Biology subjects

Reber, J.

Publications and source records attributed to Reber, J..

6 recordsLinked to original sources

bioRxiv2025

Load-dependent RGD-context sensing via αV-class integrins reprograms cellular adhesion and mechanics within seconds

The cellular ability to biophysically and biochemically recognize extracellular matrix proteins is fundamental to adhesion, mechanics, migration, and morphogenesis, and influences homeostasis and disease. However, the mechanisms underlying integrin-mediated mechanosensing of the arginine-glycine-aspartic acid (RGD)-motif of vitronectin and fibronectin remain elusive. Here, we discover that within seconds of sensing vitronectin, V-class integrins initiate and strengthen adhesion biphasically through complementary mechanotransduction pathways, which rely on the catch bond behavior of single V{beta}3 integrins. The first adhesion phase requires V{beta}3 and V{beta}5 integrin-associated actomyosin and FAK activity, while V{beta}5 integrin additionally requires clathrin-mediated endocytosis. With elevating mechanical load, the second phase requires V{beta}3 integrin-directed Arp2/3, cSrc, and PI3K signaling that dominates V{beta}5 integrin in organizing the consensus adhesome on vitronectin. Simultaneously, V{beta}5 integrin regulates the mechanical stiffening of fibroblasts. Thus, V-class integrins exhibit rapid RGD-motif- and {beta}-subunit-specific programs to synergistically guide mammalian cell adhesion and mechanics upon encountering diverse extracellular environments.

biophysics↗

bioRxiv2025

Precision Neuromodulation with Real-Time Brain Decoding for Working Memory Enhancement

Transcranial magnetic stimulation (TMS) has transformed non-invasive brain therapies but faces challenges due to variability in outcomes, likely stemming from inter-individual differences in brain function. This study aimed to address this challenge by integrating personalized functional networks (PFNs) derived from functional magnetic resonance imaging (fMRI) with a neural network-based decoder to optimize stimulation in real time during a working memory (WM) task. After identification of individualized stimulation targets, participants completed a TMS/fMRI session, performing a WM task while receiving rTMS at randomized frequencies. Decoder outputs and behavioral data during this session guided selection of optimal and suboptimal stimulation frequencies. Participants then underwent six stimulation sessions (three optimal, three suboptimal) in a randomized crossover design, performing WM and control tasks. The optimal stimulation improved WM performance by the final session, with no improvement observed in the control task. Additionally, the decoder output predicted behavioral performance on the WM task, both during the TMS/fMRI and neuromodulation sessions. These findings show that neural network-guided closed-loop neuromodulation can improve TMS effectiveness, marking a step forward in personalized brain stimulation. HIGHLIGHTSO_LIClosed-loop TMS guided by real-time brain decoding enhances post-stimulation behavioral effects. C_LIO_LIIndividualized functional connectivity networks enable targeted neuromodulation C_LIO_LIOptimal stimulation boosted working memory performance over sub-optimal C_LIO_LIBrain decoder readouts predicted behavioral performance C_LI

neuroscience↗

bioRxiv2022

Resting fMRI-guided TMS evokes subgenual anterior cingulate response in depression

Depression alleviation following treatment with repetitive transcranial magnetic stimulation (rTMS) tends to be more effective when TMS is targeted to cortical areas with high resting state functional connectivity (rsFC) with the subgenual anterior cingulate cortex (sgACC). However, it has not yet been confirmed that rsFC-guided TMS coil placement leads to TMS modulation of the sgACC. For each participant (N=115, 34 depressed patients), a peak rsFC cortical hotspot for the sgACC and control targets were prospectively identified. Single pulses of TMS interleaved with fMRI readouts were then administered to these targets and established significant downstream fMRI BOLD responses in the sgACC. We then marked an association between TMS-evoked BOLD responses in the sgACC and rsFC between the stimulation site and sgACC. This effect was qualified by a difference between healthy and patient participants: only in depressed patients, positively connected sites of stimulation led to the strongest evoked responses in the sgACC. Our results highlight rsFC-based targeting as a viable strategy to causally modulate sgACC subcortical targets and further suggest that cortical sites with high positive rsFC to the sgACC might represent an alternative target for the treatment of depression.

neuroscience↗

bioRxiv2019

Advances in Spiral fMRI: A High-resolution Study with Single-shot Acquisition

Spiral fMRI has been put forward as a viable alternative to rectilinear echo-planar imaging, in particular due to its enhanced average k-space speed and thus high acquisition efficiency. This renders spirals attractive for contemporary fMRI applications that require high spatiotemporal resolution, such as laminar or columnar fMRI. However, in practice, spiral fMRI is typically hampered by its reduced robustness and ensuing blurring artifacts, which arise from imperfections in both static and dynamic magnetic fields. Recently, these limitations have been overcome by the concerted application of an expanded signal model that accounts for such field imperfections, and its inversion by iterative image reconstruction. In the challenging ultra-high field environment of 7 Tesla, where field inhomogeneity effects are aggravated, both multi-shot and single-shot 2D spiral imaging at sub-millimeter resolution was demonstrated with high depiction quality and anatomical congruency. In this work, we further these advances towards a time series application of spiral readouts, namely, single-shot spiral BOLD fMRI at 0.8 mm in-plane resolution. We demonstrate that high-resolution spiral fMRI at 7 T is not only feasible, but delivers both excellent image quality, BOLD sensitivity, and spatial specificity of the activation maps, with little artifactual blurring. Furthermore, we show the versatility of the approach with a combined in/out spiral readout at a more typical resolution (1.5 mm), where the high acquisition efficiency allows to acquire two images per shot for improved sensitivity by echo combination. HighlightsO_LIThis work reports the first fMRI study at 7T with high-resolution spiral readout gradient waveforms. C_LIO_LIWe achieve spiral fMRI with sub-millimeter resolution (0.8 mm, FOV 230 mm), acquired in a single shot (36 slices in 3.3 s). C_LIO_LISpiral images exhibit intrinsic geometric congruency to anatomical scans, and spatially specific activation patterns. C_LIO_LIImage reconstruction rests on a signal model expanded by measured trajectories and static field maps, inverted by cg-SENSE. C_LIO_LIWe assess generalizability of the approach for spiral in/out readouts, providing two images per shot (1.5 mm resolution). C_LI

neuroscience↗

bioRxiv2019

Beyond early development: observing zebrafish over 6 weeks with hybrid optical and optoacoustic imaging

Zebrafish animal models have traditionally been used in developmental biology studies but have recently become promising models of cancer, tissue regeneration and metabolic disorders, as well as efficient platforms for functional genomics and phenotype-based drug discovery. Most studies of zebrafish have examined only the embryonic or larval stages of development, yet many questions in developmental biology and biomedicine require analysis of adults, when zebrafish are large and opaque. Conventional microscopy methods are highly sensitive to light scattering and therefore cannot be applied to zebrafish older than a few weeks. We describe a novel multi-modality system that can observe zebrafish from the larval stage to adulthood. Using a hybrid platform for concurrent selective plane illumination microscopy (SPIM) and optoacoustic mesoscopy we show continuous imaging of fish growth over 47 days of development at a similar object size-to-resolution ratio. Using multiple wavelength illumination over the visible and short-wavelength infrared regions, we reveal that the optoacoustic method can follow GFP-based contrast used in SPIM, enabling molecular imaging interrogation in adult fish. Moreover we optoacoustically reveal many other features of zebrafish based on optical contrast not present in SPIM, including contrast from endogenous blood, water and lipids. The hybrid method presented can extend optical imaging to adult zebrafish employed as model systems for studying long-term processes in development, cancer, diabetes and other disorders.

biophysics↗

bioRxiv2018

Mid-infrared optoacoustic microscopy with label-free chemical contrast in living cells and tissues

We developed mid-infrared optoacoustic microscopy (MiROM), a bond-selective imaging modality that overcomes water/tissue opacity and depth limitations of mid-infrared sensing allowing uncompromised live-cell/thick-tissue mid-infrared microscopy with up to three orders of magnitudehigher sensitivity than other vibrational imaging modalities; such as Raman. We showcase the functional label-free biomolecular imaging capabilities of MiROM by monitoring the spatiotemporal dynamics of lipids and proteins during lipolysis in living adipocytes. Since MiROM, contrary to Ramanmodalities, is not only able to detect lipids and proteins, but also important metabolites such as glucose without the need of labels, here we discuss how MiROM yields novel functional label-free abilities for a broader range of analytical studies in living cells and tissues.

cell biology↗