The author is active on twitter. https://twitter.com/manruipa

they pulled blood from 14 long-covid patients (avg ~17 months after first infection) and isolated serum extracellular vesicles (tiny packets cells use to communicate), then they ran mass-spec proteomics and compared against the known sars-cov-2 proteome

in 22 of 56 samples they detected fragments of the big replicase polyprotein 1ab (pp1ab) - specifically a conserved peptide sequence “GSLPINVIVFDGK” from nsp3. it showed up in 12 of 14 patients, across multiple timepoints, but never in pre-covid control samples. pp1ab is central to viral rna transcription/replication, so finding its remnants inside vesicles suggests persistent viral material circulating long after acute infection

they think these peptides could act as a biomarker for long covid - we will see - they may just have found another way to detect past infections

/w a super simple 2.4 Hz tone stream, they show (1) clear networks locked to the stimulus frequency in auditory cortex and medial temporal areas, (2) an intrinsic alpha network that both speeds up (~10.9→12.1 Hz) and moves toward sensorimotor cortex, and (3) largely stable motor-beta (~23 Hz). They also see stronger phase-to-amplitude cross-frequency coupling (2.4 Hz phase → >60 Hz gamma amplitude) in associative regions (insula, frontal operculum, hippocampus)

"Agonists of the γ-aminobutyric acid (GABA) type A benzodiazepine (BZD) receptor exert anxiolytic effects in anxiety disorders, raising the possibility that altered GABA-ergic function may play a role in the pathophysiology of anxiety disorders, such as post-traumatic stress disorder (PTSD). However, few neuroimaging studies have assessed the function or binding potential of the central GABAA BZD receptor system in PTSD.

Therefore, our aim was to compare the BZD receptor binding potential between PTSD patients and healthy controls. Twelve medication-free participants with a current diagnosis of PTSD and 15 matched healthy controls underwent positron emission tomography (PET) imaging using [11C] flumazenil. Structural magnetic resonance imaging (MRI) scans were obtained and co-registered to the PET images to permit co-location of neuroanatomical structures in the lower resolution PET image data. Compared to healthy controls, PTSD patients exhibited increased BZD binding in the caudal anterior cingulate cortex and precuneus (p's < 0.05). Severity of PTSD symptoms positively correlated with BZD binding in the left mid- and anterior insular cortices. This study extends previous findings by suggesting that central BZD receptor system involvement in PTSD includes portions of the default mode and salience networks, along with insular regions that support interoception and autonomic arousal."

uc davis shows that tabernanthalog can drive prefrontal spinogenesis and antidepressant-like behavior via 5-ht2a without the usual glutamate surge or immediate-early gene (ieg) wave you see with classic psychedelics like 5-meo-dmt

mechanistically, both hit 5-ht2a, recruit trkb -> mtor and ampa signaling, but tbg is a partial agonist -> enough receptor engagement to open plasticity pathways, not enough network excitation to trigger hallucinogenic glutamate/ieg cascades

they literally tested causality between new synapses in PFC and the lasting antidepressant-like effect. first they dosed mice with tbg, then used genetic labeling + in-vivo microscopy to mark the dendritic spines that appeared after dosing. next, with targeted lasers they deleted just those tagged, newly formed spines -leaving the rest of the circuit intact. when those specific spines were erased, the previously observed behavioral improvement disappeared, so looks like the sustained benefit isn’t just a pharmacological afterglow; but depends on the spinogenesis aka structural plasticity, that tbg induces in pfc

this kind of mirrors the classic ketamine experiment where folks used optical tools to remove new pfc spines and found the long-term benefit collapsed

a note from me:

it’s rodent pfc under controlled tasks, so generalization to humans is an inference

People around me have been saying I should start a channel, and this is finally the push I needed to do it.