Biology subjects

Savage, C. R.

Publications and source records attributed to Savage, C. R..

6 recordsLinked to original sources

bioRxiv2026

Concussion decreases brain signal variability

Sports-related concussion represents a major public health concern, with millions of cases diagnosed annually. Despite significant methodological advances in functional brain imaging, a clinically meaningful neuroimaging biomarker of concussion has yet to be established. This may be due in part to a reliance on traditional measures. For example, approaches examining mean activation across trials reduce responses to a single measure of central tendency and therefore fail to capture important individual differences. In contrast, blood oxygenation level dependent (BOLD) variability offers a promising new approach to measuring brain function, Specifically, it captures individual differences in the temporal variability in the BOLD signal over time. Further, it is sensitive to neural, vascular, and neurovascular coupling changes that accompany concussion. We collected baseline (prior to injury) and post-concussion (within 48 hours of injury) neuroimaging data in 56 collegiate athletes. Within this longitudinal dataset, we investigated changes in BOLD variability across multiple spatial scales. In addition, we examined their relationships with self-reported symptoms and cognitive performance. As expected, symptoms increased following concussion while computerized cognitive performance declined. BOLD variability decreased from baseline to post-concussion, particularly in the somatomotor and language networks. Moreover, changes in BOLD variability were related to changes in symptom reporting and cognitive performance. Together, these findings advance our understanding of how concussion affects brain function and highlight BOLD signal variability as a promising biomarker to aid ongoing efforts to improve the diagnosis and treatment of sports-related concussion.

neuroscience↗

bioRxiv2026

16S ribosomal RNA modification drives transcript-specific translation efficiency

Bacterial ribosomal RNAs (rRNAs) are decorated with conserved nucleotide modifications, but the functionality of these modifications is often underexplored. MraW (RsmH) is a 16S rRNA methyltransferase that fine-tunes ribosomal function. We identified a loss-of-function allele in mraW that corrected a late-stage sporulation defect in Bacillus subtilis by bypassing a key sporulation checkpoint via altered translational regulation. Purified ribosomes isolated from {Delta}mraW cells displayed a [~]2-fold decrease in translation efficiency; in vivo, {Delta}mraW cells produced decreased levels of the sporulation checkpoint protein CmpA. This regulation was mediated by sequences from the 5 untranslated region and the coding sequence of cmpA, which form a step-loop structure that occlude early codons of the mRNA. Proteomic analysis revealed that MraW directly or indirectly regulates the production of multiple proteins, some of which form similar structural elements as the cmpA transcript. We propose that MraW modification of 16S rRNA enhances translation efficiency in general, and that specific transcripts, whose gene products are likely required in limiting quantities, have evolved structural features that act as a regulatory mechanism to govern protein levels. This type of regulation may be most apparent in bacteria which exhibit uncoupled transcription and translation. HIGHLIGHTSO_LIA conserved 16S rRNA modification enhances translation of structured mRNAs C_LIO_LIEarly mRNA stem-loops impose translational control dependent on ribosome modification C_LIO_LImRNA structure and rRNA modifications likely co-evolved to fine-tune protein dosage C_LI

microbiology↗

bioRxiv2026

Cognitive reappraisal of food and emotion cues involves common and unique neural contributions

Obesity is a growing public health concern with more than 40% of adults meeting criteria for obesity in the United States. Although many treatments seek to lower individuals weight, few treatments have focused on cognitive strategies to change the way individuals think about food, therefore, decreasing consumption of non-nutrient-dense foods. Cognitive reappraisal is one strategy that involves changing the way one thinks about a situation and can be used to downregulate responses to those stimuli. Leveraging this intuitive, cost-effective strategy to decrease ones desire to eat unhealthy food and therefore, decrease overeating, could improve physical and mental health. The present study identified brain regions that are differentially activated when using cognitive reappraisal to downregulate responses to food (FR) versus when using the same strategy to downregulate negative emotions (ER). We collected functional magnetic resonance imaging (fMRI) data in 63 undergraduate students while participants completed both tasks. There was increased reappraisal-related activation in widespread regions across both tasks, including in expected subcortical (i.e., striatum) and cortical areas (i.e., visual, frontoparietal). We also found domain-specific activity, with greater insula activation in the FR than the ER task and greater hippocampal activation in the ER than the FR task. These results reveal domain-general and domain-specific effects of cognitive reappraisal in FR and ER tasks that inform future work examining eating behavior. Taken together, a better explication of the overlapping and discrete processes of food regulation, as it compares to other applications of this regulatory strategy can inform new intervention targets.

neuroscience↗

bioRxiv2024

Second language learning in older adults modulates Stroop task performance and brain activation

Numerous studies have highlighted cognitive benefits in lifelong bilinguals during aging, manifesting as superior performance on cognitive tasks compared to monolingual counterparts. Yet, the cognitive impacts of acquiring a new language in older adulthood remain unexplored. In this study, we assessed both behavioral and fMRI responses during a Stroop task in older adults, pre- and post language-learning intervention. A group of 41 participants (age:60-80) from a predominantly monolingual environment underwent a four-month online language course, selecting a new language of their preference. This intervention mandated engagement for 90 minutes a day, five days a week. Daily tracking was employed to monitor progress and retention. All participants completed a color-word Stroop task inside the scanner before and after the language instruction period. We found that performance on the Stroop task, as evidenced by accuracy and reaction time, improved following the language learning intervention. With the neuroimaging data, we observed significant differences in activity between congruent and incongruent trials in key regions in the prefrontal and parietal cortex. These results are consistent with previous reports using the Stroop paradigm. We also found that the amount of time participants spent with the language learning program was related to differential activity in these brain areas. Specifically, we found that people who spent more time with the language learning program showed a greater increase in differential activity between congruent and incongruent trials after the intervention relative to before. Future research is needed to determine the optimal parameters for language learning as an effective cognitive intervention for aging populations. We propose that with sufficient engagement, language learning can enhance specific domains of cognition such as the executive functions. These results extend the understanding of cognitive reserve and its augmentation through targeted interventions, setting a foundation for future investigations.

neuroscience↗

bioRxiv2023

Concussion-related disruptions to hub connectivity in the default mode network are related to symptoms and cognition

Concussions present with a myriad of symptomatic and cognitive concerns; however, the relationship between these functional disruptions and the underlying changes in the brain are not yet well understood. Hubs, or brain regions that are connected to many different functional networks, may be specifically disrupted after concussion. Given the implications in concussion research, we quantified hub disruption within the default mode network (DMN) and between the DMN and other brain networks. We collected resting-state functional magnetic resonance imaging data from collegiate student-athletes (n = 44) at three timepoints: baseline (prior to beginning their athletic season), acute post-injury (approximately 48 hours after a diagnosed concussion), and recovery (after starting return-to-play progression, but prior to returning to contact). We used self-reported symptoms and computerized cognitive assessments collected across similar timepoints to link these functional connectivity changes to clinical outcomes. Concussion resulted in increased connectivity between regions within the DMN compared to baseline and recovery, and this post-injury connectivity was more positively related to symptoms and more negatively related to visual memory performance compared to baseline and recovery. Further, concussion led to decreased connectivity between DMN hubs and visual network non-hubs relative to baseline and recovery, and this post-injury connectivity was more negatively related to somatic symptoms and more positively related to visual memory performance compared to baseline and recovery. Relationships between functional connectivity, symptoms, and cognition were not significantly different at baseline versus recovery. These results highlight a unique relationship between self-reported symptoms, visual memory performance and acute functional connectivity changes involving DMN hubs after concussion in athletes. This may provide evidence for a disrupted balance of within- and between-network communication highlighting possible network inefficiencies after concussion. These results aid in our understanding of the pathophysiological disruptions after concussion and inform our understanding of the associations between disruptions in brain connectivity and specific clinical presentations acutely post-injury.

neuroscience↗

bioRxiv2023

Quantitative analyses of interactions between SpoVG and RNA/DNA

1.The Borrelia burgdorferi SpoVG protein has previously been found to be a DNA- and RNA-binding protein. To aid in the elucidation of ligand motifs, affinities for numerous RNAs, ssDNAs, and dsDNAs were measured and compared. The loci used in the study were spoVG, glpFKD, erpAB, bb0242, flaB, and ospAB, with particular focus on the untranslated 5 portion of the mRNAs. Performing binding and competition assays yielded that the 5 end of spoVG mRNA had the highest affinity while the lowest observed affinity was to the 5 end of flaB mRNA. Mutagenesis studies of spoVG RNA and ssDNA sequences suggested that the formation of SpoVG-nucleic acid complexes are not entirely dependent on either sequence or structure. Additionally, exchanging uracil for thymine in ssDNAs did not affect protein-nucleic acid complex formation.

microbiology↗