ABSTRACT
The canonical microcircuit (CMC) has been hypothesized to be the fundamental unit of information processing in cortex. Each CMC unit is thought to be an interconnected column of neurons with specific connections between excitatory and inhibitory neurons across layers. Recently, we identified a conserved spectrolaminar motif of oscillatory activity across the primate cortex that may be the physiological consequence of the CMC. The spectrolaminar motif consists of local field potential (LFP) gamma-band power (40-150 Hz) peaking in superficial layers 2 and 3 and alpha/beta-band power (8-30 Hz) peaking in deep layers 5 and 6. Here, we investigate whether specific conserved cell types may produce the spectrolaminar motif. We collected laminar histological and electrophysiological data in 11 distinct cortical areas spanning the visual hierarchy: V1, V2, V3, V4, TEO, MT, MST, LIP, 8A/FEF, PMD, and LPFC (area 46), and anatomical data in DP and 7A. We stained representative slices for the three main inhibitory subtypes, Parvalbumin (PV), Calbindin (CB), and Calretinin (CR) positive neurons, as well as pyramidal cells marked with Neurogranin (NRGN). We found a conserved laminar structure of PV, CB, CR, and pyramidal cells. We also found a consistent relationship between the laminar distribution of inhibitory subtypes with power in the local field potential. PV interneuron density positively correlated with gamma (40-150 Hz) power. CR and CB density negatively correlated with alpha (8-12 Hz) and beta (13-30 Hz) oscillations. The conserved, layer-specific pattern of inhibition and excitation across layers is therefore likely the anatomical substrate of the spectrolaminar motif. Significance Statement: Neuronal oscillations emerge as an interplay between excitatory and inhibitory neurons and underlie cognitive functions and conscious states. These oscillations have distinct expression patterns across cortical layers. Does cellular anatomy enable these oscillations to emerge in specific cortical layers? We present a comprehensive analysis of the laminar distribution of the three main inhibitory cell types in primate cortex (Parvalbumin, Calbindin, and Calretinin positive) and excitatory pyramidal cells. We found a canonical relationship between the laminar anatomy and electrophysiology in 11 distinct primate areas spanning from primary visual to prefrontal cortex. The laminar anatomy explained the expression patterns of neuronal oscillations in different frequencies. Our work provides insight into the cortex-wide cellular mechanisms that generate neuronal oscillations in primates.
ABSTRACT
The development of antimicrobial agents with novel model of actions is a promising strategy to combat multiple resistant bacteria. Here, three ruthenium-based complexes, which acted as potential antimicrobial agents, were synthesized and characterized. Importantly, three complexes all showed strong bactericidal potency against Staphylococcus aureus. In particular, the most active one has a MIC of 6.25 µg/mL. Mechanistic studies indicated that ruthenium complex killed S. aureus by releasing ROS and damaging the integrity of bacterial cell membrane. In addition, the most active complex not only could inhibit the biofilm formation and hemolytic toxin secretion of S. aureus, but also serve as a potential antimicrobial adjuvant as well, which showed synergistic effects with eight traditional antibiotics. Finally, both G. mellonella larva infection model and mouse skin infection model all demonstrated that ruthenium complex also showed significant efficacy against S. aureus inâ vivo. In summary, our study suggested that ruthenium-based complexes bearing a phenyl hydroxide are promising antimicrobial agents for combating S. aureus.
Subject(s)
Anti-Infective Agents , Ruthenium , Staphylococcal Infections , Animals , Mice , Staphylococcus aureus , Ruthenium/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology , Phenol , Staphylococcal Infections/drug therapy , Bacteria , HydroxidesABSTRACT
This study aimed to explore the relationship between genetic changes and high-altitude pulmonary edema (HAPE) susceptibility, and to screen for the key single nucleotide polymorphism (SNP) loci in the HAPE-susceptibility gene, by investigating the SNPs occurring in hypoxia-related genes in HAPE-susceptible and control (non-susceptible) populations. This research was conducted on Han recruits, who travelled to the Lhasa plateau (altitude, 3658 m). Ten loci located on ten genes extracted from the HAPE and healthy populations were amplified by polymerase chain reaction, and subsequently sequenced. The investigated genes included those coding for aldosterone synthase 2 (CYP11B2), angiotensin-converting enzyme (ACE), heat-shock protein 70 (HSP70), nuclear factor kappa B (NF-κB), surfactant protein A2 (SP-A2), plasminogen activator inhibitor-1 (PAI-1), nitric oxide synthetase (NOS), vascular endothelial growth factor (VEGF), prolyl hydroxylase (EGLN1), and zinc finger protein A20. The gene distribution of each SNP loci and its correlation with HAPE was analyzed. Statistical analyses of the genotype frequencies of the SNPs revealed significant differences in the ACE (rs4309), EGLN1 (rs480902), SP-A2 (rs1965708), HSP70 (rs1008438), PAI-1 (rs1799889), and NOS (rs199983) expressions between the HAPE and healthy control groups (P < 0.05); therefore, these SNP loci were believed to indicate HAPE susceptibility. HAPE is correlated with multiple- SNP loci. A correlation analysis between genetic polymorphism and HAPE susceptibility revealed that 6 hypoxia-related genes were key sites accounting for HAPE. These findings could help assess the risk of HAPE in populations expressing different genotypes, in order to reduce the occurrence of HAPE.
Subject(s)
Altitude , Genetic Predisposition to Disease , Hypoxia/genetics , Polymorphism, Single Nucleotide/genetics , Pulmonary Edema/genetics , Acute Disease , Alleles , Base Sequence , DNA Mutational Analysis , DNA-Binding Proteins/genetics , Gene Frequency/genetics , Genetic Loci , HSP70 Heat-Shock Proteins/genetics , Heterozygote , Homozygote , Humans , Intracellular Signaling Peptides and Proteins/genetics , Molecular Sequence Data , NF-kappa B/genetics , Nitric Oxide Synthase/genetics , Nuclear Proteins/genetics , Peptidyl-Dipeptidase A/genetics , Plasminogen Activator Inhibitor 1/genetics , Prolyl Hydroxylases/genetics , Promoter Regions, Genetic/genetics , Pulmonary Surfactant-Associated Protein A/genetics , Tumor Necrosis Factor alpha-Induced Protein 3 , Vascular Endothelial Growth Factor A/geneticsABSTRACT
We study the dynamics of online learning in multilayer neural networks where training examples are sampled with repetition and where the number of examples scales with the number of network weights. The analysis is carried out using the dynamical replica method aimed at obtaining a closed set of coupled equations for a set of macroscopic variables from which both training and generalization errors can be calculated. We focus on scenarios whereby training examples are corrupted by additive Gaussian output noise and regularizers are introduced to improve the network performance. The dependence of the dynamics on the noise level, with and without regularizers, is examined, as well as that of the asymptotic values obtained for both training and generalization errors. We also demonstrate the ability of the method to approximate the learning dynamics in structurally unrealizable scenarios. The theoretical results show good agreement with those obtained from computer simulations.
Subject(s)
Learning , Models, Neurological , Algorithms , Artificial Intelligence , Computer Simulation , Generalization, Psychological , Models, Statistical , Neural Networks, Computer , Normal Distribution , Time FactorsABSTRACT
This paper presents a parameter estimation method for suspended sediment transport processes subject to random wave environments. An objective function was constructed based on measurements of suspended sediment concentration profiles and the governing equation of sediment transport. The Chebyshev least square method was employed to approximate the process parameters, i.e. vertical eddy diffusivity (epsilon) and net vertical velocity (w). The objective function of sediment transport processes with Chebyshev's parameters is well posed and does not require boundary conditions. First, second, and third order epsilon and w Chebyshev orthogonal functions were determined for monochromatic (MONO), narrow-banded (NBR) and broad-banded (BBR) random wave conditions. In the BBR and NBR conditions, the best fit Chebyshev approximations of epsilon and w were 2nd degree, while the best approximations in the MONO condition were 2nd degree for epsilon and 1st degree for w. The Chebyshev method provides a quick, accurate and direct estimation of two prime parameters in sediment transport dynamics.