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Human NK cells are comprised of phenotypic subsets, whose potentially unique functions remain largely unexplored. C-X-C-motif-chemokine-receptor-6 (CXCR6) + NK cells have been identified as phenotypically immature tissue-resident NK cells in mice and humans. A small fraction of peripheral blood (PB)-NK cells also expresses CXCR6. However, prior reports about their phenotypic and functional plasticity are conflicting. In this study, we isolated, expanded, and phenotypically and functionally evaluated CXCR6 + and CXCR6 – PB-NK cells, and contrasted results to bulk liver and spleen NK cells. We found that CXCR6 + and CXCR6 – PB-NK cells preserved their distinct phenotypic profiles throughout 14 days of in vitro expansion (“day 14”), after which phenotypically immature CXCR6 + PB-NK cells became functionally equivalent to CXCR6 – PB-NK cells. Despite a consistent reduction in CD16 expression and enhanced expression of the transcription factor Eomesodermin (Eomes), day 14 CXCR6 + PB-NK cells had superior antibody-dependent cellular cytotoxicity (ADCC) compared to CXCR6 – PB-NK cells. Further, bulk liver NK cells responded to IL-15, but not IL-2 stimulation, with STAT-5 phosphorylation. In contrast, bulk splenic and PB-NK cells robustly responded to both cytokines. Our findings may allow for the selection of superior NK cell subsets for infusion products increasingly used to treat human diseases.

Recent work has shown that dispersal has an important role in shaping microbial communities. However, little is known about how dispersed bacteria cope with new environmental conditions and how they compete with local resident communities. To test this, we implemented two full-factorial transplant experiments with bacterial communities originating from two sources (freshwater or saline water), which were incubated, separately or in mixes, under both environmental conditions. Thus, we were able to separately test for the effects of the new environment with and without interactions with local communities. We determined community composition using 454-pyrosequencing of bacterial 16S rRNA to specifically target the active fraction of the communities, and measured several functional parameters. In absence of a local resident community, the net functional response was mainly affected by the environmental conditions, suggesting successful functional adaptation to the new environmental conditions. Community composition was influenced both by the source and the incubation environment, suggesting simultaneous effects of species sorting and functional plasticity. In presence of a local resident community, functional parameters were higher compared with those expected from proportional mixes of the unmixed communities in three out of four cases. This was accompanied by an increase in the relative abundance of generalists, suggesting that competitive interactions among local and immigrant taxa could explain the observed ‘functional overachievement’. In summary, our results suggest that environmental filtering, functional plasticity and competition are all important mechanisms influencing the fate of dispersed communities.

Traumatic brain injury (TBI) is a major cause of death and long-term disability worldwide. To date, there are no effective pharmacological treatments for TBI. Recombinant human tissue plasminogen activator (tPA) is the effective drug for the treatment of acute ischemic stroke. In addition to its thrombolytic effect, tPA is also involved in neuroplasticity in the central nervous system. However, tPA has potential adverse side effects when administered intravenously including brain edema and hemorrhage. Here we report that tPA, administered by intranasal delivery during the subacute phase after TBI, provides therapeutic benefit. Animals with TBI were treated intranasally with saline or tPA initiated 7 days after TBI. Compared with saline treatment, subacute intranasal tPA treatment significantly 1) improved cognitive (Morris water maze test) and sensorimotor (footfault and modified neurological severity score) functional recovery in rats after TBI, 2) reduced the cortical stimulation threshold evoking ipsilateral forelimb movement, 3) enhanced neurogenesis in the dentate gyrus and axonal sprouting of the corticospinal tract originating from the contralesional cortex into the denervated side of the cervical gray matter, and 4) increased the level of mature brain-derived neurotrophic factor. Our data suggest that subacute intranasal tPA treatment improves functional recovery and promotes brain neurogenesis and spinal cord axonal sprouting after TBI, which may be mediated, at least in part, by tPA/plasmin-dependent maturation of brain-derived neurotrophic factor.

Aquaporins in rice (Oryza sativa L.) represent a pivotal class of transmembrane channel proteins that mediate the bidirectional transport of water and small solutes, which have critical functions in cellular osmoregulation and ion homeostasis maintenance. Their evolutionary diversity and functional plasticity constitute fundamental mechanisms underlying the adaptive responses to diversified environmental challenges. This review systematically summarizes rice AQPs’ evolutionary origins, structural characteristics, and spatiotemporal expression patterns under both physiological and stress conditions, highlighting the high conservation of their key functional domains across evolution and their environment-driven functional diversification. The molecular mechanisms governing AQPs in water utilization, nutrient uptake, and stress responses are unraveled. Furthermore, the potential of precision gene editing and multi-omics integration is discussed to decipher the intricate relationships between AQP evolutionary history, environmental adaptability, and functional specialization, thereby providing a theoretical basis for advancing crop stress resistance and high-quality breeding.

The auditory system of adult listeners has been shown to accommodate to altered spectral cues to sound location which presumably provides the basis for recalibration to changes in the shape of the ear over a life time. Here we review the role of auditory and non-auditory inputs to the perception of sound location and consider a range of recent experiments looking at the role of non-auditory inputs in the process of accommodation to these altered spectral cues. A number of studies have used small ear molds to modify the spectral cues that result in significant degradation in localization performance. Following chronic exposure (10-60 days) performance recovers to some extent and recent work has demonstrated that this occurs for both audio-visual and audio-only regions of space. This begs the questions as to the teacher signal for this remarkable functional plasticity in the adult nervous system. Following a brief review of influence of the motor state in auditory localization, we consider the potential role of auditory-motor learning in the perceptual recalibration of the spectral cues. Several recent studies have considered how multi-modal and sensory-motor feedback might influence accommodation to altered spectral cues produced by ear molds or through virtual auditory space stimulation using non-individualized spectral cues. The work with ear molds demonstrates that a relatively short period of training involving audio-motor feedback (5-10 days) significantly improved both the rate and extent of accommodation to altered spectral cues. This has significant implications not only for the mechanisms by which this complex sensory information is encoded to provide spatial cues but also for adaptive training to altered auditory inputs. The review concludes by considering the implications for rehabilitative training with hearing aids and cochlear prosthesis.

Abiotic and biotic factors have considerable impact on the plasticity of plant functional traits, which influences forest structure and productivity; however, their inter-relationships have not been quantified for fragmented tropical dry forest (TDF) ecosystems. We asked the following questions: (1) what are the variations in the plasticity of functional traits due to soil moisture availability in TDF fragments? (2) what are the roles of soil nutrients and forest disturbances in influencing variations in the plasticity of functional traits in the TDF fragments? and (3) how do the variations in the plasticity of functional traits influence the structure and productivity of TDF fragments? Based on linear mixed-effects results, we observed significant variations among tree species for soil moisture content (SMC) under the canopy and selected functional traits across forest fragments. We categorized tree species across fragments by principal component analysis (PCA) and hierarchical clustering on principal components (HCPC) analyses into three functional types, viz ., low wood density high deciduous (LWHD), high wood density medium deciduous (HWMD), and high wood density low deciduous (HWLD). Assemblage of functional traits suggested that the LWHD functional type exhibits a drought-avoiding strategy, whereas HWMD and HWLD adopt a drought-tolerant strategy. Our study showed that the variations in functional trait plasticity and the structural attributes of trees in the three functional types exhibit contrasting affinity with SMC, soil nutrients, and disturbances, although the LWHD functional type was comparatively more influenced by soil resources and disturbances compared to HWMD and HWLD along the declining SMC and edge distance gradients. Plasticity in functional traits for the LWHD functional type exhibited greater variations in traits associated with the conservation of water and resources, whereas for HWMD and HWLD, the traits exhibiting greater plasticity were linked with higher productivity and water transport. The cumulative influence of SMC, disturbances, and functional trait variations was also visible in the relative abundance of functional types in large and small sized fragments. Our analysis further revealed the critical differences in the responses of functional trait plasticity of the coexisting tree species in TDF, which suggests that important deciduous endemic species with drought-avoiding strategies might be prone to strategic exclusion under expected rises in anthropogenic disturbances, habitat fragmentation, and resource limitations.

While gamma delta T cell (γδTc) anticancer immunotherapies are being developed, recent reports suggest a regulatory role for γδTc tumor-infiltrating lymphocytes. This mini-review surveys available evidence, determines strengths and weaknesses thereof and suggest directions for further exploration. We focus on human γδTc, as mouse and human γδTc repertoires differ. Regulatory γδTc are defined and compared to conventional Tregs and their roles in health and disease (focusing in on cancer) are discussed. We contrast the suggested regulatory roles for γδTc in breast and colorectal cancer with their cytotoxic capabilities in other malignancies, emphasizing the context dependence of γδTc functional plasticity. Since γδTc can be induced to exhibit regulatory properties (in some cases reversible), we carefully scrutinize experimental procedures in published reports. As γδTc garner increasing interest for their therapeutic potential, it is critical that we appreciate the full extent of their role(s) and interactions with other cell types in both the circulation and the tumor microenvironment. A comprehensive understanding will enable manipulation of γδTc to improve anti-tumor efficacy and patient outcomes.

Synaptic plasticity, the putative basis of learning and memory formation, manifests in various forms and across different timescales. Here we show that the interaction of Hebbian homosynaptic plasticity with rapid non-Hebbian heterosynaptic plasticity is, when complemented with slower homeostatic changes and consolidation, sufficient for assembly formation and memory recall in a spiking recurrent network model of excitatory and inhibitory neurons. In the model, assemblies were formed during repeated sensory stimulation and characterized by strong recurrent excitatory connections. Even days after formation, and despite ongoing network activity and synaptic plasticity, memories could be recalled through selective delay activity following the brief stimulation of a subset of assembly neurons. Blocking any component of plasticity prevented stable functioning as a memory network. Our modelling results suggest that the diversity of plasticity phenomena in the brain is orchestrated towards achieving common functional goals. The brain exhibits a diversity of plasticity mechanisms across different timecales that constitute the putative basis for learning and memory. Here, the authors demonstrate how these different plasticity mechanisms are orchestrated to support the formation of robust and stable neural cell assemblies.

We summarize here the results presented and subsequent discussion from the meeting on Integrating Hebbian and Homeostatic Plasticity at the Royal Society in April 2016. We first outline the major themes and results presented at the meeting. We next provide a synopsis of the outstanding questions that emerged from the discussion at the end of the meeting and finally suggest potential directions of research that we believe are most promising to develop an understanding of how these two forms of plasticity interact to facilitate functional changes in the brain. This article is part of the themed issue ‘Integrating Hebbian and homeostatic plasticity’.

•A network analysis combined fMRI and immunohistochemistry was performed on operant learning.•Functional connectivity in limbic areas increased at early stage of training.•Functional connectivity in sensorimotor cortex increased at late stage of training.•These connectivity changes in fMRI were validated using EGR1 immunohistochemistry. Previous studies of operant learning have addressed neuronal activities and network changes in specific brain areas, such as the striatum, sensorimotor cortex, prefrontal/orbitofrontal cortices, and hippocampus. However, how changes in the whole-brain network are caused by cellular-level changes remains unclear. We, therefore, combined resting-state functional magnetic resonance imaging (rsfMRI) and whole-brain immunohistochemical analysis of early growth response 1 (EGR1), a marker of neural plasticity, to elucidate the temporal and spatial changes in functional networks and underlying cellular processes during operant learning. We used an 11.7-Tesla MRI scanner and whole-brain immunohistochemical analysis of EGR1 in mice during the early and late stages of operant learning. In the operant training, mice received a reward when they pressed left and right buttons alternately, and were punished with a bright light when they made a mistake. A group of mice (n = 22) underwent the first rsfMRI acquisition before behavioral sessions, the second acquisition after 3 training-session-days (early stage), and the third after 21 training-session-days (late stage). Another group of mice (n = 40) was subjected to histological analysis 15 min after the early or late stages of behavioral sessions. Functional connectivity increased between the limbic areas and thalamus or auditory cortex after the early stage of training, and between the motor cortex, sensory cortex, and striatum after the late stage of training. The density of EGR1-immunopositive cells in the motor and sensory cortices increased in both the early and late stages of training, whereas the density in the amygdala increased only in the early stage of training. The subcortical networks centered around the limbic areas that emerged in the early stage have been implicated in rewards, pleasures, and fears. The connectivities between the motor cortex, somatosensory cortex, and striatum that consolidated in the late stage have been implicated in motor learning. Our multimodal longitudinal study successfully revealed temporal shifts in brain regions involved in behavioral learning together with the underlying cellular-level plasticity between these regions. Our study represents a first step towards establishing a new experimental paradigm that combines rsfMRI and immunohistochemistry to link macroscopic and microscopic mechanisms involved in learning.