Biology subjects

Allen, J. J.

Publications and source records attributed to Allen, J. J..

4 recordsLinked to original sources

bioRxiv2026

Facilitating Mindfulness Training with Ultrasonic Neuromodulation

Systematic focus training is increasingly recognized for its therapeutic benefits, with equanimity, the ability to maintain an open and accepting attitude towards all experience, identified as a critical mechanism for improving well-being. Physiologically, experienced meditators demonstrate reduced activity in the posterior cingulate cortex (PCC), a hub of the default mode network (DMN), and increased segregation between the DMN and the central executive network (CEN). This study investigated whether non-invasive neuromodulation could facilitate these neural and behavioral shifts in novice practitioners. We conducted a single-blind, randomized controlled trial with 24 meditation-naive participants who engaged in a two-week "Body Focus" mindfulness training program. Participants were randomized to receive either active (n=16) or sham (n=8) suppressive transcranial focused ultrasound (tFUS) targeting the PCC during four in-person meditation sessions. Resting-state fMRI analysis revealed a robust Condition x Session interaction in functional connectivity. While the sham group showed a trend toward increased coupling, the active tFUS group demonstrated significant decoupling (increased segregation) between the DMN and CEN, a pattern characteristic of advanced meditators. Subnetwork analysis indicated these effects were driven primarily by the decoupling of the core self-referential system in DMN (DMNA) from the external-oriented control system of the CEN (CENB). Behaviorally, greater reductions in DMN-CEN connectivity within the active group predicted larger increases in self-reported acceptance and longer duration of voluntary meditation practice. These findings suggest that tFUS targeting the PCC can acutely redirect neuroplastic trajectories during early mindfulness training, potentially accelerating the acquisition of equanimity and distinct network configurations associated with effortless awareness. Significance StatementThis study demonstrates that transcranial focused ultrasound (tFUS) targeting the posterior cingulate cortex (PCC) can synergistically enhance mindfulness training in novices. By inducing a robust decoupling between the default mode and central executive networks - a neural signature typically acquired only after hundreds of hours of practice - this intervention effectively redirected the neural trajectory of novice practitioners toward that of experienced meditators in just two weeks. These findings suggest that targeted neuromodulation can bypass early obstacles in meditation practice, offering a promising "precision wellness" avenue for accelerating the acquisition of equanimity and its associated well-being benefits.

neuroscience↗

bioRxiv2025

Selective Detection of a Key Region in Chemotaxis Signaling Protein Complexes by Solid-State NMR

Understanding how large protein complexes function requires tools that can resolve both structure and dynamics in their native assembly states. Here, we apply solid-state NMR (SSNMR) to selectively detect rigid regions of a receptor protein fragment in the context of the >500 kDa chemoreceptor signaling complex found in chemotactic bacteria. These complexes assemble into hexagonal arrays that network multiple active units together. The cytoplasmic fragment of the E. coli aspartate chemoreceptor exhibits dynamics on multiple timescales across different regions of the protein, and these dynamics differ between signaling states. We apply 13C-15N dipolar coupling-based SSNMR experiments to selectively probe the rigid portion (motions slower than millisecond timescale) of this protein, in the context of the full array structure. We optimized assembly methods to form native-like, homogeneous complexes capable of maintaining activity and sample integrity during extended NMR experiments with low electric-field NMR probe designs. A subset of the protein, approximately 100 residues at the membrane-distal tip of the chemoreceptor where it interacts with its associated kinase, was detected and identified as the most rigid region. Chemical shift changes for many residues in this rigid region were observed between NMR spectra of the kinase-on and kinase-off signaling states. This suggests conformational changes occur at the chemoreceptor tip during signaling, which have not been observed in previous studies of this system. These findings demonstrate a dynamics-based NMR spectral editing approach to selectively examine a key region of a large signaling protein within its macromolecular assembly. Statement of SignificanceLarge protein complexes are challenging to study, but understanding their mechanism is vital to gaining insight into many important biological processes. In this work we demonstrate the use of solid-state NMR to study such a system, bacterial chemotaxis receptor signaling complexes. We identified an in vitro assembly method that creates reproducible and durable complexes that retain activity for weeks of data collection. Selective NMR detection of a key region of one protein reveals significant differences between signaling states, indicating there are changes in conformation and dynamics that were not previously seen by cryo-electron tomography and crystallography of this system. This highlights the potential of solid-state NMR as a key tool in mechanistic studies of multi-protein complexes.

biochemistry↗

bioRxiv2020

Polymorphic SINEC_Cf Retrotransposons in the Genome of the Dog (Canis familiaris)

The dog is an exciting genetic system in which many simple and complex traits have now been mapped. For many traits the causal mutation is a polymorphic SINE. To investigate the genome-wide pattern of young SINEC_Cf insertions, we sampled 62 dogs representing 59 breeds and sequenced libraries enriched for SINE flanks. In each dog we detect an average of 10,423 polymorphic loci and all together the libraries identify 81,747 putative polymorphic SINEs. We validated 184 SINEs inserted in protein-coding exons, untranslated regions, introns and intergenic sequence. In dogs both SINEC_Cf and LINEs exhibit a strand bias in introns where antisense copies are more frequent. Antisense polymorphic SINEs also have a higher density in introns. Both SINEs and LINEs drop to very low density near exons. Both sense and antisense polymorphic SINEs also drop to low density upstream of coding exons but not downstream. Antisense polymorphic SINEC_Cfs upstream of coding exons are known to cause narcolepsy, merle, and progressive retinal atrophy in dogs. In other mammals SINE pairs in inverted orientation disrupt gene expression. We find inverted pairs of SINEC_Cf are rare in both introns and intergenic sequence when the two SINEs are separated by less than 100 bp. The lack of inverted pairs is even more pronounced when the SINEs have high sequence identity. Intronic and intergenic LINE pairs show similar patterns. Polymorphic SINEs rarely pair with either SINEC_Cf or SINEC_Cf2. Overall, the high insertion rate of SINEC_Cf provides a natural mutagenesis screen in the dog genome.

genomics↗

bioRxiv2018

HIV-1 vaccine design through minimizing envelope metastability

Overcoming envelope metastability is crucial to trimer-based HIV-1 vaccine design. Here, we present a coherent vaccine strategy by minimizing metastability. For ten strains across five clades, we demonstrate that gp41 ectodomain (gp41ECTO) is the main source of envelope metastability by replacing wild-type gp41ECTO with BG505 gp41ECTO of the uncleaved prefusion-optimized (UFO) design. These gp41ECTO-swapped trimers can be produced in CHO cells with high yield and high purity. Crystal structure of a gp41ECTO-swapped trimer elucidates how a neutralization-resistant tier 3 virus evades antibody recognition of the V2 apex. UFO trimers of transmitted/founder (T/F) viruses and UFO trimers containing a consensus-based ancestral gp41ECTO suggest an evolutionary root of the metastability. Gp41ECTO-stabilized trimers can be readily displayed on 24- and 60-meric nanoparticles, with incorporation of additional T cell help illustrated for a hyperstable 60-mer. In mice and rabbits, gp140 nanoparticles induced more effective tier 2 neutralizing antibody response than trimers with statistical significance.\n\nHIGHLIGHTSO_LIgp41 is the main source of HIV-1 envelope metastability\nC_LIO_LIBG505 gp41 of the UFO design stabilizes gp140 trimers of diverse subtypes\nC_LIO_LIgp41 stabilization facilitates gp140 nanoparticle assembly and improves production\nC_LIO_LINanoparticles elicit tier 2 neutralizing antibodies more effectively than trimers\nC_LI

microbiology↗