Biology subjects

Brown, R. J.

Publications and source records attributed to Brown, R. J..

4 recordsLinked to original sources

bioRxiv2024

antiCD49d Ab treatment ameliorates age-associated inflammatory response and mitigates CD8 T cell cytotoxicity after traumatic brain injury

Patients aged 65 years and older account for an increasing proportion of patients with traumatic brain injury (TBI). Older TBI patients experience increased morbidity and mortality compared to their younger counterparts. Our prior data demonstrated that by blocking 4 integrin, anti-CD49d antibody (aCD49d Ab) abrogates CD8+ T-cell infiltration into the injured brain, improves survival, and attenuates neurocognitive deficits. Here, we aimed to uncover how aCD49d Ab treatment alters local cellular responses in the aged mouse brain. Consequently, mice incur age-associated toxic cytokine and chemokine responses long-term post-TBI. aCD49d Ab attenuates this response along with a T helper (Th)1/Th17 immunological shift and remediation of overall CD8+ T cell cytotoxicity. Furthermore, aCD49d Ab reduces CD8+ T cells exhibiting higher effector status, leading to reduced clonal expansion in aged, but not young, mouse brains with chronic TBI. Together, aCD49d Ab is a promising therapeutic strategy for treating TBI in the older people. Graphic abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=88 SRC="FIGDIR/small/596673v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@97311aorg.highwire.dtl.DTLVardef@18a86borg.highwire.dtl.DTLVardef@d9162forg.highwire.dtl.DTLVardef@3f8d06_HPS_FORMAT_FIGEXP M_FIG C_FIG Aged brains after TBI comprise two pools of CD8+ T cells. The aged brain has long been resided by a population of CD8+ T cells thats exhaustive and dysfunctional. Post TBI, due to BBB impairment, functional CD8+ T cells primarily migrate into the brain parenchyma. Aged, injury-associated microglia with upregulated MHC class I molecules can present neoantigens such as neuronal and/or myelin debris in the injured brains to functional CD8+ T, resulting in downstream CD8+ T cell cytotoxicity. aCD49d Ab treatment exerts its function by blocking the migration of functional effector CD8+ T cell population, leading to less cytotoxicity and resulting in improved TBI outcomes in aged mice.

immunology↗

bioRxiv2021

Strontium isotopes reveal diverse life history variations, migration patterns, and habitat use for Broad Whitefish (Coregonus nasus) in Arctic, Alaska

Conservation of Arctic fish species is challenging partly due to our limited ability to track fish through time and space, which constrains our understanding of life history diversity and lifelong habitat use. Broad Whitefish (Coregonus nasus) is an important subsistence species for Alaskas Arctic Indigenous communities, yet little is known about life history diversity, migration patterns, and freshwater habitat use. Using laser ablation Sr isotope otolith microchemistry, we analyzed Colville River Broad Whitefish 87Sr/86Sr chronologies (n = 61) to reconstruct movements and habitat use across the lives of individual fish. We found evidence of at least six life history types, including three anadromous types, one semi-anadromous type, and two nonanadromous types. Anadromous life history types comprised a large proportion of individuals sampled (collectively, 59%) and most of these (59%) migrated to sea between ages 0-2 and spent varying durations at sea. The semi-anadromous life history type comprised 28% of samples and entered marine habitat as larvae. Nonanadromous life history types comprised the remainder (collectively, 13%). Otolith 87Sr/86Sr data from juvenile and adult freshwater stages suggest that habitat use changed in association with age, seasons, and life history strategies. This information on Broad Whitefish life histories and habitat use across time and space will help managers and conservation planners better understand the risks of anthropogenic impacts and help conserve this vital subsistence resource.

ecology↗

bioRxiv2018

Total lung capacity without plethysmography

BackgroundAmong the most basic measures of respiratory function is the total lung capacity (TLC). TLC is the pulmonary gas volume at maximal lung inflation, which is the sum of the volume of gas that can be exhaled -the vital capacity (VC)- and the volume of gas that cannot -the residual volume (RV). Determination of VC requires only spirometry whereas determination of RV or TLC requires body plethysmography, gas dilution or washout, or thoracic imaging, each of which is more complex than spirometry, and none of which is suited to routine office practice, population screening, or community medicine. To fill this gap, we describe here a new approach to determine TLC without plethysmography.\n\nMethodsIn a heterogeneous population of 434 volunteers (265 male, 169 female; 201 healthy, 170 with airflow obstruction, and 63 with ventilatory restriction), we determined TLC in the standard fashion using conventional body plethysmography (TLCpleth). In the same individuals, we also determined TLC in a novel fashion using the MiniBox (TLCMB). To obtain TLCMB, population-based data from traditional spirometry together with flow-interruption transients were subjected to data mining and machine-learning to create for each individual subject an unbiased statistical determination of TLC.\n\nResultsFor the combined heterogeneous population, we found TLCpleth = 1.02TLCMB -0.091 L, adjusted r2=0.824. For the heterogeneous population as a whole, and for each subpopulation, TLCMB closely tracked TLCpleth. For 26 healthy subjects measured on different days, the coefficient of variation for repeated measurements in was 3.3% for TLCpleth versus 1.6% for TLCMB.\n\nConclusionsThese results establish the validity and potential utility of a new method for rapid, accurate, and repeatable determination of TLC in a heterogeneous patient population, but without the need of a plethysmograph.

bioengineering↗

bioRxiv2018

Neural representations of aversive value encoding in pain catastrophizers

Chronic pain is exacerbated by maladaptive cognition such as pain catastrophizing (PC). Biomarkers of PC mechanisms may aid precision medicine for chronic pain. Here, we investigate EEG biomarkers using mass univariate and multivariate (machine learning) approaches. We test theoretical notions that PC results from a combination of augmented aversive-value encoding (\"magnification\") and persistent expectations of pain (\"rumination\"). Healthy individuals with high or low levels of PC underwent an experimental pain model involving nociceptive laser stimuli preceded by cues predicting forthcoming pain intensity. Analysis of EEG acquired during the cue and laser stimulation provided event-related potentials (ERPs) identifying spatially and temporally-extended neural representations associated with pain catastrophizing. Specifically, differential neural responses to cues predicting high vs. low intensity pain (i.e. aversive value encoding) were larger in the high PC group, largely originating from mid-cingulate and superior parietal cortex. Multivariate spatiotemporal EEG patterns evoked from cues with high aversive value selectively and significantly differentiated the high PC from low PC group (64.6% classification accuracy). Regression analyses revealed that neural patterns classifying groups could be partially predicted (R2 = 28%) from those neural patterns classifying the aversive value of cues. In contrast, behavioural and EEG analyses did not provide evidence that PC modifies more persistent effects of prior expectation on pain perception and nociceptive responses. These findings support the hypothesis of magnification of aversive value encoding but not persistent expression of expectation in pain catastrophizers. Multivariate patterns of aversive value encoding provide promising biomarkers of maladaptive cognitive responses to chronic pain that have future potential for psychological treatment development and clinical stratification.

neuroscience↗