Biology subjects

Huck, J.

Publications and source records attributed to Huck, J..

6 recordsLinked to original sources

bioRxiv2026

Coronary artery disease is linked with demyelination and iron deposition in white matter watershed areas

Coronary artery disease increases risk of cognitive decline and stroke and is associated with white matter alterations. However, the biological basis of these changes remains unclear. Myelin content and iron deposition are crucial measures of white matter health and can be measured with quantitative MRI. This study investigated whether myelin and iron alterations occur in coronary artery disease, and their relationship with cognition. In this cross-sectional study, 46 individuals with coronary artery disease and 40 healthy controls aged > 50 years, with normal cognition underwent 3T MRI and cognitive assessments. Quantitative MRI metrics (susceptibility, magnetization transfer saturation, R2* and R1 relaxation rates) were calculated in the border zones between adjacent arterial territories (watershed regions) and in the areas outside these borders (non-watershed regions). Relative to controls, the coronary artery disease group showed lower myelin and higher iron content, as measured by lower magnetization transfer saturation and R1, and higher susceptibility specifically in watershed regions. Importantly, these microstructural alterations were associated with poorer cognitive performance in the coronary artery disease group with lower magnetization transfer and R1related to poorer global cognition and with higher magnetic susceptibility with poorer verbal memory. These findings suggest that coronary artery disease is associated with demyelination and iron deposition in white matter, most prominently in watershed regions, which are known for their susceptibility to stroke. The association of these microstructural alterations with cognition highlights the role of white matter as a key vulnerable region and a promising focus for future mechanistic and therapeutic studies.

neuroscience↗

bioRxiv2025

HKU5 bat merbecoviruses use divergent mechanisms to engage bat and mink ACE2 as entry receptors

Identifying receptors for bat coronaviruses is critical for spillover risk assessment, countermeasure development, and pandemic preparedness. While Middle East respiratory syndrome coronavirus (MERS-CoV) uses DPP4 for entry, the receptors of many MERS-related betacoronaviruses remain unknown. The bat merbecovirus HKU5 was previously shown to have an entry restriction in human cells. Using both pseudotyped and full-length virus, we show that HKU5 uses Pipistrellus abramus bat ACE2 but not human ACE2 or DPP4 as a receptor. Cryo-electron microscopy (cryo-EM) analysis of the virus-receptor complex and structure-guided mutagenesis reveal a spike and ACE2 interaction that is distinct from other ACE2-using coronaviruses. MERS-CoV vaccine sera poorly neutralize HKU5 informing pan-merbecovirus vaccine design. Notably, HKU5 can also engage American mink and stoat ACE2, revealing mustelids as potential intermediate hosts. These findings highlight the versatility of merbecovirus receptor use and underscore the need for continued surveillance of bat and mustelid species.

microbiology↗

bioRxiv2021

Motor Sequences - Separating The Sequence From The Motor. A longitudinal rsfMRI Study

In motor learning, sequence-specificity, i.e. the learning of specific sequential associations, has predominantly been studied using task-based fMRI paradigms. However, offline changes in resting state functional connectivity after sequence-specific motor learning are less well understood. Previous research has established that plastic changes following motor learning can be divided into stages including fast learning, slow learning and retention. A description of how resting state functional connectivity after sequence-specific motor sequence learning (MSL) develops across these stages is missing. This study aimed to identify plastic alterations in whole-brain functional connectivity after learning a complex motor sequence by contrasting an active group who learned a complex sequence with a control group who performed a control task matched for motor execution. Resting state fMRI and behavioural performance were collected in both groups over the course of 5 consecutive training days and at follow-up after 12 days to encompass fast learning, slow learning, overall learning and retention. Between-group interaction analyses showed sequence-specific decreases in functional connectivity during overall learning in the right supplementary motor area (SMA). We found that connectivity changes in key regions of the motor network including the superior parietal cortex (SPC) and primary motor cortex (M1) were not a result of sequence-specific learning but were instead linked to motor execution. Our study confirms the sequence-specific role of SMAthat has previously been identified in online task-based learning studies, and extends it to resting state network changes after sequence-specific MSL.

neuroscience↗

bioRxiv2020

White matter microstructural changes in short-term learning of a continuous visuomotor sequence

Efficient neural transmission is crucial for optimal brain function, yet the plastic potential of white matter (WM) has long been overlooked. Growing evidence now shows that modifications to axons and myelin occur not only as a result of long-term learning, but also after short training periods. Motor sequence learning (MSL), a common paradigm used to study neuroplasticity, occurs in overlapping learning stages and different neural circuits are involved in each stage. However, most studies investigating short-term WM plasticity have used a pre-post design, in which the temporal dynamics of changes across learning stages cannot be assessed. In this study, we used multiple magnetic resonance imaging (MRI) scans at 7 Tesla to investigate changes in WM in a group learning a complex visuomotor sequence (LRN) and in a control group (SMP) performing a simple sequence, for 5 consecutive days. Consistent with behavioral results, where most improvements occurred between the two first days, structural changes in WM were observed only in the early phase of learning (d1-d2), and in overall learning (d1-d5). In LRNs, WM microstructure was altered in the tracts underlying the primary motor and sensorimotor cortices. Moreover, our structural findings in WM were related to changes in functional connectivity, assessed with resting-state functional MRI data in the same cohort, through analyses in regions of interest (ROIs). Significant changes in WM microstructure were found in a ROI underlying the right supplementary motor area. Together, our findings provide evidence for highly dynamic WM plasticity in the sensorimotor network during short-term MSL.

neuroscience↗

bioRxiv2020

Prevalence of Major Limb Loss (MLL) in Post conflict Acholi sub-region of Northern Uganda: Cross sectional study

BACKGROUNDThere is a widely reported preponderance of major limb loss in Northern Uganda, which is believed to have been caused in large part by prolonged civil war. Access to rehabilitation facilities is extremely limited, and there has never been a study to understand how many people have major limb loss, nor how many of them have had access to medical or rehabilitative services. AIMThe first prevalence study of disability and major limb loss in the region, and evaluated spatial patterns of cases of MLL. DESIGNCross-sectional survey. SETTINGThis research was undertaken in a community setting (at subjects homes). POPULATION7,864 randomly selected households throughout the Acholi Sub-Region of Northern Uganda. METHODSThis study comprised two questionnaires, the first to be completed by the head of every sampled household (n=7,864), and the second by any member of the household with major limb loss (n=181). Household locations were examined for spatial autocorrelation using Morans I statistic. The {chi}2 goodness of fit statistic was used to profile those with major limb loss in comparison with the underlying population. RESULTSWe conservatively estimate that there are c.10,117 people with major limb loss in the region who require long-term rehabilitation services (c.0.5% of the population), and c.150,512 people with disabilities other than MLL (c.8.2% of the population). People with major limb loss are spread throughout the region (as opposed to clustered in specific locations) and are disproportionately male, older and less well educated than the general population. CONCLUSIONThis research demonstrates, for the first time, the extent of the inadequacy of long-term rehabilitation services for those with major limb-loss in the study area. We provide new insight into the reasons that people are not accessing medical and rehabilitative services, and propose a way forward through the successful demonstration of an outreach clinic model. CLINICAL REHABILITATION IMPACTThe discovery of the spatial pattern of those with major limb loss, alongside the demonstration of the clinical outreach model, provides a compelling argument for the need of more such services and associated policy frameworks in remote and rural regions in the Global South. TIDIER ChecklistWe confirm that this manuscript conforms to the STROBE Checklist for Cross-Sectional Studies

pathology↗

bioRxiv2018

High resolution atlasing of the venous brain vasculature from 7T quantitative susceptibility

The vascular organization of the human brain can determine neurological and neurophysiological functions, yet thus far it has not been comprehensively mapped. Aging and diseases such as dementia are known to be associated with changes to the vasculature and normative data could help detect these vascular changes in neuroimaging studies. Furthermore, given the well-known impact of venous vessels on the blood oxygen level dependent (BOLD) signal, information about the common location of veins could help detect biases in existing datasets. In this work, a quantitative atlas of the venous vasculature using quantitative susceptibility maps (QSM) acquired with a 0.6 mm isotropic resolution is presented. The Venous Neuroanatomy (VENAT) atlas was created from 5 repeated 7 Tesla MRI measurements in young and healthy volunteers (n = 20, 10 females, mean age = 25.1 {+/-} 2.5 years) using a two-step registration method on 3D segmentations of the venous vasculature. This cerebral vein atlas includes the average vessel location, diameter (mean: 0.84 {+/-} 0.33 mm) and curvature (0.11 {+/-} 0.05 mm-1) from all participants and provides an in vivo measure of the angio-architectonic organization of the human brain and its variability. This atlas can be used as a basis to understand changes in the vasculature during aging and neurodegeneration, as well as vascular and physiological effects in neuroimaging.

neuroscience↗