Biology subjects

Wright, D. K.

Publications and source records attributed to Wright, D. K..

6 recordsLinked to original sources

bioRxiv2026

Anatomical determinants of DTI-ALPS: effects of ROI definition, ventricular morphology, and periventricular deformation

The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index is increasingly used as a non-invasive MRI biomarker of glymphatic and perivascular function, yet the anatomical validity and measurement stability of the metric remain incompletely characterised. Using diffusion MRI data from 850 healthy young adults and 150 healthy ageing participants from the Human Connectome Project, I systematically evaluated the influence of region-of-interest (ROI) placement and ventricular anatomy on ALPS measurements. Reference ALPS implementations demonstrated substantial hemispheric variability, with a median left-right difference of 12.5% and marked asymmetry in the underlying numerator and denominator tensor components. A two-stage optimisation framework incorporating fibre-pool alignment, hemispheric symmetry, component stability, and directional purity identified anatomically improved ROI configurations that significantly increased fibre specificity and reduced measurement variability in independent validation cohorts. Despite these improvements, residual hemispheric asymmetry persisted, suggesting an intrinsic anatomical contribution to ALPS variability. In the healthy ageing cohort, ventricular volume emerged as the strongest predictor of ALPS, explaining substantially more variance than chronological age. Voxel-wise deformation-based morphometry demonstrated that lower ALPS values were associated with ventricular and periventricular expansion, while optimisation increased coupling between ALPS and ventricular anatomy. Collectively, these findings indicate that ALPS measurements are strongly influenced by ROI definition, ventricular morphology, and surrounding periventricular tissue architecture. Rather than functioning as a direct measure of glymphatic transport in isolation, ALPS appears to represent a composite anatomical diffusion biomarker shaped by both methodological implementation and underlying neuroanatomy. These results provide a framework for improving methodological standardisation and interpretation of ALPS measurements in future neuroimaging studies.

neuroscience↗

bioRxiv2025

Stable isotopes of soil provide insights into hominin paleoenvironments in the Khovaling Loess Plateau of Southern Tajikistan, Central Asia

This study presents a multi-proxy investigation of loess-paleosol sequences from the Khovaling Loess Plateau (KLP) in southern Tajikistan to explore long-term human-environment interactions during the Early Paleolithic. This region has been the focus of numerous archaeological projects since Soviet times, as it contains evidence of some of the oldest ([~]0.9 Ma) hominin occupations in Central Asia and is one of the key regions connecting eastern Asia to centers of hominin evolution that lie to the west. Previous archaeological expeditions have discovered rich collections of stone tools from alternating non-pedogenically modified loess and paleosol sequences at the archaeological sites of Karatau, Lakhuti, Obi-Mazar, and Kuldura. We analyzed lipid biomarkers such as n-alkanes, polycyclic aromatic hydrocarbons (PAHs), together with newly generated stable isotopes ({delta}{superscript 1}3C, {delta}{superscript 1}N), magnetic susceptibility, and archaeological assemblages from three sites: Obi-Mazar/Lakhuti (on-site), and non-artifact-bearing strata from Kuldara (near-site) and Khonako-II (off-site), focusing on pedocomplexes (PCs) 4, 5, and 6 and their intercalated loess layers. High odd-over-even predominance (OEP) and average chain lengths (ACL) suggest that soil organic matter is predominantly derived from higher-order terrestrial plants, with better preservation in paleosols compared to loess layers. The inverse correlations of {delta}{superscript 1}3C with TOC and C/N reflect organic matter degradation, while elevated {delta}{superscript 1}N in paleosols suggests enhanced nitrogen cycling under warmer and drier conditions. Magnetic susceptibility and {delta}{superscript 1}3C trends reveal a progressive shift toward open grassland ecosystems since [~]0.8 Ma, with intensified pedogenesis during interglacial stages MIS 11, 13, and 15. The spatial distribution of PAH concentrations and lithic artifact densities further highlights human-environment interactions in the KLP locality. Obi-Mazar exhibits abundant lithic materials and high PAH levels, indicating repeated occupation and frequent burning in a resource-rich riverine setting. Kuldara exhibits moderate PAHs but minimal artifacts, whereas Khonako-II records only a minimal level of signals, reflecting a decrease in human impact with distance from the water source. Together, these findings demonstrate that Early Paleolithic hominins preferentially occupied ecologically stable, pedogenically developed zones during interglacial phases, contributing to localized fire regimes and shaping their landscapes. This study provides a refined paleoenvironmental framework for understanding hominin adaptations in Central Asia during the Pleistocene.

ecology↗

bioRxiv2025

Stone Age anthropogenic impacts to forest development in the interior Scandinavian Peninsula

Forest growth and development is a highly studied phenomenon in which humans have proven to be influential in shaping structure and composition. Delineating the long-term processes of human-environment interactions is crucial for understanding the history and trajectory of landscape formation and vegetation development. Yet, extensive knowledge of the ecological impacts of Stone Age anthropogenic activity is still lacking, particularly from Fennoscandian sites. A sediment core from South Mesna lake from the interior Scandinavian Peninsula was extracted to investigate the long-term evolutionary effects of human-environment interactions following deglaciation (c. 10,500 cal. BP) and initial colonization of the region. Analysis of the core involved microscopic/trace analytical methods, including geochemical analysis, stable isotope analysis, fecal biomarker analysis, and pollen analysis. The combined evidence demonstrates that anthropogenic impacts are prominent shapers of the ecological trajectory and landscape development of the region since the Early Neolithic (c. 5900 cal. BP), which has left a footprint on modern-day land cover. SignificanceAnthropogenic impacts on the environment have been observed to have had notable consequences on global and regional ecological trajectories and environmental development. Yet, how coupled human-environment interactions affect the long-term ecological complexion of boreal landscapes, such as those of the interior Scandinavian Peninsula, is not widely studied. This article presents evidence of early anthropogenic impacts to a forests ecology during the Holocene. Fecal biomarker and pollen analyses make it possible to provide micro-archaeological evidence of human activity and correlate it with noteworthy changes in forest structure. Our data points to a specific co-evolutionary forest development trajectory which is connected to millennial-scale human settlement patterns.

ecology↗

bioRxiv2024

Evidence for reduced choroid plexus volume in the aged brain

BackgroundThe choroid plexus plays an important role in brain homeostasis, including the active secretion of cerebrospinal fluid. Its function and structure have been reported to be affected by normal ageing. However, existing measures of choroid plexus volume may be complicated by partial volume (in vivo MRI) and tissue fixation artefacts (histology). In this study, we investigate possible changes in choroid plexus volume within the lateral ventricles of aged mice utilising two structural MRI protocols explicitly designed for time-efficient, high-resolution in vivo imaging of the choroid plexus. MethodsTwo MRI sequences were utilised to examine in vivo choroid plexus volume in the lateral ventricles of young ([~]6 months) and aged ([~]24 months) mouse brains: 1) an ultra-long echo-time T2 weighted fast-spin-echo and 2) a multi-TE T2* mapping protocol. A test-retest study was performed on a subset of the data to examine the reproducibility of choroid plexus volume estimation. A two-way ANOVA test was performed to determine possible differences in choroid plexus volume in young and aged mouse groups across the two distinct MRI protocols. ResultsReproducibility tests showed a low test-retest variability of the manual segmentation pipeline for both MRI protocols. A statistically significant reduction of in vivo choroid plexus volume was found in the aged mouse brain. This finding is concordant with previous histology studies that have observed a reduction in epithelial cell height with ageing across a wide range of species. ConclusionsWe present an in vivo investigation of changes to lateral ventricle choroid plexus volume in the mouse brain utilising a manual segmentation approach based on two bespoke MRI protocols designed for time-efficient high resolution imaging of the choroid plexus. Furthermore, based on these protocols, we provide evidence for a reduction in choroid plexus volume in the aged brain. This research provides insight for studies utilising MRI measurements of choroid plexus volume as a biomarker of age-related neurologic conditions as it indicates that the ageing process itself does not result in hypertrophy of the choroid plexus, but a decrease in tissue volume.

neuroscience↗

bioRxiv2023

Development of endothelial-targeted CD39 as a therapy for ischaemic stroke

BackgroundIschaemic stroke is characterized by a necrotic lesion in the brain surrounded by an area of dying cells termed the penumbra. Salvaging the penumbra either with thrombolysis or mechanical retrieval is the cornerstone of stroke management. At-risk neuronal cells release extracellular adenosine triphosphate (eATP) triggering microglial activation and causing a thromboinflammatory response culminating in endothelial activation and vascular disruption. This is further aggravated by ischaemia-reperfusion (I/R) injury that follows all reperfusion therapies. The ecto-enzyme CD39 regulates eATP by hydrolysing to adenosine which has anti-thrombotic and anti-inflammatory properties and reverses I/R injury. MethodsWe developed anti-VCAM-CD39 that targets the antithrombotic and anti-inflammatory properties of recombinant CD39 to the activated endothelium of the penumbra by binding to vascular cell adhesion molecule (VCAM)-1. Mice were subjected to 30 minutes of middle cerebral artery occlusion (MCAo) and analysed at 24h. Anti-VCAM-CD39 or control agents (saline, non-targeted CD39, or anti-VCAM-inactive CD39) were given at 3h post-MCAo. ResultsAnti-VCAM-CD39 treatment reduced neurological deficit; MRI confirmed significantly smaller infarcts together with an increase in cerebrovascular perfusion. Anti-VCAM-CD39 also restored blood brain barrier (BBB) integrity and reduced microglial activation. Coadministration of anti-VCAM-CD39 with thrombolytics (tPA) further reduced infarct volumes and attenuated BBB permeability with no associated increase in intracranial haemorrhage. ConclusionAnti-VCAM-CD39, uniquely targeted to endothelial cells, could be a new stroke therapy even when administered 3 h post ischaemia and may further synergise with thrombolytic therapy to improve stroke outcomes.

neuroscience↗

bioRxiv2018

Elimination of vesicular zinc alters the behavioural and neuroanatomical effects of social defeat stress in mice

Chronic stress can have deleterious effects on mental health, increasing the risk of developing depression or anxiety. But not all individuals are equally affected by stress; some are susceptible while others are more resilient. Understanding the mechanisms that lead to these differing outcomes has been a focus of considerable research. One unexplored mechanism is vesicular zinc - zinc that is released by neurons as a neuromodulator. We examined how chronic stress, induced by repeated social defeat, affects mice that lack vesicular zinc due to genetic deletion of zinc transporter 3 (ZnT3). These mice, unlike wild type mice, did not become socially avoidant of a novel conspecific, suggesting resilience to stress. However, they showed enhanced sensitivity to the potentiating effect of stress on cued fear memory. Thus, the contribution of vesicular zinc to stress susceptibility is not straightforward. Stress also increased anxiety-like behaviour but produced no deficits in a spatial Y-maze test. We found no evidence that microglial activation or hippocampal neurogenesis accounted for the differences in behavioural outcome. Volumetric analysis revealed that ZnT3 KO mice have larger corpus callosum and parietal cortex volumes, and that corpus callosum volume was decreased by stress in ZnT3 KO, but not wild type, mice.

neuroscience↗