b.Organ transplant patients have poor immune responses to COVID-19 vaccines; thus designing vaccine strategies to protect this vulnerable population from SARS-CoV-2 infection is crucial.A central feature of the SARS-CoV-2 pandemic is that some individuals become severely ill or die, whereas others have only a mild disease course or are asymptomatic. Here we report development of an improved multimeric αβ T cell staining reagent platform, with each maxi-ferritin "spheromer" displaying 12 peptide-MHC complexes. Spheromers stain specific T cells more efficiently than peptide-MHC tetramers and capture a broader portion of the sequence repertoire for a given peptide-MHC. Analyzing the response in unexposed individuals, we find that T cells recognizing peptides conserved amongst coronaviruses are more abundant and tend to have a "memory" phenotype, compared to those unique to SARS-CoV-2. Significantly, CD8+ T cells with these conserved specificities are much more abundant in COVID-19 patients with mild disease versus those with a more severe illness, suggesting a protective role.Following stroke, the survival of neurons and their ability to reestablish connections is critical to functional recovery. This is strongly influenced by the balance between neuronal excitation and inhibition. In the acute phase of experimental stroke, lethal hyperexcitability can be attenuated by positive allosteric modulation of GABAA receptors (GABAARs). Conversely, in the late phase, negative allosteric modulation of GABAAR can correct the suboptimal excitability and improves both sensory and motor recovery. Here, we hypothesized that octadecaneuropeptide (ODN), an endogenous allosteric modulator of the GABAAR synthesized by astrocytes, influences the outcome of ischemic brain tissue and subsequent functional recovery. We show that ODN boosts the excitability of cortical neurons, which makes it deleterious in the acute phase of stroke. However, if delivered after day 3, ODN is safe and improves motor recovery over the following month in two different paradigms of experimental stroke in mice. Furthermore, we bring evidence that, during the subacute period after stroke, the repairing cortex can be treated with ODN by means of a single hydrogel deposit into the stroke cavity.SIGNIFICANCE STATEMENT Stroke remains a devastating clinical challenge because there is no efficient therapy to either minimize neuronal death with neuroprotective drugs or to enhance spontaneous recovery with neurorepair drugs. Around the brain damage, the peri-infarct cortex can be viewed as a reservoir of plasticity. However, the potential of wiring new circuits in these areas is restrained by a chronic excess of GABAergic inhibition. Here we show that an astrocyte-derived peptide, can be used as a delayed treatment, to safely correct cortical excitability and facilitate sensorimotor recovery after stroke.Textbook descriptions of primary sensory cortex (PSC) revolve around single neurons' representation of low-dimensional sensory features, such as visual object orientation in V1, location of somatic touch in S1, and sound frequency in A1.  https://www.selleckchem.com/products/reparixin-repertaxin.html  Typically, studies of PSC measure neurons' responses along few (1 or 2) stimulus and/or behavioral dimensions. However, real-world stimuli usually vary along many feature dimensions and behavioral demands change constantly. In order to illuminate how A1 supports flexible perception in rich acoustic environments, we recorded from A1 neurons while rhesus macaques (one male, one female) performed a feature-selective attention task. We presented sounds that varied along spectral and temporal feature dimensions (carrier bandwidth and temporal envelope, respectively). Within a block, subjects attended to one feature of the sound in a selective change detection task. We found that single neurons tend to be high-dimensional, in that they exhibit substantial mixed selectivity for bothund no average increase in responsiveness to, or encoding of, the attended feature across single neurons. However, when we pooled the activity of the sampled neurons via targeted dimensionality reduction, we found enhanced population-level representation of the attended feature and suppression of the distractor feature. This dissociation of the effects of attention at the level of single neurons vs. the population highlights the synergistic nature of cortical sound encoding and enriches our understanding of sensory cortical function.Our current understanding of synergistic muscle control is based on the analysis of muscle activities. Modules (synergies) in muscle coordination are extracted from electromyographic (EMG) signal envelopes. Each envelope indirectly reflects the neural drive received by a muscle; therefore, it carries information on the overall activity of the innervating motor neurons. However, it is not known whether the output of spinal motor neurons, whose number is orders of magnitude greater than the muscles they innervate, is organized in a low-dimensional fashion when performing complex tasks. Here, we hypothesized that motor neuron activities exhibit a synergistic organization in complex tasks and therefore that the common input to motor neurons results in a large dimensionality reduction in motor neuron outputs. To test this hypothesis, we factorized the output spike trains of motor neurons innervating 14 intrinsic and extrinsic hand muscles and analyzed the dimensionality of control when healthy individuals exerted ionality (implying a >10-fold reduction in dimensionality) and structure as muscle synergies. Nonetheless, the synergistic behavior of subsets of motor neurons within a muscle was also observed. These results advance our understanding of how neuromuscular control arises from mapping descending inputs to muscle activation signals. We provide, for the first time, insights into the organization of neural inputs to spinal motor neurons which, to date, has been inferred through analysis of muscle synergies.The adaptable transcriptional response to changes in food availability not only ensures animal survival but also lets embryonic development progress. Interestingly, the CNS is preferentially protected from periods of malnutrition, a phenomenon known as "brain sparing." However, the mechanisms that mediate this response remain poorly understood. To get a better understanding of this, we used Drosophila melanogaster as a model, analyzing the transcriptional response of neural stem cells (neuroblasts) and glia of the blood-brain barrier (BBB) from larvae of both sexes during nutrient restriction using targeted DamID. We found differentially expressed genes in both neuroblasts and glia of the BBB, although the effect of nutrient deficiency was primarily observed in the BBB. We characterized the function of a nutritional sensitive gene expressed in the BBB, the serine protease homolog, scarface (scaf). Scaf is expressed in subperineurial glia in the BBB in response to nutrition. Tissue-specific knockdown of scaf increases subperineurial glia endoreplication and proliferation of perineurial glia in the blood-brain barrier.