Biology subjects

Boos, A.

Publications and source records attributed to Boos, A..

7 recordsLinked to original sources

bioRxiv2026

MAFA drives pancreatic islet maturation through coordination of cell growth, metabolic maturation, and resilience to stress.

Stem cell-derived islets (SC-islets) are a promising source for replacing the loss of insulin-secreting {beta} cells in insulin-dependent diabetes patients, but compared to their primary human counter parts, SC-islets are considered functionally immature and do not immediately regulate blood glucose after transplantation. To better understand the molecular underpinnings of {beta} cell maturation, we genetically engineered human pluripotent stem cells (hPSCs) to control the induction of the {beta} cell-maturing transcription factor MAFA or a MAFA S64F mutant variant associated with premature {beta} cell aging and senescence in SC-islets. We employ a combination of in vitro assays, multi-omics analyses, and murine in vivo transplantation studies to demonstrate that MAFA remodeling of the SC-islet transcriptional landscape promotes SC-islet biogenesis and metabolic maturation giving rise to greater SC-islet resilience and insulin secretory capacity. Parallel MAFA S64F studies highlight the importance for compensatory mechanisms for sustaining accelerated oxidative metabolism and enhanced insulin secretion without inducing intracellular stress responses and islet dysfunction. Overall, these results reveal MAFA-governed transcriptional changes that drive SC-islet functional maturation, which provides the foundation for maturing SC-islets in vitro, preserving {beta} cell integrity, and improving SC-islet cell replacement therapies.

cell biology↗

bioRxiv2026

Cervical spinal cord stimulation disrupts proprioception yet improves voluntary arm reaching

Whether proprioception is necessary for upper-limb motor control has been debated for decades. Classic studies in deafferented animals and humans suggested that proprioception may be dispensable for rapid, goal-directed movements. However, chronic sensory loss conflates the absence of proprioceptive input with years of compensatory adaptation. As a result, the field has lacked a strong causal test of proprioceptions contribution to motor control. Here, we leveraged a clinical trial of cervical spinal cord stimulation (SCS) in individuals with chronic post-stroke hemiparesis to study if electrical stimulation of sensory afferents causally perturbs proprioception and affects arm reaching. We found that turning SCS ON causally impaired proprioceptive perception and postural stabilization in response to force perturbations, and enhanced adaptation to visual errors during implicit learning. Yet visually and non-visually rapid, goal-directed reaching improved in smoothness, straightness and spatial accuracy. These findings provide strong causal evidence that proprioception is not required for rapid, goal-directed action, helping resolve a decades-long debate regarding its necessity for effective movement.

bioengineering↗

bioRxiv2026

Enabling Skilled Human-Computer Interaction After Paralysis via a Wearable sEMG Interface

Most individuals with tetraplegia retain some myoelectric function in their forearms, which offers the possibility of using surface electromyographic (sEMG) control for human-computer interaction (HCI). We demonstrate the potential of this approach by showing that people with motor-complete (n=5) and motor-incomplete (n=2) tetraplegia can accurately control myoelectric activity in their forearm to perform discrete button-click and continuous positioning tasks. These control inputs were mapped to the firing rate of motor units detected by a wireless wristband sensor designed for everyday use. Participants completed four testing sessions to assess their speed and accuracy. Motor units that displayed a wide dynamic range in their firing rate performed best during tasks requiring continuous, single-axis control. Interestingly, the level of impairment did not affect performance on the clicking and 1D cursor control tasks. However, those with motor-incomplete injuries showed greater independent control over two motor units than participants with motor-complete injuries, who exhibited stronger coupling between units. Participants also confirmed the practical utility of the device, successfully placing and removing the sEMG wristband on their own and consistently rating it as comfortable and easy to manage. These findings are significant because they offer the first demonstration of motor unit-based control in individuals with cervical spinal cord injury (SCI) using a fully wearable wristband interface, highlighting the feasibility of moving these systems out of the lab and into daily life. One-Sentence SummaryPeople with tetraplegia used a wristband sensor to detect forearm motor unit firing and perform human-computer interaction tasks.

bioengineering↗

bioRxiv2025

Mapping the Causal Roles of Non-Primary Motor Areas in Human Reach Planning and Execution

Non-primary motor areas, including the dorsal premotor cortex (PMd), ventral premotor cortex (PMv), and posterior parietal cortex (PPC), are involved in movement planning, but their precise contributions remain unclear. We used functional magnetic resonance imaging (fMRI), transcranial magnetic stimulation (TMS), and kinematic assessments to explore how these areas influence reaching performance in neurologically intact adults. Participants performed a reaching task using the KINARM exoskeleton robot. Brief TMS pulse trains were initiated before movement onset to perturb cortical activity at subthreshold and suprathreshold intensities targeting bilateral PMd, PMv, and PPC. Subthreshold stimulation of contralateral PMd and PMv reduced reach efficiency and smoothness, while suprathreshold stimulation of contralateral PPC increased deviation error and reduced smoothness. Among ipsilateral targets, PMd showed consistent TMS-induced effects, and was the only target where resting-state connectivity predicted behavioral response. Stronger interhemispheric connectivity in the primary motor cortex and weaker interhemispheric PPC connectivity were associated with greater reductions in straightness and smoothness during subthreshold ipsilateral PMd stimulation. These findings show that perturbation of premotor and parietal areas during early movement execution alters reach trajectories, and differences in network organization explain variability in behavioral response. Identifying contributions of cortical areas and connectivity patterns may help personalize interventions after stroke. This study was registered at ClinicalTrials.gov under ID NCT04286516.

bioengineering↗

bioRxiv2023

Understanding Age-Related Changes in Proprioception through Active and Passive Tasks

Voluntary control of motor actions requires precise regulation of proprioceptive and somatosensory functions. While aging has demonstrated to decline sensory processing functions, the effect of age on proprioception remains less clear. Indeed, previous studies contradict on whether passive proprioception (i.e., during externally driven movements) is affected over age. Moreover, no studies explored age-related modifications in active proprioception (i.e., during voluntary movements). Understanding these changes is critical to identify and prevent possible causes of reduced movement performances and mobility, in particular in age-related neurological conditions such as stroke or Parkinson disease. Here, we first refined a robotic protocol to assess upper-limb active proprioception and demonstrated the robustness and reliability of outcome measures over sessions. We then compared performances between young and elderly subjects during active and passive proprioceptive tasks. We found that while the two populations of subjects performed similarly in passive proprioception, elderly subjects acuity declined during active proprioception. Importantly, we confirmed that the decline could not be explained by impairments in voluntary motor control. Our data and robotic protocols further elucidate the debate over proprioception in elderly subjects and provide evidence that robust proprioceptive assessments should be an essential measurement in clinical settings. New & NoteworthyUpper limb position sense has been previously evaluated using passive matching protocols with the contralateral arm. These studies have found contradicting results regarding a possible decline in passive proprioception over age. Here we replicated this passive protocol and compared it to its active counterpart. Our results suggest that aging has an effect only in the active condition, leading to the hypothesis of a potential role of the cortico-spinal and cerebellar pathways in proprioception decline.

bioengineering↗

bioRxiv2020

Electrophysiological investigation of reward anticipation and outcome evaluation during slot machine play

Slot machines are a popular form of gambling, offering a tractable way to experimentally model reward processes. This study used a 3-reel slot paradigm to assess psychologically distinct phases of reward processing, reflecting anticipation, and early and late-stage outcome processing. EEG measures of winning, nearly missing (a losing outcome revealed at the final, third reel), and "totally" missing (a losing outcome revealed earlier, at the second reel) were collected from healthy adults (n=54). Condition effects were evaluated in: i) event-related potential (ERP) components reflecting anticipatory attention (stimulus preceding negativity, SPN) and outcome processing (reward positivity, RewP and late-positive potential, LPP) and ii) total power and phase synchrony of theta and delta band oscillations. Behaviorally, trial initiation was fastest after a near miss outcome and slowest after a winning outcome. As expected, a significant SPN was observed for possible wins (AA) vs. total misses (AB), consistent with reward anticipation. In addition, significantly larger win (AAA) vs. near miss (AAB) amplitudes were observed for the RewP and LPP to wins and LPP to near misses (vs. total misses) reflecting early and late-stage outcome processing effects. There was an effect of reel position on the RewP, with larger effects in the final reel (AAA-AAB) relative to the 2nd-reel locked difference waves (AA-AB). Across all outcomes, near misses elicited the largest and most phase-synchronized theta responses, while wins elicited larger and more phase-synchronized delta responses than total misses, with near misses not differing from wins or total misses. Phase locking measures contrasting win vs. near miss delta and theta synchronization, within time windows corresponding to ERP measurements, covaried with RewP, but not SPN or LPP, amplitude. Lastly, EEG measures showed differential relationships with age and self-reported consummatory pleasure. In the context of slot machine play, where reward anticipation and attainment place minimal demands on effort and skill, ERP and time-frequency methods capture distinct neurophysiological signatures of reward anticipation and outcome processing.

neuroscience↗

bioRxiv2018

A re-inducible genetic cascade patterns the anterior-posterior axis of insects in a threshold-free fashion

Gap genes mediate the division of the anterior-posterior axis of insects into different fates through regulating downstream hox genes. Decades of tinkering the segmentation gene network of the long-germ fruit fly Drosophila melanogaster led to the conclusion that gap genes are regulated (at least initially) through a threshold-based French Flag model, guided by both anteriorly- and posteriorly-localized morphogen gradients. In this paper, we show that the expression patterns of gap genes in the intermediate-germ beetle Tribolium castaneum are mediated by a threshold-free Speed Regulation mechanism, in which the speed of a genetic cascade of gap genes is regulated by a posterior gradient of the transcription factor Caudal. We show this by re-inducing the leading gap gene (namely, hunchback) resulting in the re-induction of the gap gene cascade at arbitrary points in time. This demonstrates that the gap gene network is self-regulatory and is primarily under the control of a posterior speed regulator in Tribolium and possibly all insects.

developmental biology↗