Biology subjects

Hartman, R.

Publications and source records attributed to Hartman, R..

6 recordsLinked to original sources

bioRxiv2025

Longitudinal Metabolomic Profiling of Biogenic Amines in Plasma and CSF, and Their Correlation, Reveals Sex-Specific and Age Changes in TgF344 Alzheimer's Disease Transgenic and Wildtype Rats

BackgroundAlterations in amine metabolism have been implicated Alzheimers disease (AD). Cerebrospinal fluid (CSF) and plasma are key biofluids in AD research. CSF is considered to better reflect brain metabolic alterations than plasma, while plasma can be obtained more easily. However, plasma-CSF relationships are unclear. AimTo investigate longitudinal changes of amines in plasma and CSF, and their correlation across the two, in male and female TgF344 AD transgenic versus wildtype (WT) rats. MethodLC-MS-based targeted metabolomics was used to analyze 60 and 55 amines in plasma and CSF, respectively, of male and female TgF344-AD and WT rats, at 12, 25, 50 and 85 weeks. Statistical analysis was performed using generalized logistic regressions, Pearson correlations, and differential correlations between groups and matrixes. ResultsCompared to WT controls, at 12 weeks, TgF344-AD rats showed an increase of 3-methylhistidine, anserine, cysteine, s-methylcysteine, while at 25 weeks, male TgF344-AD rats showed pronounced increases in CSF levels of alpha-aminobutyric acid, asparagine, glycylglycine, glycylproline, histidine, isoleucine, kynurenine, leucine, methionine, methionine sulfone, norepinephrine, phenylalanine, proline, tyrosine, and valine. At 50 weeks, female TgF344-AD rats exhibited reductions in CSF for DL-3-aminoisobutyric acid, gamma-aminobutyric acid, ornithine, and putrescine. Distinct plasma-CSF correlations were found for 1-methylhistidine, 2-aminoadipic acid, putrescine, kynurenine, N6,N6,N6-trimethyl-lysine, DL-3-aminoisobutyric acid, and taurine, particularly in TgF344-AD rats. ConclusionsBody fluid, age- and sex-dependent amine alterations in CSF and plasma of TgF344-AD rats compared to WT controls provide important insights into AD disease processes and may aid early diagnosis and therapeutic targeting.

systems biology↗

bioRxiv2025

Lipidomic Fingerprints Reveal Sex-, Age-, and Disease-Dependent Differences in the TgF344-AD Transgenic Rats

BackgroundGathering information on Alzheimers disease (AD) progression in human poses significant challenges due to the lengthy timelines and ethical considerations involved. Animal AD models provide a valuable alternative for conducting mechanistic studies and testing potential therapeutic strategies. Disturbed lipid homeostasis is among the earliest neuropathological features of AD. AimTo identify longitudinal plasma lipidomic changes associated with age, sex, and AD in male and female TgF344-AD and wild-type rats. MethodsA total of 751 lipids in 141 rats (n=73 TgF344-AD; n= 68 WT) were quantified at 12, 25, 50, and 85 weeks). Differential abundances of lipids were assessed using generalized logical regression models, correcting for i) age and sex, for ii) individual age groups, and iii) sex-specific differences. Predictive lipid signature models for AD were developed using stepwise feature selection for the full age range, as well as for midlife. ResultsSex differences were identified among all ages in sphingomyelin (SM), phosphatidylcholine (PC), and phosphatidylethanolamine (PE) lipid classes. AD and age-related differences were found in the SM class in mid-life (25-50 weeks). Other AD and age-related differences were found in the ratios of linoleic acid and 5 of its products. Moreover, similarities in lipidomic profile changes were observed for humans and rats. The full age range and mid-life predictive lipid signatures for AD resulted in an AUC of 0.75 and 0.68, respectively. ConclusionsOur findings highlight the value of lipidomic in identifying early AD-related lipid alterations, offering a promising avenue for understanding disease mechanisms and advancing biomarker discovery.

systems biology↗

bioRxiv2024

Intraguild predation among snails drives human schistosome amplification despite susceptible host regulation

Competitors and predators of hosts have the potential to alter transmission dynamics within host- parasite systems. Biocontrol aims to harness these effects to mitigate diseases of human or agricultural importance, but without a detailed understanding of the mechanisms of how hosts and non-hosts interact over time these attempts may backfire. We investigated the role that two resource competitors that have been employed in biocontrol, Melanoides tuberculata and Physa acuta, play in the Biomphalaria glabrata-Schistosoma mansoni system. We created experimental communities with differing compositions in mesocosms and tracked resource availability, host snail abundance, size, reproduction, and parasite production over 16 weeks. We found that Melanoides acted as a typical, albeit weak, resource competitor of Biomphalaria, reducing host body size and per capita cercarial production but with no appreciable influence on host abundance. Physa, however, reduced host abundance but increased resource availability and cercarial production, which represents biocontrol failure and is inconsistent with solely acting as a resource competitor. In follow-up experiments, we determined that Physa is a voracious consumer of host eggs. We then built a model representing this intraguild predation effect, which was able to explain these initially counterintuitive results. These divergent results from two putative resource competitors of host snails underscore the importance of establishing the mechanisms through which hosts, non-hosts, and parasites interact, especially for anticipating the potential outcomes of biocontrol interventions.

ecology↗

bioRxiv2021

Long noncoding RNA VENTHEART is required for cardiomyocyte specification and function

RationaleLong noncoding RNAs (lncRNAs) control cardiac gene expression during heart development and disease. It is accordingly plausible for the same lncRNA to regulate both cardiac development, as well as play a role in adult heart disease progression. lncRNA regulators of early cardiomyocyte (CM) lineage commitment have been identified and characterised, however those controlling later CM specification remain unknown. ObjectivesIn this study we identified a novel lncRNA required for CM specification, maturation and function, and also discovered its suggested relevance to heart disease. Methods and ResultsWe performed single cell RNA-seq on human embryonic stem cell derived cardiomyocytes at 2, 6 and 12 weeks of differentiation. Weighted correlation network analysis (WGCNA) identified core gene modules, including lncRNAs highly abundant and uniquely expressed in the human heart. A lncRNA (we call VENTHEART, VHRT) co-expressed with cardiac maturation and ventricular-specific genes MYL2 and MYH7, as well as in adult human ventricular tissue. CRISPR-mediated excision of VHRT led to impaired CM sarcomere formation, and loss of the CM specification gene program. VHRT knockdown (KD) in hESC-CMs confirmed its regulatory role for key cardiac contraction, calcium hemostasis and heart development genes, including MYH6 and RYR2. Functional evaluation after VHRT KD using impedance-based technology and action potential recordings, proved reduced contraction amplitude and loss of the ventricular-like action potential in CM, respectively. Through an integrative analysis of genome-wide association studies (GWAS), expression quantitative trait locus (eQTL) and gene co-expression network, we found VHRT to be co-regulated with core cardiac contractile genes, and the likely source of a heart failure genetic association signal overlapping the VHRT gene locus. Finally, VHRT KD and human failing heart transcriptome comparison validates the consistent downregulation again of cardiac contractile and calcium regulatory genes (P<0.05). ConclusionWe conclude that VHRT lncRNA is required for proper CM specification and function. Furthermore, reduced VHRT may contribute to the development or progression of human heart disease.

cell biology↗

bioRxiv2020

Evaluation of a large-scale flow manipulation to the upper San Francisco Estuary: Response of habitat conditions for an endangered native fish

While flow is known to be a major driver of estuarine ecosystems, targeted flow manipulations are rare because tidal systems are extremely variable in space and time, and because the necessary infrastructure is rarely available. In summer 2018 we used a unique water control structure in the San Francisco Estuary (SFE) to direct a managed flow pulse into Suisun Marsh, one of the largest contiguous tidal marshes on the west coast of the United States. The action was designed to increase habitat suitability for the endangered Delta Smelt Hypomesus transpacificus, a small osmerid fish endemic to the upper SFE. The approach was to operate the Suisun Marsh Salinity Control Gates (SMSCG) in conjunction with increased Sacramento River tributary inflow to direct an estimated 160 x 106 m3 pulse of low salinity water into Suisun Marsh during August, a critical time period for juvenile Delta Smelt rearing. Three-dimensional modeling showed that directing additional low salinity water into Suisun Marsh ("Flow Action") substantially increased the area of low salinity habitat for Delta Smelt that persisted beyond the period of SMSCG operations. Field monitoring showed that turbidity and chlorophyll were at higher levels in Suisun Marsh, representing better habitat conditions, than the upstream Sacramento River region throughout the study period. The Flow Action had no substantial effects on zooplankton abundance, nor did Suisun Marsh show enhanced levels of these prey species in comparison to the Sacramento River. Fish monitoring data suggested that small numbers of Delta Smelt colonized Suisun Marsh from the Sacramento River during the Flow Action, further supporting our hypothesis that the Flow Action would benefit this rare species. Our study provides insight into both the potential use of targeted flow manipulations to support endangered fishes such as Delta Smelt, and into the general response of estuarine habitat to flow management.

ecology↗

bioRxiv2019

Characterizing macroinvertebrate community composition and abundance in freshwater tidal wetlands of the Sacramento-San Joaquin Delta

Restored tidal wetlands may provide important food web support for at-risk fish species in the Sacramento-San Joaquin Delta (Delta) of California, including Delta Smelt (Hypomesus transpacificus) and Chinook Salmon (Oncorhynchus tshawytscha). Since many tidal wetland restoration projects are planned or have recently been constructed in the Delta, understanding the diversity and variability of wetland invertebrates that are fish prey items is of increasing importance. During this study, two different invertebrate sampling techniques were tested (leaf packs and sweep nets) in four habitat types within three different wetland sites to evaluate which sampling technique provided the most reliable metric of invertebrate abundance and community composition. Sweep nets provided a better measure of fish food availability than leaf packs and were better able to differentiate between habitat types. Generalized linear models showed submerged and floating vegetation had higher abundance and species richness than channel habitats or emergent vegetation. Permutational multivariate analysis of variance showed significantly different communities of invertebrates in different habitat types and in different wetlands, and point-biserial correlation coefficients found a greater number of mobile taxa associated with sweep nets. There were more taxa associated with vegetated habitats than channel habitats, and one region had more taxa associated with it than the other two regions. These results suggest that restoration sites that contain multiple habitat types may enhance fish invertebrate prey diversity and resilience. However, the effect of habitat diversity must be monitored as restoration sites develop to assess actual benefits to at-risk fish species.

ecology↗