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1.
Behav Sci (Basel) ; 14(6)2024 May 31.
Article in English | MEDLINE | ID: mdl-38920802

ABSTRACT

The aim of this study was to investigate the impact of extended bridge expertise on rapid perceptual processing and brain functional plasticity in early adulthood, utilizing functional magnetic resonance imaging (fMRI). In this investigation, we compared 6 high-level college bridge players with 25 college students lacking bridge experience, assessing their intelligence and working memory. Additionally, we scrutinized behavioral performance and whole-brain activation patterns during an image perceptual judgment task. Findings indicated significant group and interaction effects at the behavioral level. Bridge players exhibited prolonged reaction times and enhanced accuracy on card tasks. At the neural level, the activation level of bridge players in the occipital lobe exceeded that of ordinary college students, with more pronounced group effects in the motor area and inferior parietal lobule during card tasks. This implies that bridge expertise in early adulthood induces functional plasticity changes in regions associated with visual processing and automated mathematical computation.

2.
Front Aging Neurosci ; 16: 1401991, 2024.
Article in English | MEDLINE | ID: mdl-38872625

ABSTRACT

Objective: Levodopa (L-dopa) therapy is the principal pharmacological treatment for Parkinson's disease (PD). Nevertheless, prolonged use of this drug may result in different involuntary movement symptoms caused by the medication, referred to as levodopa-induced dyskinesia (LID). LID is associated with changes in synaptic plasticity of the D1 medium spiny neurons (MSNs) located in the dorsal striatum (dStr). Within the striatum, the amount of Dopamine D3 receptor (D3R) is notably increased in LID, demonstrating colocalization with D1R expression in neurons, and the level of D3R expression is directly related to the intensity of LID. IRL 790, as a D3R antagonist, can ameliorate LID. This study aims to explore if IRL 790 improves LID by regulating the synaptic plasticity of D1+ MSNs in dStr. Methods: The electrophysiology and synaptic spine density of D1+ MSNs in dStr were recorded for sham mice, LID mice, and LID mice treated with IRL 790. The regulation of synaptic plasticity in LID D1+ MSNs by IRL 790 was analyzed. Behavioral tests were conducted to confirm the treatment effect of IRL 790 on LID. Results: In LID D1+ MSNs, there was persistent abnormal LTP, absence of LTD, and an increase in spontaneous excitatory postsynaptic currents (sEPSCs). IRL 790 treatment restored normal LTP, LTD, and sEPSCs. Treatment with IRL 790 also restored the reduced dendritic spine density in D1+ MSNs of LID mice. IRL790 improved dyskinetic manifestations in LID mice. Conclusion: IRL790 ameliorates LID by regulating the synaptic structure and functional plasticity of striatal D1+ MSNs.

3.
Protein Sci ; 33(5): e4989, 2024 May.
Article in English | MEDLINE | ID: mdl-38659213

ABSTRACT

Intrinsically disordered late embryogenesis abundant (LEA) proteins play a central role in the tolerance of plants and other organisms to dehydration brought upon, for example, by freezing temperatures, high salt concentration, drought or desiccation, and many LEA proteins have been found to stabilize dehydration-sensitive cellular structures. Their conformational ensembles are highly sensitive to the environment, allowing them to undergo conformational changes and adopt ordered secondary and quaternary structures and to participate in formation of membraneless organelles. In an interdisciplinary approach, we discovered how the functional diversity of the Arabidopsis thaliana LEA protein COR15A found in vitro is encoded in its structural repertoire, with the stabilization of membranes being achieved at the level of secondary structure and the stabilization of enzymes accomplished by the formation of oligomeric complexes. We provide molecular details on intra- and inter-monomeric helix-helix interactions, demonstrate how oligomerization is driven by an α-helical molecular recognition feature (α-MoRF) and provide a rationale that the formation of noncanonical, loosely packed, right-handed coiled-coils might be a recurring theme for homo- and hetero-oligomerization of LEA proteins.


Subject(s)
Arabidopsis Proteins , Arabidopsis , Intrinsically Disordered Proteins , Arabidopsis Proteins/chemistry , Arabidopsis Proteins/metabolism , Arabidopsis Proteins/genetics , Arabidopsis/chemistry , Arabidopsis/metabolism , Intrinsically Disordered Proteins/chemistry , Intrinsically Disordered Proteins/metabolism , Intrinsically Disordered Proteins/genetics , Freezing , Models, Molecular , Protein Multimerization , Protein Structure, Secondary
4.
Cell Host Microbe ; 32(3): 322-334.e9, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38423015

ABSTRACT

Reversible genomic DNA inversions control the expression of numerous gut bacterial molecules, but how this impacts disease remains uncertain. By analyzing metagenomic samples from inflammatory bowel disease (IBD) cohorts, we identified multiple invertible regions where a particular orientation correlated with disease. These include the promoter of polysaccharide A (PSA) of Bacteroides fragilis, which induces regulatory T cells (Tregs) and ameliorates experimental colitis. The PSA promoter was mostly oriented "OFF" in IBD patients, which correlated with increased B. fragilis-associated bacteriophages. Similarly, in mice colonized with a healthy human microbiota and B. fragilis, induction of colitis caused a decline of PSA in the "ON" orientation that reversed as inflammation resolved. Monocolonization of mice with B. fragilis revealed that bacteriophage infection increased the frequency of PSA in the "OFF" orientation, causing reduced PSA expression and decreased Treg cells. Altogether, we reveal dynamic bacterial phase variations driven by bacteriophages and host inflammation, signifying bacterial functional plasticity during disease.


Subject(s)
Colitis , Gastrointestinal Microbiome , Inflammatory Bowel Diseases , Humans , Animals , Mice , Inflammatory Bowel Diseases/microbiology , Inflammation , DNA
5.
Cell Rep ; 42(12): 113475, 2023 12 26.
Article in English | MEDLINE | ID: mdl-37979173

ABSTRACT

Evoked brain oscillations in the gamma range have been shown to assist in stroke recovery. However, the causal relationship between evoked oscillations and neuroprotection is not well understood. We have used optogenetic stimulation to investigate how evoked gamma oscillations modulate cortical dynamics in the acute phase after stroke. Our results reveal that stimulation at 40 Hz drives activity in interneurons at the stimulation frequency and phase-locked activity in principal neurons at a lower frequency, leading to increased cross-frequency coupling. In addition, 40-Hz stimulation after stroke enhances interregional communication. These effects are observed up to 24 h after stimulation. Our stimulation protocol also rescues functional synaptic plasticity 24 h after stroke and leads to an upregulation of plasticity genes and a downregulation of cell death genes. Together these results suggest that restoration of cortical dynamics may confer neuroprotection after stroke.


Subject(s)
Optogenetics , Stroke , Humans , Neurons/physiology , Interneurons/physiology , Stroke/therapy , Neuronal Plasticity/physiology
6.
Cereb Cortex ; 33(13): 8633-8644, 2023 06 20.
Article in English | MEDLINE | ID: mdl-37170657

ABSTRACT

The individual difference of intrinsic functional connectivity is increasingly acknowledged to be biologically informative and behaviorally relevant. However, such valuable information is still discounted as a stochastic variation in previous studies of cognitive training. Here, we explored the plasticity of intersubject similarity in functional connectivity (ISFC), induced by long-term abacus-based mental calculation (AMC) training. Using a longitudinal dataset (AMC: n = 40, 5-year training; Control: n = 43), we found robust training effect of enhanced ISFC, after accounting for the factor of development. Notably, the enhancement focused on selective subsets of FCs, or the "critical FCs," which predominantly impacted the default-mode and visual networks. Using a cross-sectional dataset with a larger sample (AMC: n = 93, 1/3/5-year training; Control: n = 110), we observed that the "critical FCs" and its intersubject similarity could predict mental calculation ability and its intersubject similarity, respectively, in the AMC group. However, such predictions cannot be generalized to the control group, suggesting that long-term training may be a prerequisite for establishing such brain-behavior relationships. Jointly, our findings implicated that the enhanced ISFC with profound impact on the default-mode network could be a plastic change that is associated with behavioral gains of training.


Subject(s)
Brain , Magnetic Resonance Imaging , Cross-Sectional Studies , Brain Mapping , Mathematics
7.
Tree Physiol ; 43(6): 909-924, 2023 06 07.
Article in English | MEDLINE | ID: mdl-36809504

ABSTRACT

Forests are threatened globally by increased recurrence and intensity of hot droughts. Functionally close coexisting species may exhibit differences in drought vulnerability large enough to cause niche differentiation and affect forest dynamics. The effect of rising atmospheric [CO2], which could partly alleviate the negative effects of drought, may also differ between species. We analysed functional plasticity in seedlings of two taxonomically close pine species (Pinus pinaster Ait., Pinus pinea L.) under different [CO2] and water stress levels. The multidimensional functional trait variability was more influenced by water stress (preferentially xylem traits) and [CO2] (mostly leaf traits) than by differences between species. However, we observed differences between species in the strategies followed to coordinate their hydraulic and structural traits under stress. Leaf 13C discrimination decreased with water stress and increased under elevated [CO2]. Under water stress both species increased their sapwood area to leaf area ratios, tracheid density and xylem cavitation, whereas they reduced tracheid lumen area and xylem conductivity. Pinus pinea was more anisohydric than P. pinaster. Pinus pinaster produced larger conduits under well-watered conditions than P. pinea. Pinus pinea was more tolerant to water stress and more resistant to xylem cavitation under low water potentials. The higher xylem plasticity in P. pinea, particularly in tracheid lumen area, expressed a higher capacity of acclimation to water stress than P. pinaster. In contrast, P. pinaster coped with water stress comparatively more by increasing plasticity of leaf hydraulic traits. Despite the small differences observed in the functional response to water stress and drought tolerance between species, these interspecific differences agreed with ongoing substitution of P. pinaster by P. pinea in forests where both species co-occur. Increased [CO2] had little effect on the species-specific relative performance. Thus, a competitive advantage under moderate water stress of P. pinea compared with P. pinaster is expected to continue in the future.


Subject(s)
Drought Resistance , Pinus , Carbon Dioxide , Dehydration , Plant Leaves/physiology , Acclimatization , Xylem/physiology , Droughts , Pinus/physiology
8.
Immunol Cell Biol ; 101(2): 112-129, 2023 02.
Article in English | MEDLINE | ID: mdl-36479949

ABSTRACT

FOXP3-expressing regulatory T cells (Treg ) are indispensable for immune homeostasis and tolerance, and in addition tissue-resident Treg have been found to perform noncanonical, tissue-specific functions. For optimal tolerogenic function during inflammatory disease, Treg are equipped with mechanisms that assure lineage stability. Treg lineage stability is closely linked to the installation and maintenance of a lineage-specific epigenetic landscape, specifically a Treg -specific DNA demethylation pattern. At the same time, for local and directed immune regulation Treg must possess a level of functional plasticity that requires them to partially acquire T helper cell (TH ) transcriptional programs-then referred to as TH -like Treg . Unleashing TH programs in Treg , however, is not without risk and may threaten the epigenetic stability of Treg with consequently pathogenic ex-Treg contributing to (auto-) inflammatory conditions. Here, we review how the Treg -stabilizing epigenetic landscape is installed and maintained, and further discuss the development, necessity and lineage instability risks of TH 1-, TH 2-, TH 17-like Treg and follicular Treg .


Subject(s)
Immune Tolerance , T-Lymphocytes, Regulatory , Forkhead Transcription Factors
9.
Cells ; 11(17)2022 08 28.
Article in English | MEDLINE | ID: mdl-36078087

ABSTRACT

It is well established that plant thylakoid membranes (TMs), in addition to a bilayer, contain two isotropic lipid phases and an inverted hexagonal (HII) phase. To elucidate the origin of non-bilayer lipid phases, we recorded the 31P-NMR spectra of isolated spinach plastoglobuli and TMs and tested their susceptibilities to lipases and proteases; the structural and functional characteristics of TMs were monitored using biophysical techniques and CN-PAGE. Phospholipase-A1 gradually destroyed all 31P-NMR-detectable lipid phases of isolated TMs, but the weak signal of isolated plastoglobuli was not affected. Parallel with the destabilization of their lamellar phase, TMs lost their impermeability; other effects, mainly on Photosystem-II, lagged behind the destruction of the original phases. Wheat-germ lipase selectively eliminated the isotropic phases but exerted little or no effect on the structural and functional parameters of TMs-indicating that the isotropic phases are located outside the protein-rich regions and might be involved in membrane fusion. Trypsin and Proteinase K selectively suppressed the HII phase-suggesting that a large fraction of TM lipids encapsulate stroma-side proteins or polypeptides. We conclude that-in line with the Dynamic Exchange Model-the non-bilayer lipid phases of TMs are found in subdomains separated from but interconnected with the bilayer accommodating the main components of the photosynthetic machinery.


Subject(s)
Lipid Bilayers , Thylakoids , Lipase/metabolism , Lipid Bilayers/metabolism , Magnetic Resonance Spectroscopy , Peptide Hydrolases/metabolism , Thylakoids/metabolism
10.
Gen Comp Endocrinol ; 326: 114071, 2022 09 15.
Article in English | MEDLINE | ID: mdl-35697315

ABSTRACT

Salinity is one of the main physical properties that govern the distribution of fishes across aquatic habitats. In order to maintain their body fluids near osmotic set points in the face of salinity changes, euryhaline fishes rely upon tissue-level osmotically-induced responses and systemic endocrine signaling to direct adaptive ion-transport processes in the gill and other critical osmoregulatory organs. Some euryhaline teleosts inhabit tidally influenced waters such as estuaries where salinity can vary between fresh water (FW) and seawater (SW). The physiological adaptations that underlie euryhalinity in teleosts have been traditionally identified in fish held under steady-state conditions or following unidirectional transfers between FW and SW. Far fewer studies have employed salinity regimes that simulate the tidal cycles that some euryhaline fishes may experience in their native habitats. With an emphasis on prolactin (Prl) signaling and branchial ionocytes, this mini-review contrasts the physiological responses between euryhaline fish responding to tidal versus unidirectional changes in salinity. Three patterns that emerged from studying Mozambique tilapia (Oreochromis mossambicus) subjected to tidally-changing salinities include, 1) fish can compensate for continuous and marked changes in external salinity to maintain osmoregulatory parameters within narrow ranges, 2) tilapia maintain branchial ionocyte populations in a fashion similar to SW-acclimated fish, and 3) there is a shift from systemic to local modulation of Prl signaling.


Subject(s)
Salinity , Tilapia , Acclimatization/physiology , Animals , Gills/metabolism , Osmoregulation , Prolactin/metabolism , Seawater , Tilapia/metabolism , Water-Electrolyte Balance/physiology
11.
Int J Mol Sci ; 23(9)2022 Apr 20.
Article in English | MEDLINE | ID: mdl-35562946

ABSTRACT

Depression is a psychiatric disorder that presents with a persistent depressed mood as the main clinical feature and is accompanied by cognitive impairment. Changes in neuroplasticity and neurogenesis greatly affect depression. Without genetic changes, epigenetic mechanisms have been shown to function by regulating gene expression during the body's adaptation to stress. Studies in recent years have shown that as important regulatory factors in epigenetic mechanisms, microRNAs (miRNAs) play important roles in the development and progression of depression through the regulation of protein expression. Herein, we review the mechanisms of miRNA-mediated neuroplasticity in depression and discus synaptic structural plasticity, synaptic functional plasticity, and neurogenesis. Furthermore, we found that miRNAs regulate neuroplasticity through several signalling pathways to affect cognitive functions. However, these pathways do not work independently. Therefore, we try to identify synergistic correlations between miRNAs and multiple signalling pathways to broaden the potential pathogenesis of depression. In addition, in the future, dual-function miRNAs (protection/injury) are promising candidate biomarkers for the diagnosis of depression, and their regulated genes can potentially be used as target genes for the treatment of depression.


Subject(s)
Cognitive Dysfunction , MicroRNAs , Depression/genetics , Humans , MicroRNAs/metabolism , Neurogenesis/genetics , Neuronal Plasticity/genetics
12.
Cereb Cortex ; 32(20): 4422-4435, 2022 10 08.
Article in English | MEDLINE | ID: mdl-35106532

ABSTRACT

Vision is a key source of information input for humans, which involves various cognitive functions and a great range of neural networks inside and beyond the visual cortex. There has been increasing observation that the cognitive outcomes after a brain lesion cannot be well predicted by the attributes of the lesion itself but are influenced by the functional network plasticity. However, the mechanisms of impaired or preserved visual cognition have not been probed from direct function-execution conditions and few works have observed it on whole-brain dynamic networks. We used high-resolution electroencephalogram recordings from 25 patients with brain tumors to track the dynamical patterns of functional reorganization in visual processing tasks with multilevel complexity. By comparing with 24 healthy controls, increased cortical responsiveness as functional compensation was identified in the early phase of processing, which was highly localized to the visual cortex and functional networks and less relevant to the tumor position. Besides, a spreading wide enhancement in whole-brain functional connectivity was elicited by the visual word-recognition task. Enhanced early rapid-onset cortical compensation in the local functional networks may contribute to largely preserved basic vision functions, and higher-cognitive tasks are vulnerable to impairment but with high sensitivity of functional plasticity being elicited.


Subject(s)
Brain Neoplasms , Visual Cortex , Brain , Brain Mapping , Brain Neoplasms/diagnostic imaging , Cognition , Humans , Magnetic Resonance Imaging , Neural Networks, Computer , Neural Pathways , Visual Perception
13.
Chembiochem ; 23(5): e202100484, 2022 03 04.
Article in English | MEDLINE | ID: mdl-34669250

ABSTRACT

Terpenoids are a highly diverse group of natural products with considerable industrial interest. Increasingly, engineered microbes are used for the production of terpenoids to replace natural extracts and chemical synthesis. Terpene synthases (TSs) show a high level of functional plasticity and are responsible for the vast structural diversity observed in natural terpenoids. Their relatively inert active sites guide intrinsically reactive linear carbocation intermediates along one of many cyclisation paths via exertion of subtle steric and electrostatic control. Due to the absence of a strong protein interaction with these intermediates, there is a remarkable lack of sequence-function relationship within the TS family, making product-outcome predictions from sequences alone challenging. This, in combination with the fact that many TSs produce multiple products from a single substrate hampers the design and use of TSs in the biomanufacturing of terpenoids. This review highlights recent advances in genome mining, computational modelling, high-throughput screening, and machine-learning that will allow more predictive engineering of these fascinating enzymes in the near future.


Subject(s)
Alkyl and Aryl Transferases , Alkyl and Aryl Transferases/genetics , Alkyl and Aryl Transferases/metabolism , Catalytic Domain , Cyclization , Terpenes/metabolism
14.
Front Immunol ; 12: 748423, 2021.
Article in English | MEDLINE | ID: mdl-34691060

ABSTRACT

The Type I Interferon family of cytokines all act through the same cell surface receptor and induce phosphorylation of the same subset of response regulators of the STAT family. Despite their shared receptor, different Type I Interferons have different functions during immune response to infection. In particular, they differ in the potency of their induced anti-viral and anti-proliferative responses in target cells. It remains not fully understood how these functional differences can arise in a ligand-specific manner both at the level of STAT phosphorylation and the downstream function. We use a minimal computational model of Type I Interferon signaling, focusing on Interferon-α and Interferon-ß. We validate the model with quantitative experimental data to identify the key determinants of specificity and functional plasticity in Type I Interferon signaling. We investigate different mechanisms of signal discrimination, and how multiple system components such as binding affinity, receptor expression levels and their variability, receptor internalization, short-term negative feedback by SOCS1 protein, and differential receptor expression play together to ensure ligand specificity on the level of STAT phosphorylation. Based on these results, we propose phenomenological functional mappings from STAT activation to downstream anti-viral and anti-proliferative activity to investigate differential signal processing steps downstream of STAT phosphorylation. We find that the negative feedback by the protein USP18, which enhances differences in signaling between Interferons via ligand-dependent refractoriness, can give rise to functional plasticity in Interferon-α and Interferon-ß signaling, and explore other factors that control functional plasticity. Beyond Type I Interferon signaling, our results have a broad applicability to questions of signaling specificity and functional plasticity in signaling systems with multiple ligands acting through a bottleneck of a small number of shared receptors.


Subject(s)
Interferon-alpha/physiology , Interferon-beta/physiology , Models, Immunological , Receptor Cross-Talk/physiology , Receptor, Interferon alpha-beta/physiology , Signal Transduction/physiology , Animals , Computer Simulation , Dimerization , Feedback, Physiological , Female , Humans , Inhibitory Concentration 50 , Kinetics , Ligands , Mice , Mice, Inbred C57BL , Protein Binding , Protein Interaction Mapping , STAT Transcription Factors/metabolism , Spleen/cytology , Suppressor of Cytokine Signaling 1 Protein/physiology , T-Lymphocytes/immunology , Ubiquitin Thiolesterase
15.
PeerJ ; 9: e11759, 2021.
Article in English | MEDLINE | ID: mdl-34484979

ABSTRACT

BACKGROUND: Pain, a major symptom of osteonecrosis of the femoral head (ONFH), is a complex sensory and emotional experience that presents therapeutic challenges. Pain can cause neuroplastic changes at the cortical level, leading to central sensitization and difficulties with curative treatments; however, whether changes in structural and functional plasticity occur in patients with ONFH remains unclear. METHODS: A total of 23 ONFH inpatients who did not undergo surgery (14 males, nine females; aged 55.61 ± 13.79 years) and 20 controls (12 males, eight females; aged 47.25 ± 19.35 years) were enrolled. Functional indices of the amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), and a structural index of tract-based spatial statistics (TBSS) were calculated for each participant. The probability distribution of fiber direction was determined according to the ALFF results. RESULTS: ONFH patients demonstrated increased ALFF in the bilateral dorsolateral superior frontal gyrus, right medial superior frontal gyrus, right middle frontal gyrus, and right supplementary motor area. In contrast, ONFH patients showed decreased ReHo in the left superior parietal gyrus and right inferior temporal gyrus. There were no significant differences in TBSS or probabilistic tractography. CONCLUSION: These results indicate cerebral pain processing in ONFH patients. It is advantageous to use functional magnetic resonance imaging to better understand pain pathogenesis and identify new therapeutic targets in ONFH patients.

16.
Cells ; 10(7)2021 07 20.
Article in English | MEDLINE | ID: mdl-34360003

ABSTRACT

Postsynaptic structures on excitatory neurons, dendritic spines, are actin-rich. It is well known that actin-binding proteins regulate actin dynamics and by this means orchestrate structural plasticity during the development of the brain, as well as synaptic plasticity mediating learning and memory processes. The actin-binding protein cortactin is localized to pre- and postsynaptic structures and translocates in a stimulus-dependent manner between spines and the dendritic compartment, thereby indicating a crucial role for synaptic plasticity and neuronal function. While it is known that cortactin directly binds F-actin, the Arp2/3 complex important for actin nucleation and branching as well as other factors involved in synaptic plasticity processes, its precise role in modulating actin remodeling in neurons needs to be deciphered. In this study, we characterized the general neuronal function of cortactin in knockout mice. Interestingly, we found that the loss of cortactin leads to deficits in hippocampus-dependent spatial memory formation. This impairment is correlated with a prominent dysregulation of functional and structural plasticity. Additional evidence shows impaired long-term potentiation in cortactin knockout mice together with a complete absence of structural spine plasticity. These phenotypes might at least in part be explained by alterations in the activity-dependent modulation of synaptic actin in cortactin-deficient neurons.


Subject(s)
Actin Cytoskeleton/genetics , Actins/genetics , Cortactin/genetics , Hippocampus/metabolism , Spatial Memory/physiology , Spine/metabolism , Actin Cytoskeleton/metabolism , Actin-Related Protein 2-3 Complex/genetics , Actin-Related Protein 2-3 Complex/metabolism , Actins/metabolism , Animals , Cortactin/deficiency , Gene Expression Regulation , Hippocampus/physiopathology , Long-Term Potentiation/physiology , Male , Maze Learning/physiology , Mice , Mice, Inbred C57BL , Mice, Knockout , Microtomy , Neurons/metabolism , Neurons/pathology , Spine/physiopathology , Synaptic Transmission , Tissue Culture Techniques
17.
Biotechnol Biofuels ; 14(1): 147, 2021 Jun 30.
Article in English | MEDLINE | ID: mdl-34193244

ABSTRACT

Plant monoterpenoids with structural diversities have extensive applications in food, cosmetics, pharmaceuticals, and biofuels. Due to the strong dependence on the geographical locations and seasonal annual growth of plants, agricultural production for monoterpenoids is less effective. Chemical synthesis is also uneconomic because of its high cost and pollution. Recently, emerging synthetic biology enables engineered microbes to possess great potential for the production of plant monoterpenoids. Both acyclic and cyclic monoterpenoids have been synthesized from fermentative sugars through heterologously reconstructing monoterpenoid biosynthetic pathways in microbes. Acting as catalytic templates, plant monoterpene synthases (MTPSs) take elaborate control of the monoterpenoids production. Most plant MTPSs have broad substrate or product properties, and show functional plasticity. Thus, the substrate selectivity, product outcomes, or enzymatic activities can be achieved by the active site mutations and domain swapping of plant MTPSs. This makes plasticity engineering a promising way to engineer MTPSs for efficient production of natural and non-natural monoterpenoids in microbial cell factories. Here, this review summarizes the key advances in plasticity engineering of plant MTPSs, including the fundamental aspects of functional plasticity, the utilization of natural and non-natural substrates, and the outcomes from product isomers to complexity-divergent monoterpenoids. Furthermore, the applications of plasticity engineering for improving monoterpenoids production in microbes are addressed.

18.
J Neurophysiol ; 125(6): 2178-2190, 2021 06 01.
Article in English | MEDLINE | ID: mdl-33909497

ABSTRACT

The chorda tympani is a gustatory nerve that fails to regenerate if sectioned in rats 10 days of age or younger. This early denervation causes an abnormally high preference for NH4Cl in adult rats, but the impact of neonatal chorda tympani transection on the development of the gustatory hindbrain is unclear. Here, we tested the effect of neonatal chorda tympani transection (CTX) on gustatory responses in the parabrachial nucleus (PbN). We recorded in vivo extracellular spikes in single PbN units of urethane-anesthetized adult rats following CTX at P5 (chronic CTX group) or immediately prior to recording (acute CTX group). Thus, all sampled PbN neurons received indirect input from taste nerves other than the CT. Compared to acute CTX rats, chronic CTX animals had significantly higher responses to stimulation with 0.1 and 0.5 M NH4Cl, 0.1 and 0.5 M NaCl, and 0.01 M citric acid. Activity to 0.5 M sucrose and 0.01 M quinine stimulation was not significantly different between groups. Neurons from chronic CTX animals also had larger interstimulus correlations and significantly higher entropy, suggesting that neurons in this group were more likely to be activated by stimulation with multiple tastants. Although neural responses were higher in the PbN of chronic CTX rats compared to acute-sectioned controls, taste-evoked activity was much lower than observed in previous reports, suggesting permanent deficits in taste signaling. These findings demonstrate that the developing gustatory hindbrain exhibits high functional plasticity following early nerve injury.NEW & NOTEWORTHY Early and chronic loss of taste input from the chorda tympani is associated with abnormal taste behaviors. We found that compared to when the chorda tympani is sectioned acutely, chronic nerve loss leads to amplification of spared inputs in the gustatory pons, with higher response to salty and sour stimuli. Findings point to plasticity that may compensate for sensory loss, but permanent deficits in taste signaling also occur following early denervation.


Subject(s)
Chorda Tympani Nerve/injuries , Neuronal Plasticity/physiology , Parabrachial Nucleus/physiopathology , Perceptual Disorders/physiopathology , Sensory Receptor Cells/physiology , Taste Perception/physiology , Taste/physiology , Action Potentials/physiology , Animals , Animals, Newborn , Denervation , Disease Models, Animal , Female , Male , Rats , Rats, Sprague-Dawley , Signal Transduction/physiology
19.
Int J Mol Sci ; 22(5)2021 Mar 05.
Article in English | MEDLINE | ID: mdl-33807989

ABSTRACT

For a better translation from treatment designs of schizophrenia to clinical efficiency, there is a crucial need to refine preclinical animal models. In order to consider the multifactorial nature of the disorder, a new mouse model associating three factors (genetic susceptibility-partial deletion of the MAP6 gene, early-life stress-maternal separation, and pharmacological treatment-chronic Δ-9-tetrahydrocannabinol during adolescence) has recently been described. While this model depicts a schizophrenia-like phenotype, the neurobiological correlates remain unknown. Synaptic transmission and functional plasticity of the CA1 hippocampal region of male and female 3-hit mice were therefore investigated using electrophysiological recordings on the hippocampus slice. While basal excitatory transmission remained unaffected, NMDA receptor (NMDAr)-mediated long-term potentiation (LTP) triggered by theta-burst (TBS) but not by high-frequency (HFS) stimulation was impaired in 3-hit mice. Isolated NMDAr activation was not affected or even increased in female 3-hit mice, revealing a sexual dimorphism. Considering that the regulation of LTP is more prone to inhibitory tone if triggered by TBS than by HFS, the weaker potentiation in 3-hit mice suggests a deficiency of intrinsic GABA regulatory mechanisms. Indeed, NMDAr activation was increased by GABAA receptor blockade in wild-type but not in 3-hit mice. This electrophysiological study highlights dysregulations of functional properties and plasticity in hippocampal networks of 3-hit mice, one of the mechanisms suspected to contribute to the pathophysiology of schizophrenia. It also shows differences between males and females, supporting the sexual dimorphism observed in the disorder. Combined with the previously reported study, the present data reinforce the face validity of the 3-hit model that will help to consider new therapeutic strategies for psychosis.


Subject(s)
CA1 Region, Hippocampal/physiopathology , Long-Term Potentiation , Schizophrenia/physiopathology , Synaptic Transmission , Theta Rhythm , Animals , CA1 Region, Hippocampal/pathology , Disease Models, Animal , Humans , Mice , Mice, Mutant Strains , Schizophrenia/genetics , Schizophrenia/pathology
20.
Cell Rep ; 34(11): 108871, 2021 03 16.
Article in English | MEDLINE | ID: mdl-33730583

ABSTRACT

The formation and consolidation of memories are complex phenomena involving synaptic plasticity, microcircuit reorganization, and the formation of multiple representations within distinct circuits. To gain insight into the structural aspects of memory consolidation, we focus on the calyx of the Drosophila mushroom body. In this essential center, essential for olfactory learning, second- and third-order neurons connect through large synaptic microglomeruli, which we dissect at the electron microscopy level. Focusing on microglomeruli that respond to a specific odor, we reveal that appetitive long-term memory results in increased numbers of precisely those functional microglomeruli responding to the conditioned odor. Hindering memory consolidation by non-coincident presentation of odor and reward, by blocking protein synthesis, or by including memory mutants suppress these structural changes, revealing their tight correlation with the process of memory consolidation. Thus, olfactory long-term memory is associated with input-specific structural modifications in a high-order center of the fly brain.


Subject(s)
Drosophila melanogaster/physiology , Memory Consolidation/physiology , Mushroom Bodies/innervation , Nerve Net/physiology , Animals , Axons/drug effects , Axons/physiology , Drosophila melanogaster/drug effects , Drosophila melanogaster/ultrastructure , Memory Consolidation/drug effects , Memory, Long-Term/drug effects , Mushroom Bodies/drug effects , Mushroom Bodies/ultrastructure , Nerve Net/drug effects , Nerve Net/ultrastructure , Neuronal Plasticity/drug effects , Odorants , Oleic Acids/pharmacology , Pheromones/pharmacology , Synapses/drug effects , Synapses/physiology , Synapses/ultrastructure
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