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Toussaint, A.

Publications and source records attributed to Toussaint, A..

7 recordsLinked to original sources

Remote automated delivery of mechanical stimuli coupled to brain recordings in behaving mice

The canonical framework for testing pain and mechanical sensitivity in rodents is manual delivery of stimuli to the paw. However, this approach is time consuming, produces variability in results, requires significant training, and is ergonomically unfavorable to the experimenter. To circumvent limitations in manual delivery of stimuli, we have created a device called the ARM (Automated Reproducible Mechano-stimulator). Built using a series of linear stages, cameras, and stimulus holders, the ARM is more accurate at hitting the desired target, delivers stimuli faster, and decreases variability in delivery of von Frey hair filaments. We demonstrate that the ARM can be combined with traditional measurements of pain behavior and automated machine-learning based pipelines. Importantly, the ARM enables remote testing of mice with experimenters outside the testing room. Using remote testing, we found that mice habituated more quickly when an experimenter was not present and experimenter presence leads to significant sex-dependent differences in paw withdrawal and pain associated behaviors. Lastly, to demonstrate the utility of the ARM for neural circuit dissection of pain mechanisms, we combined the ARM with cellular-resolved microendoscopy in the amygdala, linking stimulus, behavior, and brain activity of amygdala neurons that encode negative pain states. Taken together, the ARM improves speed, accuracy, and robustness of mechanical pain assays and can be combined with automated pain detection systems and brain recordings to map central control of pain.

neuroscience↗

Behavioral fingerprinting of the naked mole-rat uncovers signatures of eusociality and social touch

The East African naked mole-rat (Heterocephalus glaber) lives in cooperative subterranean colonies and displays a capacity to recognize social novelty, rank, and identity. The sensory cues used for social recognition remain poorly understood, especially because many of their senses are either lost or greatly reduced in comparison to other mammals. Here, we found that naked mole-rats actively touch faces 100% of the time they encounter one another in a tunnel test, followed by milliseconds speed determination of the rank of the other animal. Even in an open arena, naked mole-rats engage in face-to-face touch hundreds of times in a 10-minute social pairing and colonies do so tens of thousands of times over a 24-hour period in their home environment. To demonstrate the prominence of face touch at a molecular level, we show that social housing conditions lead to widespread activation of mechanosensory ion channels, including Piezo2, in neurons that innervate the face, but not the body. Lastly, to determine the ethological relevance of face touch, we reduced its capacity with facial whisker trimming and revealed an apparent inability for animals to recognize colony members. Together, these findings uncover face touch as a prominent social behavior in naked mole-rats that is intimately linked to social recognition.

neuroscience↗

Injury Severity is a Key Contributor to Coagulation Dysregulation and Fibrinogen Consumption

BackgroundTraumatic injury is a leading cause of death for those under the age of 45, with 40% occurring due to hemorrhage. Severe tissue injury and hypoperfusion lead to marked changes in coagulation, thereby preventing formation of a stable blood clot and increasing hemorrhage associated mortality. ObjectivesWe aimed to quantify changes in clot formation and mechanics occurring after traumatic injury and the relationship to coagulation kinetics, and fibrinolysis. MethodsPlasma was isolated from injured patients upon arrival to the emergency department. Coagulation kinetics and mechanics of healthy donors and patient plasma were compared with rheological, turbidimetric and thrombin generation assays. ELISAs were performed to determine tissue plasminogen activator (tPA) and D-dimer concentration, as fibrinolytic markers. ResultsSixty-three patients were included in the study. The median injury severity score (ISS) was 17, median age was 37.5 years old, and mortality rate was 30%. Rheological, turbidimetric and thrombin generation assays indicated that trauma patients on average, and especially deceased patients, exhibited reduced clot stiffness, increased fibrinolysis and reduced thrombin generation compared to healthy donors. Fibrinogen concentration, clot stiffness, D-dimer and tPA all demonstrated significant direct correlation to increasing ISS. Machine learning algorithms identified and highlighted the importance of clinical factors on determining patient outcomes. ConclusionsViscoelastic and biochemical assays indicate significant contributors and predictors of mortality for improved patient treatment and therapeutic target detection. ESSENTIALSO_LITraumatic injury may lead to alterations in a patients ability to form stable blood clots C_LIO_LIA study was performed to assess how trauma severity affects coagulation kinetics C_LIO_LIKey alterations were observed in trauma patients, who exhibit weaker and slower forming clots C_LIO_LIPaired with machine learning methods, the results indicate key aspects contributing to mortality C_LI

bioengineering↗

Combining taxonomic, phylogenetic and functional diversity reveals new global priority areas for tetrapod conservation

Human activities have eroded biodiversity, yet the varying influence of past versus recent impacts across the distinct facets of biodiversity is still poorly understood. Weighting taxonomic information by phylogenetic and functional diversity in a novel multifaceted index (-Diversity) across more than 17,000 tetrapod species, we show the geography of multifaceted tetrapod diversity, and the role of climate stability and water-energy dynamics coupled with the timing of inception of agriculture in explaining broad-scale patterns of tetrapod diversity. In particular, the varying geography of the timing of agriculture expansion since the Neolithic affected -Diversity at least as much as recent human impacts, especially in birds, mammals, and reptiles, suggesting that human imprints may have shaped tetrapod diversity for millennia through legacy effects of past land use modifications. The long-lasting effect of humans will only accelerate, as the most diverse areas for -Diversity (tropical Africa, South East Asia and Central and South America) are disproportionally exposed to both future climate and land-use change.

ecology↗

Elevated CO2 reduces a common soybean leaf endophyte

Free-air CO2 enrichment (FACE) experiments have elucidated how climate change affects plant physiology and production. However, we lack a predictive understanding of how climate change alters interactions between plants and endophytes, critical microbial mediators of plant physiology and ecology. We leveraged the SoyFACE facility to examine how elevated [CO2] affected soybean (Glycine max) leaf endophyte communities in the field. Endophyte community composition changed under elevated [CO2], including a decrease in the abundance of a common endophyte, Methylobacterium sp. Moreover, Methylobacterium abundance was negatively correlated with co-occurring fungal endophytes. We then assessed how Methylobacterium affected the growth of co-occurring endophytic fungi in vitro. Methylobacterium antagonized most co-occurring fungal endophytes in vitro, particularly when it was more established in culture before fungal introduction. Variation in fungal response to Methylobacterium within a single fungal operational taxonomic unit (OTU) was comparable to inter-OTU variation. Finally, fungi isolated from elevated vs. ambient [CO2] plots differed in colony growth and response to Methylobacterium, suggesting that increasing [CO2] may affect fungal traits and interactions within the microbiome. By combining in situ and in vitro studies, we show that elevated [CO2] decreases the abundance of a common bacterial endophyte that interacts strongly with co-occurring fungal endophytes. We suggest that endophyte responses to global climate change will have important but largely unexplored implications for both agricultural and natural systems.

ecology↗

Mapping extinction risk in the global functional spectra across the tree of life

Although one quarter of the species of plants and vertebrates are threatened with extinction, little is known about how the potential effect of extinctions on the global diversity of ecological strategies. Using trait and phylogenetic information for more than 75,000 species of plants, mammals, birds, reptiles, amphibians and freshwater fishes, we characterized the global functional spectra of each of these groups. Mapping of extinction risk within these spectra revealed that larger species with slower pace of life are universally threatened. Simulated potential extinctions revealed extensive internal reorganizations in the global functional spectra, which are particularly severe for mammals and amphibians. Considering the disproportionate importance of the largest species for ecological processes, our results emphasize the importance of actions to prevent the extinction of the megabiota.Competing Interest StatementThe authors have declared no competing interest.View Full Text

ecology↗

Differential physiological role of BIN1 isoforms in skeletal muscle development, function and regeneration

Skeletal muscle development and regeneration are tightly regulated processes. How the intracellular organization of muscle fibers is achieved during these steps is unclear. Here we focus on the cellular and physiological roles of amphiphysin 2 (BIN1), a membrane remodeling protein mutated in both congenital and adult centronuclear myopathies, that is ubiquitously expressed and has skeletal muscle-specific isoforms. We created and characterized constitutive, muscle-specific and inducible Bin1 homozygous and heterozygous knockout mice targeting either ubiquitous or muscle-specific isoforms. Constitutive Bin1-deficient mice died at birth from lack of feeding due to a skeletal muscle defect. T-tubules and other organelles were misplaced and altered, supporting a general early role of BIN1 on intracellular organization in addition to membrane remodeling. Whereas restricted deletion of Bin1 in unchallenged adult muscles had no impact, the forced switch from the muscle-specific isoforms to the ubiquitous isoforms through deletion of the in-frame muscle-specific exon delayed muscle regeneration. Thus, BIN1 ubiquitous function is necessary for muscle development and function while its muscle-specific isoforms fine-tune muscle regeneration in adulthood, supporting that BIN1 centronuclear myopathy with congenital onset are due to developmental defects while later onset may be due to regeneration defects.

pathology↗