SHORT-ROOT paralogs mediate feedforward regulation of D-type cyclin to promote nodule formation in soybean

Nitrogen fixation in soybean takes place in root nodules that arise from de novo cell divisions in the root cortex. Although several early nodulin genes have been identified, the mechanism behind the stimulation of cortical cell division during nodulation has not been fully resolved. Here we provide evidence that two paralogs of soybean SHORT-ROOT (GmSHR) play vital roles in soybean nodulation. Expression of GmSHR4 and GmSHR5 (GmSHR4/5) is induced in cortical cells at the beginning of nodulation, when the first cell divisions occur. The expression level of GmSHR4/5 is positively associated with cortical cell division and nodulation. Knockdown of GmSHR5 inhibits cell division in outer cortical layers during nodulation. Knockdown of both paralogs disrupts the cell division throughout the cortex, resulting in poorly organized nodule primordia with delayed vascular tissue formation. GmSHR4/5 function by enhancing cytokinin signaling and activating early nodulin genes. Interestingly, D-type cyclins act downstream of GmSHR4/5, and GmSHR4/5 form a feedforward loop regulating D-type cyclins. Overexpression of D-type cyclins in soybean roots also enhanced nodulation. Collectively, we conclude that the GmSHR4/5-mediated pathway represents a vital module that triggers cytokinin signaling and activates D-type cyclins during nodulation in soybean.

A cortical cell ensemble in the posterior parietal cortex controls past experience-dependent memory updating

When processing current sensory inputs, animals refer to related past experiences. Current information is then incorporated into the related neural network to update previously stored memories. However, the neuronal mechanism underlying the impact of memories of prior experiences on current learning is not well understood. Here, we found that a cellular ensemble in the posterior parietal cortex (PPC) that is activated during past experience mediates an interaction between past and current information to update memory through a PPC-anterior cingulate cortex circuit in mice. Moreover, optogenetic silencing of the PPC ensemble immediately after retrieval dissociated the interaction without affecting individual memories stored in the hippocampus and amygdala. Thus, a specific subpopulation of PPC cells represents past information and instructs downstream brain regions to update previous memories.

Celastrol Protects against Cerebral Ischemia/Reperfusion Injury in Mice by Inhibiting Glycolysis through Targeting HIF-1α/PDK1 Axis

Cerebral ischemia/reperfusion (I/R) injury is closely related to dysfunctional glucose metabolism. Celastrol is a bioactive compound that has been found to exhibit neuroprotective effects in cerebral ischemia, while whether it can protect against cerebral I/R injury by regulating glycolysis remains unclear. The goal of this study is to investigate the role of celastrol on cerebral I/R injury and its underlying mechanisms in transient middle cerebral artery occlusion (tMCAO) mice. Methods. To observe the protective effect of celastrol and select its optimal dosage for further study, neurological score, TTC staining, and HE staining were used to evaluate neurological function, cerebral infarct volume, and cortical cell damage, respectively. QRT-PCR and Western blot were used to detect the mRNA and protein expression of hypoxia inducible factor-1α (HIF-1α), pyruvate dehydrogenasekinase1 (PDK1), lactate dehydrogenase A (LDHA), glucose transporter1 (GLUT1), and hexokinase2 (HK2), respectively. The lactate production, ATP level, and glucose content were assessed by assay kits. Results. Our results indicated that celastrol dose-dependently improved neurological function and reduced cerebral infarct volume and cortical cell death of tMCAO mice, and its optimal dosage was 4.5 mg/kg. In addition, celastrol significantly blocked I/R-induced increase of LDHA, GLUT1, HK2, and lactate production as well as decrease of ATP level and glucose content. Moreover, celastrol inhibited the I/R-induced upregulation of HIF-1α and PDK1. Overexpression of HIF-1α by DMOG reversed the protective effect of celastrol on cerebral I/R injury and blocked celastrol-induced suppression of glycolysis. Conclusions. Taken together, these results suggested that celastrol protected against cerebral I/R injury through inhibiting glycolysis via the HIF-1α/PDK1 axis.

Cortical Neurons and Astrocytes in Intrauterine Ethanol Exposure: The Role of Exposure Time and Postnatal Timeline

Background: The state of cortical neurons and astrocytes are pointers to the health of the brain. These cells are morphologically distorted by alcohol exposure. Intrauterine alcohol exposure remains a challenge with perinatal consequences. The role of exposure time and postnatal timeline on the degree of cortical cell derangement remains a subject of controversy till date. This study therefore examines alcohol exposure and postnatal changes on brain weight, cortical neurons and astrocytes at different developmental periods. Methods: Twenty mature female Wistar rats were time-mated and grouped into 4 groups. Group 1 (control) received distilled water (2 mL/kg), Groups 2, 3 and 4 were administered 2.5 mL/kg of 20% ethanol orally on the 4th, 11th and 18th days of gestation respectively. Rats produced litters and pups' brains were harvested and processed for H&E and Golgi Cox stains at the 3rd and 6th postnatal week. Neuronal and astrocytic densities in the cerebral cortex were evaluated. Results and Conclusion: There was statistically significant increase (p<0.05) in the density of degenerating neurons at the third postnatal week and sixth postnatal weeks in the experimental groups when compared with the control. There was also statistically significant increase (p<0.05) in astrocytic density in groups 2 and 4 at the 3rd postnatal week. There was no statistically significant difference (p>0.05) in the astrocytic densities across groups at the sixth postnatal week. It was concluded that intrauterine alcohol exposure in any of the developmental periods resulted in postnatal neuronal degeneration which persisted till the 6th week. However, increased astrocytic densities is a feature of 1st and 3rd trimester alcohol exposure noted in the 3rd but absent in the 6th postnatal week.

ADAM8 Activates NLRP3 Inflammasome to Promote Cerebral Ischemia-Reperfusion Injury

Stroke is the leading cause of death and disability in humans. Strokes are classified as either ischemic or hemorrhagic. Ischemic stroke accounts for 70–80% of the cases. Inflammation is a key factor in ischemic brain injury. Studies have shown that inflammatory response induced by NLRP3 inflammasome is one of the root causes of brain damage in mice with cerebral ischemia. However, its specific mechanism in cerebral ischemia is still unclear. ADAM8 (a disintegrin and metalloproteases 8) is a transmembrane protein with different functions. It plays an important role in tumors and neuroinflammation-related diseases. However, the role and molecular mechanism of ADAM8 in cerebral ischemia injury are still unclear. This study aims to evaluate the role of ADAM8 in cerebral ischemic injury and explore its signal transduction mechanism. This experiment shows that ADAM8 can significantly cause neurological deficits in MCAO mice and can substantially cause ipsilateral cerebral edema and cerebral infarction in MCAO mice. In addition, ADAM8 can significantly induce cortical cell apoptosis in MCAO mice, leading to the loss of neurons and the expression of proinflammatory factors COX2, iNOS, TNFα, and IL-6. Importantly, we confirmed that ADAM8 mediates the inflammatory response by promoting the activation of NLRP3 inflammasome, microglia, and astrocytes. These results indicate that ADAM8 may be a candidate drug target for the prevention and treatment of the cerebral ischemic injury.

On the Role of the Excitation/Inhibition Balance of Homeostatic Artificial Neural Networks

Homeostatic models of artificial neural networks have been developed to explain the self-organization of a stable dynamical connectivity between the neurons of the net. These models are typically two-population models, with excitatory and inhibitory cells. In these models, connectivity is a means to regulate cell activity, and in consequence, intracellular calcium levels towards a desired target level. The excitation/inhibition (E/I) balance is usually set to 80:20, a value characteristic for cortical cell distributions. We study the behavior of these homeostatic models outside of the physiological range of the E/I balance, and we find a pronounced bifurcation at about the physiological value of this balance. Lower inhibition values lead to sparsely connected networks. At a certain threshold value, the neurons develop a reasonably connected network that can fulfill the homeostasis criteria in a stable way. Beyond the threshold, the behavior of the artificial neural network changes drastically, with failing homeostasis and in consequence with an exploding number of connections. While the exact value of the balance at the bifurcation point is subject to the parameters of the model, the existence of this bifurcation might explain the stability of a certain E/I balance across a wide range of biological neural networks. Assuming that this class of models describes the self-organization of biological network connectivity reasonably realistically, the omnipresent physiological balance might represent a case of self-organized criticality in order to obtain a good connectivity while allowing for a stable intracellular calcium homeostasis.

Multi-Frequency Image Completion via a Biologically-Inspired Sub-Riemannian Model with Frequency and Phase

We present a novel cortically-inspired image completion algorithm. It uses five-dimensional sub-Riemannian cortical geometry, modeling the orientation, spatial frequency and phase-selective behavior of the cells in the visual cortex. The algorithm extracts the orientation, frequency and phase information existing in a given two-dimensional corrupted input image via a Gabor transform and represents those values in terms of cortical cell output responses in the model geometry. Then, it performs completion via a diffusion concentrated in a neighborhood along the neural connections within the model geometry. The diffusion models the activity propagation integrating orientation, frequency and phase features along the neural connections. Finally, the algorithm transforms the diffused and completed output responses back to the two-dimensional image plane.

Improved alpha-beta power reduction via combined electrical and ultrasonic stimulation in a parkinsonian cortex-basal ganglia-thalamus computational model

Objective. To investigate computationally the interaction of combined electrical and ultrasonic modulation of isolated neurons and of the Parkinsonian cortex-basal ganglia-thalamus loop. Approach. Continuous-wave or pulsed electrical and ultrasonic neuromodulation is applied to isolated Otsuka plateau-potential generating subthalamic nucleus (STN) and Pospischil regular, fast and low-threshold spiking cortical cells in a temporally alternating or simultaneous manner. Similar combinations of electrical/ultrasonic waveforms are applied to a Parkinsonian biophysical cortex-basal ganglia-thalamus neuronal network. Ultrasound-neuron interaction is modelled respectively for isolated neurons and the neuronal network with the NICE and SONIC implementations of the bilayer sonophore underlying mechanism. Reduction in α-β spectral energy is used as a proxy to express improvement in Parkinson’s disease by insonication and electrostimulation. Main results. Simultaneous electro-acoustic stimulation achieves a given level of neuronal activity at lower intensities compared to the separate stimulation modalities. Conversely, temporally alternating stimulation with 50 Hz electrical and ultrasound pulses is capable of eliciting 100 Hz STN firing rates. Furthermore, combination of ultrasound with hyperpolarizing currents can alter cortical cell relative spiking regimes. In the Parkinsonian neuronal network, continuous-wave and pulsed ultrasound reduce pathological oscillations by different mechanisms. High-frequency pulsed separated electrical and ultrasonic deep brain stimulation (DBS) reduce pathological α-β power by entraining STN-neurons. In contrast, continuous-wave ultrasound reduces pathological oscillations by silencing the STN. Compared to the separated stimulation modalities, temporally simultaneous or alternating electro-acoustic stimulation can achieve higher reductions in α-β power for the same safety contraints on electrical/ultrasonic intensity. Significance. Focused ultrasound has the potential of becoming a non-invasive alternative of conventional DBS for the treatment of Parkinson’s disease. Here, we elaborate on proposed benefits of combined electro-acoustic stimulation in terms of improved dynamic range, efficiency, spatial resolution, and neuronal selectivity.

The Anaphase Promoting Complex/Cyclosome Subunit 11 and Its Role in Organ Size and Plant Development

The anaphase promoting complex/cyclosome (APC/C), a member of the E3 ubiquitin ligase family, plays an important role in recognizing the substrates to be ubiquitylated. Progression of anaphase, and therefore, of the cell cycle, is coordinated through cyclin degradation cycles dependent on proteolysis triggered by APC/C. The APC/C activity depends on the formation of a pocket comprising the catalytic subunits, APC2, APC11, and APC10. Among these, the role of APC11 outside the cell division cycle is poorly understood. Therefore, the goal of this work was to analyze the function of APC11 during plant development by characterizing apc11 knock-down mutant lines. Accordingly, we observed decreased apc11 expression in the mutant lines, followed by a reduction in meristem root size based on the cortical cell length, and an overall size diminishment throughout the development. Additionally, crosses of apc11-1 and amiR-apc11 with plants carrying a WUSCHEL-RELATED HOMEOBOX5 (WOX5) fluorescent marker showed a weakening of the green fluorescent protein-positive cells in the Quiescent Center. Moreover, plants with apc11-1 show a decreased leaf area, together with a decrease in the cell area when the shoot development was observed by kinematics analysis. Finally, we observed a decreased APC/C activity in the root and shoot meristems in crosses of pCYCB1;1:D-box-GUS with apc11-1 plants. Our results indicate that APC11 is important in the early stages of development, mediating meristematic architecture through APC/C activity affecting the overall plant growth.