Biology subjects

Jung, R.

Publications and source records attributed to Jung, R..

9 recordsLinked to original sources

bioRxiv2026

Selective Activation of Nerve Fiber Subpopulations with Intrafascicular Stimulation

BackgroundPeripheral nerve stimulation (PNS) is most effective when specific nerve fiber subpopulations are activated, while minimizing off-target activation, which may cause undesirable side effects. This selectivity depends primarily on electrode design and charge delivery. We hypothesized that selective PNS could be achieved through electrode placement and intrafascicular electric field steering using Longitudinal Intrafascicular Electrodes (LIFEs). MethodsLIFEs were implanted into the tibial fascicle of the sciatic nerve of 17 anesthetized adult rats. We tested whether electrodes positioned at different cross-sectional and longitudinal locations within the same fascicle, together with different electric field-steering approaches produced distinct activation patterns in the gastrocnemius lateralis muscle. Muscle responses were measured using high-density epimysial electromyography (HD-eEMG). ResultsElectrodes placed at different locations within the same fascicle activated distinct muscle regions, demonstrating intrafascicular selectivity. Bipolar stimulation recruited nerve fibers differently than monopolar stimulation, showing that electric field steering can further shape the selective recruitment. In both configurations, increasing the stimulation amplitude produced a graded increase in muscle activation. Furthermore, our findings demonstrated that HD-eEMG is an effective tool for evaluating intrafascicular selectivity. ConclusionThese findings suggest that improving on-target selectivity may support next-generation bioelectronic therapies with better outcomes and fewer side effects, potentially enabling more precise, organ-specific neuromodulation. Using multiple intrafascicular electrodes may provide two complementary strategies for enhancing selectivity: strategic intrafascicular placement to access different fiber subpopulations and bipolar configurations to steer recruitment beyond what a single electrode can achieve.

bioengineering↗

bioRxiv2025

Rapid enrichment of progenitor exhausted neoantigen-specific CD8 T cells from peripheral blood

Neoantigen-reactive peripheral blood lymphocytes (NeoPBL) are tumor-specific T cells found at ultra-low frequencies in the blood. Unlike tumor-infiltrating lymphocytes (TIL), NeoPBL exist in a favorable less dysfunctional phenotypic state in vivo, but their rarity has precluded their effective use as cell therapy. Leveraging a priori knowledge of bona fide neoantigens, we combined high-intensity neoantigen stimulation with bead extraction of neoantigen peptide-pulsed target cells to enable the enrichment of NeoPBL to frequencies comparable to ex vivo cultured TIL over a 28-day period. Throughout this process, NeoPBL demonstrate specific reactivity against autologous tumor organoids and maintain memory-like features, including elevated expression of CD28 and TCF7. We additionally demonstrate that NeoPBL reactivity is polyclonal, encompassing multiple clonotypes that are detectable within in vivo TIL populations, underscoring physiological specificity for the targeted neoantigens. This streamlined process yields clinically relevant cell doses and enables identification and expansion of blood-derived neoantigen-specific TCRs. By potentially avoiding additional surgical risks and protracted delays of TIL and individualized TCR-engineered methods, the NeoPBL platform may have clinical and practical advantages. Ultimately, NeoPBL combines intrinsic cell fitness, minimal invasiveness and rapidity to potentially facilitate personalized adoptive cell therapy for cancer.

immunology↗

bioRxiv2025

Decoding the Human Brain during Intelligence Testing

Understanding the brain mechanisms underlying complex human cognition is a major objective in neuroscience. Previous studies have identified neural correlates of intelligence at different temporal and spatial scales using functional magnetic resonance imaging (fMRI) and electroencephalography (EEG) separately. This study treats intelligence as a multilayer phenomenon across temporal and spatial scales and examines how the connectedness of brain regions as well as the complexity of multilayer brain dynamics relates to performance in an established intelligence test. Graph-theoretical analyses of fMRI-derived functional connectivity (N=67) revealed that the connectedness of frontal and parietal regions was associated with individual performance. Further, multiscale entropy analyses of EEG signals (N=131) disclosed that higher test scores were linked to more complex long-range processes and, at a trend level, to less complex short-range processes. These findings support the Multilayer Processing Theory, proposing the interplay between flexible long-range and modular short-range processes as the neural bases of intelligence.

neuroscience↗

bioRxiv2021

A low-resource reliable pipeline to democratize multi-modal connectome estimation and analysis

Connectomics--the study of brain networks--provides a unique and valuable opportunity to study the brain. Research in human connectomics, leveraging functional and diffusion Magnetic Resonance Imaging (MRI), is a resource-intensive practice. Typical analysis routines require significant computational capabilities and subject matter expertise. Establishing a pipeline that is low-resource, easy to use, and off-the-shelf (can be applied across multifarious datasets without parameter tuning to reliably estimate plausible connectomes), would significantly lower the barrier to entry into connectomics, thereby democratizing the field by empowering a more diverse and inclusive community of connectomists. We therefore introduce MRI to Graphs (m2g). To illustrate its properties, we used m2g to process MRI data from 35 different studies ({approx} 6,000 scans) from 15 sites without any manual intervention or parameter tuning. Every single scan yielded an estimated connectome that adhered to established properties, such as stronger ipsilateral than contralateral connections in structural connectomes, and stronger homotopic than heterotopic correlations in functional connectomes. Moreover, the connectomes estimated by m2g are more similar within individuals than between them, suggesting that m2g preserves biological variability. m2g is portable, and can run on a single CPU with 16 GB of RAM in less than a couple hours, or be deployed on the cloud using its docker container. All code is available on https://github.com/neurodata/m2g and documentation is available on docs.neurodata.io/m2g.

bioinformatics↗

bioRxiv2021

Engaging Biological Oscillators through Second Messenger Pathways Permits Emergence of a Robust Gastric Slow-Wave during Peristalsis

Peristalsis, the coordinated contraction - relaxation of the muscles of the stomach is important for normal gastric motility and is impaired in motility disorders. Coordinated electrical depolarizations that originate and propagate within a network of interconnected layers of interstitial cells of Cajal (ICC) and smooth muscle (SM) cells of the stomach wall as a slow-wave, underly peristalsis. Normally, the gastric slow-wave oscillates with a single period and uniform rostrocaudal lag, exhibiting network entrainment. Understanding of the integrative role of neurotransmission and intercellular coupling in the propagation of an entrained gastric slow-wave, important for understanding motility disorders, however, remains incomplete. Using a computational framework constituted of a novel gastric motility network (GMN) model we address the hypothesis that engaging biological oscillators (i.e., ICCs) by constitutive gap junction coupling mechanisms and enteric neural stimulus activated signals can confer a robust entrained gastric slow-wave. We demonstrate that while a decreasing enteric neural stimulus gradient that modulates the intracellular IP3 concentration in the ICCs can guide the aboral slow-wave propagation essential for peristalsis, engaging ICCs by recruiting the exchange of second messengers (inositol trisphosphate (IP3) and Ca2+) ensures a robust entrained longitudinal slow-wave, even in the presence of biological variability in coupling strengths. Our GMN with the distinct intercellular coupling in conjunction with the intracellular feedback pathways and a rostrocaudal enteric neural stimulus gradient allows gastric slow waves to oscillate with a moderate range of frequencies and to propagate with a broad range of velocities, thus preventing decoupling observed in motility disorders. Overall, the findings provide a mechanistic explanation for the emergence of decoupled slow waves associated with motility impairments of the stomach, offer directions for future experiments and theoretical work, and can potentially aid in the design of new interventional pharmacological and neuromodulation device treatments for addressing gastric motility disorders. Author SummaryThe coordinated contraction and relaxation of the muscles of the stomach, known as peristalsis is important for normal gastric motility and primarily governed by electrical depolarizations that originate and propagate within a network of interconnected layers of interstitial cells of Cajal (ICCs) and smooth muscle cells of the stomach wall as a slow-wave. Under normal conditions, a gastric slow-wave oscillates with a single period and uniform rostrocaudal lag, exhibiting network entrainment. However, the understanding of intrinsic and extrinsic mechanisms that ensure propagation of a robust entrained slow-wave remains incomplete. Here, using a computational framework, we show that in conjunction with an enteric neural stimulus gradient along the rostrocaudal ICC chain, and intercellular electrical coupling, the intercellular exchange of inositol trisphosphate between ICCs prevents decoupling by extending the longitudinal entrainment range along the stomach wall, even when variability in intercellular coupling exists. The findings from our study indicate ways that ensure the rostrocaudal spread of a robust gastric slow-wave and provide a mechanistic explanation for the emergence of decoupled slow waves associated with motility impairments of the stomach.

neuroscience↗

bioRxiv2020

Tissue-specific safety mechanism results in opposite protein aggregation patterns during aging

During aging, proteostasis capacity declines and aggregation-prone proteins become instable, accumulating in protein aggregates both inside and outside cells. Both in disease and during aging, proteins selectively aggregate in certain tissues and not others. Yet, tissue-specific regulation of protein aggregation remains poorly understood. Surprisingly, we found that the inhibition of three core protein quality control systems, i.e. chaperones, proteasome and macroautophagy, leads to lower levels of age-dependent protein aggregation in C. elegans pharyngeal muscles, but higher levels in body-wall muscles. We describe a novel safety mechanism called SAPA that selectively targets newly synthesized aggregation-prone proteins to suppress aggregation and proteotoxicity. vha-12 and scav-3 mutants reveal that SAPA relies on macroautophagy-independent lysosomal degradation. Furthermore, SAPA involves several previously uncharacterized components of the intracellular pathogen response. We propose that SAPA represents an anti-aggregation machinery targeting aggregation-prone proteins for lysosomal degradation.

cell biology↗

bioRxiv2019

The polyQ expansion modulates the configuration and phosphorylation of huntingtin

The polyQ-expansion at the N-terminus of huntingtin (HTT) is the prime cause of Huntingtons disease. The recent cryo-EM structure of HTT with HAP40 provides information on the proteins prominent HEAT-repeats. Here, we present analyses of the impact of polyQ-length on the conformation of HTT by cryo-EM, the domain-interactions by cross-linking mass spectrometry and the phosphorylation of HTT. The cryo-EM analysis of normal (Q23-) and disease (Q78-) type HTTs in their apo forms shows that the structures of apo HTTs significantly differ from the structure of HTT-HAP40, and that the polyQ expansion induces global structural changes consisting of significant domain movements of the C-HEAT domain relative to the N-HEAT domain. In addition, we show that the polyQ-expansion alters the phosphorylation pattern across the full-length HTT and that the specific phosphorylation (Ser2116p) in turn affects the global structure of HTT, which influences the activity of polyQ-expanded HTT. These results provide a molecular basis for the effect of the N-terminal polyQ segment on HTT structure and activity, that may be important for the cell-selective toxicity of mutant HTT.

neuroscience↗

bioRxiv2018

Restoring ventilatory control using an adaptive bioelectronic system

Key Points SummaryO_LIElectrical stimulation of the diaphragm muscle or phrenic nerve, or ventilatory pacing, serves as an alternative to mechanical ventilation.\nC_LIO_LICurrently available ventilatory pacing systems are open-loop, requiring long set-up sessions and frequent tuning.\nC_LIO_LIA neuromorphic closed-loop bioelectronic controller capable of autonomously adapting current amplitude to achieve a desired breath volume profile has been developed.\nC_LIO_LIThe controller was able to achieve a desired volume profile in intact animals and restore tidal volume to values observed prior to injury in spinal cord hemisected animals.\nC_LIO_LIThis controller architecture allows for ventilatory pacing that requires minimal technician input during setup and constantly adapts to account for changes such as those induced by muscle fatigue.\nC_LIO_LIThe adaptive control system could be used as a respiratory rehabilitation tool to strengthen inspiratory muscles and for automated weaning from mechanical ventilation.\nC_LI\n\nAbstractVentilatory pacing via electrical stimulation of the phrenic nerve or of the diaphragm has been shown to enhance quality of life compared to mechanical ventilation. However, commercially-available ventilatory pacing devices require initial manual specification of stimulation parameters and frequent adjustment to achieve and maintain suitable ventilation over long periods of time. Here, we have developed an adaptive, closed-loop, neuromorphic, pattern-shaping controller capable of automatically determining a suitable stimulation pattern and adapting it to maintain a desired breath volume profile on a breath-by-breath basis. In vivo studies in anesthetized intact and C2-hemisected male Sprague-Dawley rats indicated that the controller was capable of automatically adapting stimulation parameters to attain a desired volume profile. Despite diaphragm hemiparesis, the controller was able to achieve a desired volume in the injured animals that did not differ from the tidal volume observed prior to injury (p=0.39). The closed-loop controller was developed and parametrized in a computational testbed prior to in-vivo assessment. This bioelectronic technology could serve as an individualized and autonomous respiratory pacing approach for support or recovery from ventilatory deficiency.

physiology↗

bioRxiv2018

Intrinsically aggregation-prone proteins form amyloid-like aggregates and contribute to tissue aging in C. elegans

Reduced protein homeostasis and increased protein instability is a common feature of aging. Yet it remains unclear whether protein instability is a cause of aging. In neurodegenerative diseases and amyloidoses, specific proteins self-assemble into amyloid fibrils and accumulate as pathological solid aggregates in a variety of tissues. More recently, widespread protein aggregation has been described during normal aging, in the absence of disease processes. Until now, an extensive characterization of the nature of age-dependent protein aggregation and its consequences for aging has been lacking. Here, we show that age-dependent aggregates are rapidly formed by newly synthesized proteins and contain amyloid-like structures similar to disease-associated protein aggregates. Moreover, we demonstrate that age-dependent protein aggregation accelerates the functional decline of different tissues in C. elegans. Together, these finding reveal that the formation of amyloid aggregates is a generic problem of aging and likely to be an important target for strategies designed to maintain physiological functions in later stages of life.

cell biology↗