Biology subjects

Drummond, G.

Publications and source records attributed to Drummond, G..

4 recordsLinked to original sources

bioRxiv2024

Diversity of ancestral brainstem noradrenergic neurons across species and multiple biological factors

The brainstem cell group, locus coeruleus (LC), is present across vertebrates and influences cardiorespiratory, metabolic, immune, and cognitive functions by activating in two putatively distinct firing patterns. Yet, the degree to which the LC firing rates and patterns are homogenous across species has never been assessed due to inherently limited sample sizes. To remedy this, we pooled cross-species data from 20 laboratories to show that firing rates differ across species and are modulated by sex, age, and type of in vitro or in vivo preparation. Contrary to the prevailing dual-mode firing pattern schema, we observed patterns spread across a low-dimensional manifold, with subregions enriched for specific biological factors and neurodegenerative disease models. Our findings show considerable diversity in an ancestral vertebrate neuromodulatory system.

neuroscience↗

bioRxiv2019

Ultrafast immunostaining of organ-scale tissues for scalable proteomic phenotyping

Studying the function and dysfunction of complex biological systems necessitates comprehensive understanding of individual cells. Advancements in three-dimensional (3D) tissue processing and imaging modalities have enabled rapid visualization and phenotyping of cells in their spatial context. However, system-wide interrogation of individual cells within large intact tissue remains challenging, low throughput, and error-prone owing to the lack of robust labeling technologies. Here we introduce a rapid, versatile, and scalable method, eFLASH, that enables complete and uniform labeling of organ-scale tissue within one day. eFLASH dynamically modulates chemical transport and reaction kinetics to establish system-wide uniform labeling conditions throughout the day-long labeling period. This unique approach enables the same protocol to be compatible with a wide range of tissue types and probes, enabling combinatorial molecular phenotyping across different organs and species. We applied eFLASH to generate quantitative maps of various cell types in mouse brains. We also demonstrated multidimensional cell profiling in a marmoset brain block. We envision that eFLASH will spur holistic phenotyping of emerging animal models and disease models to help assess their functions and dysfunctions.

bioengineering↗

bioRxiv2019

Scalable image processing techniques for quantitative analysis of volumetric biological images from light-sheet microscopy

Here we describe an image processing pipeline for quantitative analysis of terabyte-scale volumetric images of SHIELD-processed mouse brains imaged with light-sheet microscopy. The pipeline utilizes open-source packages for destriping, stitching, and atlas alignment that are optimized for parallel processing. The destriping step removes stripe artifacts, corrects uneven illumination, and offers over 100x speed improvements compared to previously reported algorithms. The stitching module builds upon Terastitcher to create a single volumetric image quickly from individual image stacks with parallel processing enabled by default. The atlas alignment module provides an interactive web-based interface that automatically calculates an initial alignment to a reference image which can be manually refined. The atlas alignment module also provides summary statistics of fluorescence for each brain region as well as region segmentations for visualization. The expected runtime of our pipeline on a whole mouse brain hemisphere is 1-2 d depending on the available computational resources and the dataset size.

bioengineering↗

bioRxiv2018

Predictive validity of effective shunt fraction in critically ill patients

Accurate measurement of pulmonary oxygenation is important for classification of disease severity and quantification of outcomes in clinical studies. We compared predictive validity of established tension-based methods with two new measures of shunt fraction: (1) a non-invasive effective shunt (ES); and (2) inferred values from an integrated mathematical model of gas exchange (DB). Median absolute error (MAE) values for the four measures considered were: alveolar-arterial difference, 7.30kPa; PaO2/FIO2 ratio, 2.41kPa; DB, 2.13kPa; ES: 1.88kPa. ES performed significantly better than other measures (p<10-10 in all comparisons). While the simplicity of P/F is suitable for routine use, the superior predictive validity of ES should make this measure the preferred choice where physiological accuracy is important, such as for use as surrogate outcome in clinical research.

physiology↗