Acupuncture at ST36 Alleviates the Behavioral Disorder of Autistic Rats by Inhibiting TXNIP-Mediated Activation of NLRP3

Autism is a common neurodevelopmental disorder that severely affects patients’ quality of life. We aimed to investigate whether acupuncture at Zusanli (ST36) could alleviate the behavior disorder of autistic rats by inhibiting thioredoxin-interacting protein (TXNIP)-mediated activation of NLRP3. An autism model was induced by intraperitoneal injection of pregnant rats with valproic acid (VPA). The pups’ behaviors were analyzed using hot plate, open field, Morris water maze, and 3-chamber social interaction tests. Nissl staining was used to visualize neurons in prefrontal cortex. Levels of TXNIP, NLRP3, interleukin (IL)-1β, and caspase were determined by Western blot or quantitative real-time PCR. After ST36 acupuncture, pain sensitivity, autonomous activity, sociability index, sociability preference index, and learning and memory were improved in the autism model rats. Levels of TXNIP, NLRP3, IL-1β, and caspase 1 were decreased after acupuncture. Interference with TXNIP alleviated the behavior disorders and inhibited NLRP3, caspase 1, and IL-1β levels. In summary, ST36 acupuncture reduced TXNIP expression, inhibited the activation of the NLRP3 inflammasome, and alleviated the behavior disorder related to the prefrontal cortex of the autistic rats. These results point to a potential mechanism for acupuncture-induced improvement of autistic behavioral disorders.

Cybersecurity Capacity Building

Some claim that cybersecurity capacity building has developed into a discrete specialism. But, if it has become a niche activity, it is one that nevertheless comes into contact with a wide array of policy areas, ranging from national and international security to human rights and civil liberties, technological and industrial innovation, and socio-economic development. On this basis, if capacity building in cybersecurity ever was a distinct and autonomous activity, then its chances of remaining so are slim as it becomes part and parcel of the general political discourse. As awareness of cybersecurity sharpens, and as economic and social dependency on the Internet becomes ever more pronounced, so the security and prosperity of cyberspace will be at the heart of any evolving or new public policy debate around the world. This chapter argues that cybersecurity capacity building has become much less a specialized, niche activity and much more a norm.

Unplanned Coordination: Ensemble Improvisation as Collective Action

The characteristic features of ensemble dance improvisation (EDI) make it an interesting case for theories of intentional collective action. These features include the high degree of freedom enjoyed by each individual, and the lack of fixed hierarchical roles, rigid decision procedures, or detailed plans. We present a “reductive” approach to collective action, apply it to EDI, and show how the theory enriches our perspective on this practice. We show, with the help of our theory of collective action, that EDI (as typically practiced) constitutes a significant collective achievement, one that manifests an impressive, spontaneous, jointly cooperative and individually highly autonomous activity that meets demanding aesthetic standards. Its being good in this way is not a mere extrinsic feature of the artwork, but part of its aesthetic value. We end by discussing how this value is easily missed by classic aesthetics, but is revealed by more contemporary frameworks like social aesthetics.

CaMKII holoenzyme mechanisms that govern the LTP versus LTD decision

Higher brain functions are thought to require synaptic frequency decoding that can lead to long-term potentiation (LTP) or depression (LTD). We show that the LTP versus LTD decision is determined by complex cross-regulation of T286 and T305/306 autophosphorylation within the 12meric CaMKII holoenzyme, which enabled molecular computation of stimulus frequency, amplitude, and duration. Both LTP and LTD require T286 phosphorylation, but T305/306 phosphorylation selectively promoted LTD. In response to excitatory LTP versus LTD stimuli, the differential T305/306 phosphorylation directed CaMKII movement to either excitatory or inhibitory synapses, thereby coordinating plasticity at both synapse types. Fast T305/306 phosphorylation required prior T286 phosphorylation and then curbed CaMKII activity by two mechanisms: (i) a cis-subunit reaction reduced both Ca2+ stimulation and autonomous activity and (ii) a trans-subunit reaction enabled complete activity shutdown and feed-forward inhibition of further T286 phosphorylation. These are fundamental additions to the long-studied CaMKII regulation and function in neuronal plasticity.

An Evaluation of Symmetries in Ground Reaction Forces during Self-Paced Single- and Dual-Task Treadmill Walking in the Able-Bodied Men

Gait is a complex autonomous activity that has long been viewed as a symmetrical locomotion, even when it adapts to secondary concurrent attention-demanding tasks. This study aimed to evaluate the symmetry of the three ground reaction forces (GRFs) in able-bodied individuals during self-paced treadmill walking with and without concurrent cognitive demands. Twenty-five male participants (age: 34.00 ± 4.44 years) completed two gait assessment sessions, each of whom were familiarized with the walking trials during their first session. Both sessions involved six-minute self-paced treadmill walking under three conditions: single-task walking and walking while concurrently responding to auditory 1-back and 2-back memory tasks. The symmetry of the GRFs was estimated using a nonlinear approach. Changes in the symmetry and walking speed across conditions in both sessions were assessed using inferential statistics. Results demonstrated that the three GRFs deviated from perfect symmetry by ≥10%. Engaging working memory during walking significantly reduced the symmetry of the vertical GRF (p = 0.003), and its detrimental effects on walking speed were significantly reduced in the second session with respect to the first session (p < 0.05). The findings indicate imperfect gait symmetry in able-bodied individuals, suggesting that common perceptions of gait symmetry should be reconsidered to reflect its objective importance in clinical settings.

Homeoprotein transduction in neurodevelopment and physiopathology

Homeoproteins were originally identified for embryonic cell–autonomous transcription activity, but they also have non–cell-autonomous activity owing to transfer between cells. This Review discusses transfer mechanisms and focuses on some established functions, such as neurodevelopmental regulation of axon guidance, and postnatal critical periods of brain plasticity that affect sensory processing and cognition. Homeoproteins are present across all eukaryotes, and intercellular transfer occurs in plants and animals. Proposed functions have evolutionary relevance, such as morphogenetic activity and sexual exchange during the mating of unicellular eukaryotes, while others have physiopathological relevance, such as regulation of mood and cognition by influencing brain compartmentalization, connectivity, and plasticity. There are more than 250 known homeoproteins with conserved transfer domains, suggesting that this is a common mode of signal transduction but with many undiscovered functions.

OTX2 non-cell autonomous activity regulates inner retinal function

OTX2 is a homeoprotein transcription factor expressed in photoreceptors and bipolar cells in the retina. OTX2, like many other homeoproteins, transfers between cells and exerts non-cell autonomous effects such as promoting survival of retinal ganglion cells that do not express the protein. Here we used a genetic approach to target extracellular OTX2 in the retina by conditional expression of a secreted single chain anti-OTX2 antibody. Compared to control mice, the expression of this antibody by Parvalbumin-expressing neurons in the retina is followed by a reduction in visual acuity in one-month-old mice with no alteration of the retinal structure or cell type number or aspect. A- and b-waves measured by electroretinogram were also indistinguishable from control mice, suggesting no functional deficit of photoreceptors and bipolar cells. Mice expressing the OTX2-neutralizing antibody did show a significant doubling in the flicker amplitude, consistent with a change in inner retinal function. Our results show that interfering in vivo with OTX2 non-cell autonomous activity in the postnatal retina leads to an alteration in inner retinal cell functions and causes a deficit in visual acuity.Significance statementOTX2 is a homeoprotein transcription factor expressed in retinal photoreceptors and bipolar cells. Although the Otx2 locus is silent in the inner retina, the protein is detected in cells of the ganglion cell layer consistent with the ability of this class of proteins to transfer between cells. We expressed a secreted single chain antibody (scFv) against OTX2 in the retina to neutralize extracellular OTX2. Antibody expression leads to reduced visual acuity with no change in retinal structure, or photoreceptor or bipolar physiology; however, activity in the inner retina was altered. Thus, interfering with OTX2 non-cell autonomous activity in postnatal retina alters inner retinal function and causes vision loss, highlighting the physiological value of homeoprotein direct non-cell autonomous signaling.