Biology subjects

West, D.

Publications and source records attributed to West, D..

5 recordsLinked to original sources

bioRxiv2026

Stepping-stone population structure and sidespread clonality of the mesophotic octocoral Swiftia exserta in the warm temperate northwest Atlantic

Isolated mesophotic banks form spatially discrete networks of patchy ecosystems along continental shelves. Their long-term persistence depends on connectivity among populations of the dominant coral species that structure these communities. Yet the scale of larval-mediated gene flow across these networks remains poorly characterized. Similarly, the extent to which clonal propagation shapes local population dynamics is unresolved, leaving the relative contributions of sexual and asexual reproduction to population maintenance an open question. Here, population genomics and high-resolution (1km) biophysical larval dispersal modeling are integrated to resolve the genetic connectivity and clonal dynamics of Swiftia exserta, a key habitat-forming octocoral, across 13 mesophotic banks spanning the U.S. Gulf and eastern coast within the Warm Temperate Northwest Atlantic (WTNWA) coastal and shelf biogeographic province. Genome-wide SNP markers derived from Restriction-site Associated Sequencing (RADseq) were genotyped across 288 individuals. About 40% of individuals belonged to clonal genets confined to single banks within meters of one another, indicating that asexual propagation sustains local density but plays no detectable role in inter-bank connectivity. Population genetic analyses pointed to isolation by distance as the primary structuring force, with the majority of molecular variance residing within rather than among populations. The west-most population, East Flower Garden Banks, was the most differentiated population in the WTNWA Northern Gulf ecoregion, reflecting its peripheral position within the bank network. The Edisto population from the WTNWA Carolinian ecoregion, was distinct from all others, implicating the Florida Peninsula as a phylogeographic barrier. Biophysical particle-tracking simulations independently recovered the same spatial structure, with modeled larval exchange consistent with the genomic signal across the bank network. These findings reveal that S. exserta persists across the northern WTNWA province through a dual reproductive strategy of clonality at the bank scale and episodic larval exchange at the network scale, with implications for the conservation and management of mesophotic octocoral metacommunities.

ecology↗

bioRxiv2026

In Vivo 4D Oxy-Wavelet MRI as a Non-Invasive Biomarker of Brain Mitochondrial Function across the Lifespan

Mitochondria are essential for cellular energy production and are particularly critical for brain development and function. Neurons rely predominantly on oxidative phosphorylation for energy production, rendering the brain highly vulnerable to mitochondrial dysfunction. Consequently, impaired mitochondrial function contributes to a broad spectrum of neurological and systemic disorders, making mitochondria attractive therapeutic targets. Despite this importance, there is currently no non-invasive, spatially resolved method to assess mitochondrial function in the intact living brain. Here, we establish a non-invasive functional MRI approach--4D Oxy-wavelet MRI--to probe in vivo mitochondrial electron transport chain (ETC) function in a spatially specific manner across the lifespan, from fetal to adult brains. This method employs a low-rank k-t sub-Nyquist acquisition strategy to achieve simultaneous structural and functional imaging with high spatial (78 m) and temporal ([~]14 ms) resolution, enabling motion-robust imaging in multi-fetal mouse pregnancies. Mitochondrial ETC function is interrogated by measuring oxygen homeostasis responses to brief hypoxic challenges, analyzed using computational time-frequency wavelet profiling. We validate this approach in mouse models of mitochondrial respiratory chain disease and late-onset Alzheimers disease, from in utero fetuses to adults, and demonstrate reproducibility and specificity using pharmacological hyperemia and ETC complex I inhibition. We further show parallel wavelet responses in placenta and fetal brain, enabling multi-organ interrogation of the placenta-brain axis. Finally, we present first-in-human feasibility data, supporting translational potential for non-invasive assessment of mitochondrial function in living brains across the lifespan.

bioengineering↗

bioRxiv2024

Modeling Normal Mouse Uterine Contraction and Placental Perfusion with Non- invasive Longitudinal Dynamic Contrast Enhancement MRI

The placenta is a transient organ critical for fetal development. Disruptions of normal placental functions can impact health throughout an individuals entire life. Although being recognized by the NIH Human Placenta Project as an important organ, the placenta remains understudied, partly because of a lack of non-invasive tools for longitudinally evaluation for key aspects of placental functionalities. Non-invasive imaging that can longitudinally probe murine placental health in vivo are critical to understanding placental development throughout pregnancy. We developed advanced imaging processing schemes to establish functional biomarkers for non-invasive longitudinal evaluation of placental development. We developed a dynamic contrast enhancement magnetic resonance imaging (DCE-MRI) pipeline combined with advanced image process methods to model uterine contraction and placental perfusion dynamics. Our novel imaging pipeline uses subcutaneous administration of gadolinium for steepest-slope based perfusion evaluation. This enables non-invasive longitudinal monitoring. Additionally, we advance the placental perfusion chamber paradigm with a novel physiologically-based threshold model for chamber localization and demonstrate spatially varying placental chambers using multiple functional metrics that assess mouse placental development and continuing remodeling throughout gestation. Lastly, using optic flow to quantify placental motions arisen from uterine contractions in conjunction with time-frequency analysis, we demonstrated that the placenta exhibited asymmetric contractile motion.

systems biology↗

bioRxiv2021

Seascape genomics reveals metapopulation connectivity network of Paramuricea biscaya in the northern Gulf of Mexico

The degree of connectivity among populations influences their ability to respond to natural and anthropogenic stressors. In marine systems, determining the scale, rate, and directionality of larval dispersal is therefore central to understanding how coral metapopulations are interconnected and the degree of resiliency in the event of a localized disturbance. Understanding these source-sink dynamics is essential to guide restoration efforts and for the study of ecology and evolution in the ocean. The patterns and mechanisms of connectivity in the deep-sea (> 200 meters deep) are largely understudied. In this study, we investigated the spatial diversity patterns and metapopulation connectivity of the octocoral Paramuricea biscaya throughout the northern Gulf of Mexico (GoM). Paramuricea biscaya is one of the most abundant corals on the lower continental slope (between 1200 and 2500 m) in the GoM. The 2010 Deepwater Horizon oil spill (DWH) directly impacted populations of this species and thus are considered primary targets for restoration. We used a combination of seascape genomic analyses, high-resolution ocean circulation modeling, and larval dispersal simulations to quantify the degree of population structuring and connectivity among P. biscaya populations. Evidence supports the hypotheses that the genetic diversity of P. biscaya is predominantly structured by depth, and that larval dispersal among connected populations is asymmetric due to dominant ocean circulation patterns. Our results suggest that there are intermediate unsampled populations in the central GoM that serve as stepping stones for dispersal. The data suggest that the DeSoto Canyon area, and possibly the West Florida Escarpment, critically act as sources of larvae for areas impacted by the DWH oil spill in the Mississippi Canyon. This work illustrates that the management of deep-sea marine protected areas should incorporate knowledge of connectivity networks and depth-dependent processes throughout the water column.

ecology↗

bioRxiv2021

Integrative Clinical and Molecular Characterization of Translocation Renal Cell Carcinoma

ABSTRACTTranslocation renal cell carcinoma (tRCC) is an aggressive and poorly-characterized subtype of kidney cancer driven by MiT/TFE gene fusions. Here, we define the landmarks of tRCC through an integrative analysis of 152 tRCC patients identified across multiple genomic, clinical trial, and retrospective cohorts. Most tRCCs harbor few somatic alterations apart from MiT/TFE fusions and homozygous deletions at chromosome 9p21.3 (19.2% of cases). Transcriptionally, tRCCs display a heightened NRF2-driven antioxidant response that is associated with resistance to many targeted therapies. Consistently, we find that outcomes for tRCC patients treated with vascular endothelial growth factor receptor inhibitors (VEGFR-TKI) are worse than those treated with immune checkpoint inhibition (ICI). Multiparametric immunofluorescence confirmed the presence of CD8 + tumor-infiltrating T cells compatible with a clinical benefit from ICI and revealed an exhaustion immunophenotype distinct from clear cell RCC. Our findings comprehensively define the clinical and molecular features of tRCC and may inspire new therapeutic hypotheses.

cancer biology↗