-Sentence SummaryIntranasal parainfluenza virus-vectored COVID-19 vaccine induces anti-S antibodies, T-cell memory and protection in macaques.

immunology↗