Neural Representations of Post-Decision Accuracy and Reward Expectation in the Caudate Nucleus and Frontal Eye Field.

Performance monitoring that supports ongoing behavioral adjustments is often examined in the context of either choice confidence for perceptual decisions (i.e., "did I get it right?") or reward expectation for reward-based decisions (i.e., "what reward will I receive?"). However, our understanding of how the brain encodes these distinct evaluative signals remains limited because they are easily conflated, particularly in commonly used two-alternative tasks with symmetric rewards for correct choices. Previously we used a motion-discrimination task with asymmetric rewards to identify neural substrates of forming reward-biased perceptual decisions in the caudate nucleus (part of the striatum in the basal ganglia) and the frontal eye field (FEF, in prefrontal cortex). Here we leveraged this task design to partially decouple estimates of accuracy and reward expectation and examine their impacts on subsequent decisions and their representations in those two brain areas. We identified distinguishable representations of these two evaluative signals in individual caudate and FEF neurons, with regional differences in their distribution patterns and time courses. We observed that well-trained monkeys (both sexes) used both evaluative signals, infrequently but consistently, to adjust their subsequent decisions. We found further that these behavioral adjustments had reliable relationships with the neural representations of both evaluative signals in caudate, but not FEF. These results suggest that the cortico-striatal decision network may use diverse evaluative signals to monitor and adjust decision-making behaviors, adding to our understanding of the different roles that the FEF and caudate nucleus play in a diversity of decision-related computations.

Forest-to-Cropland Conversion Reshapes Microbial Hierarchical Interactions and Degrades Ecosystem Multifunctionality at a National Scale.

Conversion from natural lands to cropland, primarily driven by agricultural expansion, could significantly alter soil microbiome worldwide; however, influences of forest-to-cropland conversion on microbial hierarchical interactions and ecosystem multifunctionality have not been fully understood. Here, we examined the effects of forest-to-cropland conversion on intratrophic and cross-trophic microbial interactions and soil ecosystem multifunctionality and further disclosed their underlying drivers at a national scale, using Illumina sequencing combined with high-throughput quantitative PCR techniques. The forest-to-cropland conversion significantly changed the structure of soil microbiome (including prokaryotic, fungal, and protistan communities) while it did not affect its alpha diversity. Both intrakingdom and interkingdom microbial networks revealed that the intratrophic and cross-trophic microbial interaction patterns generally tended to be more modular to resist environmental disturbance introduced from forest-to-cropland conversion, but this was insufficient for the cross-trophic interactions to maintain stability; hence, the protistan predation behaviors were still disturbed under such conversion. Moreover, key soil microbial clusters were declined during the forest-to-cropland conversion mainly because of the increased soil total phosphorus level, and this drove a great degradation of the ecosystem multifunctionality (by 207%) in cropland soils. Overall, these findings comprehensively implied the negative effects of forest-to-cropland conversion on the agroecosystem, from microbial hierarchical interactions to ecosystem multifunctionality.

Biological Interactions Mediate Soil Functions by Altering Rare Microbial Communities.

Soil microbes, the main driving force of terrestrial biogeochemical cycles, facilitate soil organic matter turnover. However, the influence of the soil fauna on microbial communities remains poorly understood. We investigated soil microbiota dynamics by introducing competition and predation among fauna into two soil ecosystems with different fertilization histories. The interactions significantly affected rare microbial communities including bacteria and fungi. Predation enhanced the abundance of C/N cycle-related genes. Rare microbial communities are important drivers of soil functional gene enrichment. Key rare microbial taxa, including SM1A02, Gammaproteobacteria, and HSB_OF53-F07, were identified. Metabolomics analysis suggested that increased functional gene abundance may be due to specific microbial metabolic activity mediated by soil fauna interactions. Predation had a stronger effect on rare microbes, functional genes, and microbial metabolism compared to competition. Long-term organic fertilizer application increased the soil resistance to animal interactions. These findings provide a comprehensive understanding of microbial community dynamics under soil biological interactions, emphasizing the roles of competition and predation among soil fauna in terrestrial ecosystems.

Application of data mining to minimize fire-induced domino effect risks.

Data mining (DM) has been applied in many advanced science and technology fields, but it has still not been used for domino effect risk management to explore minimum risk scenarios. This work investigates the feasibility of DM in minimizing the risk of fire-induced domino effects in chemical processing facilities. Based on DM, an evidential failure mode and effects analysis (E-FMEA), which could bridge chemical facilities' operational reliability and domino effect risk, is combined with fault tree analysis (FTA) for the occurrence risk modeling of loss of containment (LOC) event of chemical facilities, which is often the triggering point of fire-induced domino effects. Industry specific data such as reliability data, inspection records, and maintenance records are of great value to model the potential occurrence criticality of LOC. The data are used to characterize the LOC risk priority number (RPN) of chemical facilities through FTA and E-FMEA, search and statistics rules are proposed to mine inspection records to assess LOC risk factors. According to the RPN scores of facilities, inherent safety strategies to minimize risk via inventory control are proposed, and their effectiveness is tested using a well-known probit model. In this way, the approach proposes a unit-specific evidence-based risk minimization strategy for fire-induced domino effects. A case study demonstrates the capability of DM in the risk minimization of fire-induced domino effects.

Seipin regulates lipid homeostasis by ensuring calcium-dependent mitochondrial metabolism.

Seipin, the gene that causes Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), is important for adipocyte differentiation and lipid homeostasis. Previous studies in Drosophila revealed that Seipin promotes ER calcium homeostasis through the Ca2+-ATPase SERCA, but little is known about the events downstream of perturbed ER calcium homeostasis that lead to decreased lipid storage in Drosophila dSeipin mutants. Here, we show that glycolytic metabolites accumulate and the downstream mitochondrial TCA cycle is impaired in dSeipin mutants. The impaired TCA cycle further leads to a decreased level of citrate, a critical component of lipogenesis. Mechanistically, Seipin/SERCA-mediated ER calcium homeostasis is important for maintaining mitochondrial calcium homeostasis. Reduced mitochondrial calcium in dSeipin mutants affects the TCA cycle and mitochondrial function. The lipid storage defects in dSeipin mutant fat cells can be rescued by replenishing mitochondrial calcium or by restoring the level of citrate through genetic manipulations or supplementation with exogenous metabolites. Together, our results reveal that Seipin promotes adipose tissue lipid storage via calcium-dependent mitochondrial metabolism.

Phosphatidylserine synthase regulates cellular homeostasis through distinct metabolic mechanisms.

Phosphatidylserine (PS), synthesized in the endoplasmic reticulum (ER) by phosphatidylserine synthase (PSS), is transported to the plasma membrane (PM) and mitochondria through distinct routes. The in vivo functions of PS at different subcellular locations and the coordination between different PS transport routes are not fully understood. Here, we report that Drosophila PSS regulates cell growth, lipid storage and mitochondrial function. In pss RNAi, reduced PS depletes plasma membrane Akt, contributing to cell growth defects; the metabolic shift from phospholipid synthesis to neutral lipid synthesis results in ectopic lipid accumulation; and the reduction of mitochondrial PS impairs mitochondrial protein import and mitochondrial integrity. Importantly, reducing PS transport from the ER to PM by loss of PI4KIIIα partially rescues the mitochondrial defects of pss RNAi. Together, our results uncover a balance between different PS transport routes and reveal that PSS regulates cellular homeostasis through distinct metabolic mechanisms.

Genome annotation with long RNA reads reveals new patterns of gene expression and improves single-cell analyses in an ant brain.

BACKGROUND: Functional genomic analyses rely on high-quality genome assemblies and annotations. Highly contiguous genome assemblies have become available for a variety of species, but accurate and complete annotation of gene models, inclusive of alternative splice isoforms and transcription start and termination sites, remains difficult with traditional approaches. RESULTS: Here, we utilized full-length isoform sequencing (Iso-Seq), a long-read RNA sequencing technology, to obtain a comprehensive annotation of the transcriptome of the ant Harpegnathos saltator. The improved genome annotations include additional splice isoforms and extended 3' untranslated regions for more than 4000 genes. Reanalysis of RNA-seq experiments using these annotations revealed several genes with caste-specific differential expression and tissue- or caste-specific splicing patterns that were missed in previous analyses. The extended 3' untranslated regions afforded great improvements in the analysis of existing single-cell RNA-seq data, resulting in the recovery of the transcriptomes of 18% more cells. The deeper single-cell transcriptomes obtained with these new annotations allowed us to identify additional markers for several cell types in the ant brain, as well as genes differentially expressed across castes in specific cell types. CONCLUSIONS: Our results demonstrate that Iso-Seq is an efficient and effective approach to improve genome annotations and maximize the amount of information that can be obtained from existing and future genomic datasets in Harpegnathos and other organisms.

Long-Term Fertilization Shapes the Putative Electrotrophic Microbial Community in Paddy Soils Revealed by Microbial Electrosynthesis Systems.

Electrotrophs play an important role in biogeochemical cycles, but the effects of long-term fertilization on electrotrophic communities in paddy soils remain unclear. Here, we explored the responses of electrotrophic communities in paddy soil-based microcosms to different long-term fertilization practices using microbial electrosynthesis systems (MESs), high-throughput quantitative PCR, and 16s rRNA gene-based Illumina sequencing techniques. Compared to the case in the unfertilized soil (CK), applications of only manure (M); only chemical nitrogen, phosphorous, and potassium fertilizers (NPK); and M plus NPK (MNPK) clearly changed the electrotrophic bacterial community structure. The Streptomyces genus of the Actinobacteria phylum was the dominant electrotroph in the CK, M, and MNPK soils. The latter two soils also favored Truepera of Deinococcus-Thermus or Arenimonas and Thioalkalispira of Proteobacteria. Furthermore, Pseudomonas of Proteobacteria and Bacillus of Firmicutes were major electrotrophs in the NPK soil. These electrotrophs consumed biocathodic currents coupled with nitrate reduction and recovered 18-38% of electrons via dissimilatory nitrate reduction to ammonium (DNRA). The increased abundances of the nrfA gene for DNRA induced by electrical potential further supported that the electrotrophs enhanced DNRA for all soils. These expand our knowledge about the diversity of electrotrophs and their roles in N cycle in paddy soils and highlight the importance of fertilization in shaping electrotrophic communities.

Xanthine oxidase inhibitory peptides derived from tuna protein: virtual screening, inhibitory activity, and molecular mechanisms.

BACKGROUND: There has been growing interest in the use of xanthine oxidase (XO) as a therapeutic agent to prevent gout and hyperuricemia. In the present study, XO inhibitory peptides were identified from tuna protein by virtual screening, and molecular docking was used to elicit the interaction mechanism between XO and peptides. RESULTS: A novel tetrapeptide, EEAK, exhibited high XO inhibitory activity with an IC50 of 173.00 ± 0.06 µM. Molecular docking analysis revealed that EEAK bound with the pivotal residues of XO's active sites (i.e., Glu802, Arg880, Glu1261) through two conventional hydrogen bond interactions, two attractive charge interactions, and one salt bridge. EEAK could also bind with the residues Phe649, Leu648, Lys771, Ser876, Phe914, and Thr1010 of XO. CONCLUSION: This study suggested that conventional hydrogen bond interactions and electrostatic interactions play an important role in XO inhibition. The novel XO inhibitory peptide EEAK from tuna protein could be used as potential candidate for controlling gout and hyperuricemia. © 2020 Society of Chemical Industry.

Identification of ovalbumin-derived peptides as multi-target inhibitors of AChE, BChE, and BACE1.

BACKGROUND: Alzheimer's disease (AD) is a kind of progressive neurodegenerative disease that affects the elderly. There is no ideal treatment for AD. Thus, the purpose of this study is to identify anti-AD peptides from ovalbumin. RESULTS: The potential tripeptides IEK, LYR, and CIK were selected for molecular docking. The '-CDOCKER_Energy' values of the best docking positions of the tripeptide IEK, LYR, and CIK interacting with acetylcholinesterase (AChE) were 93.8119, 86.9556 and 73.6370 kcal mol-1 , respectively. The '-CDOCKER_Energy' values for interaction with butyrylcholinesterase (BChE) were 96.6386, 80.8392, and 87.4341 kcal mol-1 , respectively. Most importantly, the '-CDOCKER_Energy' values for interaction with ß-site amyloid precursor protein cleavage enzyme1 (BACE1) were 85.5903, 71.3342, and 68.4290 kcal mol-1 , respectively. Overall, in vitro assay results demonstrated that the peptide CIK exhibited impressive inhibitory activities against AChE, BChE, and BACE1, with half maximal inhibitory concentration (IC50 ) values of 6.76, 7.72, and 34.48 µmol L-1 , respectively. In particular, CIK can be joined with some peripheral anion sites (PAS) and catalytic sites on AChE, BChE, and BACE1. CONCLUSION: Tripeptide CIK can effectively inhibit the activities of AChE, BChE, and BACE1. Tripeptide CIK therefore has the potential to treat AD effectively. © 2020 Society of Chemical Industry.

Fate of Labile Organic Carbon in Paddy Soil Is Regulated by Microbial Ferric Iron Reduction.

Global paddy soil is the primary source of methane, a potent greenhouse gas. It is therefore highly important to understand the carbon cycling in paddy soil. Microbial reduction of iron, which is widely found in paddy soil, is likely coupled with the oxidation of dissolved organic matter (DOM) and suppresses methanogenesis. However, little is known about the biotransformation of small molecular DOM accumulated under flooded conditions and the effect of iron reduction on the biotransformation pathway. Here, we carried out anaerobic incubation experiments using field-collected samples amended with ferrihydrite and different short-chain fatty acids. Our results showed that less than 20% of short-chain fatty acids were mineralized and released to the atmosphere. Using Fourier transform ion cyclotron resonance mass spectrometry, we further found that a large number of recalcitrant molecules were produced during microbial consumption of these short-chain fatty acids. Moreover, the biotransformation efficiency of short-chain fatty acids decreased with the increasing length of carbon chains. Ferrihydrite addition promoted microbial assimilation of short-chain fatty acids as well as enhanced the activation and biotransformation of indigenous stable carbon in the soil replenished with formate. This study demonstrates the significance of ferrihydrite in the biotransformation of labile DOM and promotes a more comprehensive understanding of the coupling of iron reduction and carbon cycling in paddy soils.

Biochar Modulates Methanogenesis through Electron Syntrophy of Microorganisms with Ethanol as a Substrate.

Biochar has the potential to influence methanogenesis which is a key component of global carbon cycling. However, the mechanisms governing biochar's influence on methanogenesis is not well understood, especially its effects on interspecies relationships between methanogens and anaerobic bacteria (e.g., Geobacteraceae). To understand how different types of biochar influence methanogenesis, biochars derived from rice straw (RB), wood chips (WB), and manure (MB) were added to the methanogenic enrichment culture system of a paddy soil. Compared to the nonbiochar control, RB and MB additions accelerated methanogenesis remarkably, showing 10.7 and 12.3-folds higher methane production rate, respectively; while WB had little effect on methanogenesis. Using Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and electrochemical methods, RB and MB also had higher redox-active properties or charging and discharging capacities than WB, and the functional groups, mainly quinones, on the biochar surface played an important role in facilitating methanogenesis. Quantitative polymerase chain reaction results demonstrated that electronic syntrophy did exist between methanogens and Geobacteraceae. RB and MB stimulate methanogenesis by facilitating direct interspecies electron transfer between methanogens and Geobacteraceae. Our findings contribute to a better understanding of the effects of biochars from different feedstocks on methanogenesis and provide new evidence to the mechanisms of stimulating methanogenesis via biochar.

Increased microbial functional diversity under long-term organic and integrated fertilization in a paddy soil.

Microbes play key roles in diverse biogeochemical processes including nutrient cycling. However, responses of soil microbial community and functional genes to long-term integrated fertilization (chemical combined with organic fertilization) remain unclear. Here, we used pyrosequencing and a microarray-based GeoChip to explore the shifts of microbial community and functional genes in a paddy soil which received over 21-year fertilization with various regimes, including control (no fertilizer), rice straw (R), rice straw plus chemical fertilizer nitrogen (NR), N and phosphorus (NPR), NP and potassium (NPKR), and reduced rice straw plus reduced NPK (L-NPKR). Significant shifts of the overall soil bacterial composition only occurred in the NPKR and L-NPKR treatments, with enrichment of certain groups including Bradyrhizobiaceae and Rhodospirillaceae families that benefit higher productivity. All fertilization treatments significantly altered the soil microbial functional structure with increased diversity and abundances of genes for carbon and nitrogen cycling, in which NPKR and L-NPKR exhibited the strongest effect, while R exhibited the least. Functional gene structure and abundance were significantly correlated with corresponding soil enzymatic activities and rice yield, respectively, suggesting that the structural shift of the microbial functional community under fertilization might promote soil nutrient turnover and thereby affect yield. Overall, this study indicates that the combined application of rice straw and balanced chemical fertilizers was more pronounced in shifting the bacterial composition and improving the functional diversity toward higher productivity, providing a microbial point of view on applying a cost-effective integrated fertilization regime with rice straw plus reduced chemical fertilizers for sustainable nutrient management.

Short- and long-term antihypertensive effect of egg protein-derived peptide QIGLF.

BACKGROUND: The present study aimed to investigate the in vivo antihypertensive effect on spontaneously hypertensive rats (SHRs) induced by egg protein-derived peptide QIGLF, which has been previously characterized in vitro as a potent angiotensin-converting enzyme inhibitor. RESULTS: In vivo antihypertensive effect of QIGLF orally administered was evaluated by the tail-cuff method. The systolic blood pressure and the diastolic blood pressure of rats were measured 0, 5, 10, 15 and 20 h after administration every day. Subsequently, the effect of QIGLF on angiotensin-converting enzyme mRNA expression in the kidney of SHRs was evaluated by a polymerase chain reaction. Systolic blood pressure was found to be reduced markedly in the SHRs after a single oral administration. CONCLUSION: The results show that the effect of QIGLF (50 mg kg-1 body weight) was similar to that of captopril (10 mg kg-1 body weight) with respect to lowering systolic blood pressure in SHRs. Therefore, egg white protein-derived peptide QIGLF may be useful in the prevention or treatment of hypertension. © 2016 Society of Chemical Industry.

Regiodivergent Enantioselective γ-Additions of Oxazolones to 2,3-Butadienoates Catalyzed by Phosphines: Synthesis of α,α-Disubstituted α-Amino Acids and N,O-Acetal Derivatives.

Phosphine-catalyzed regiodivergent enantioselective C-2- and C-4-selective γ-additions of oxazolones to 2,3-butadienoates have been developed. The C-4-selective γ-addition of oxazolones occurred in a highly enantioselective manner when 2-aryl-4-alkyloxazol-5-(4H)-ones were employed as pronucleophiles. With the employment of 2-alkyl-4-aryloxazol-5-(4H)-ones as the donor, C-2-selective γ-addition of oxazolones took place in a highly enantioselective manner. The C-4-selective adducts provided rapid access to optically enriched α,α-disubstituted α-amino acid derivatives, and the C-2-selective products led to facile synthesis of chiral N,O-acetals and γ-lactols. Theoretical studies via DFT calculations suggested that the origin of the observed regioselectivity was due to the distortion energy that resulted from the interaction between the nucleophilic oxazolide and the electrophilic phosphonium intermediate.

Digestion and absorption of an egg white ACE-inhibitory peptide in human intestinal Caco-2 cell monolayers.

The objective of this study was to investigate the digestion and absorption of egg white-derived angiotensin I-converting enzyme (ACE)-inhibitory peptide TNGIIR in human intestinal Caco-2 cell monolayers. Results showed that the digestion of TNGIIR to simulated gastrointestinal enzymes and brush border membrane peptidases were 5.87% ± 1.92% and 17.17% ± 0.64%, respectively (p < 0.05). The apparent permeability coefficients (P(app)) of TNGIIR from the apical to basolateral side in Caco-2 cell monolayers was determined to be (4.92 ± 0.40) × 10(-6) cm/s, indicating that TNGIIR can transport across Caco-2 cell monolayers in intact form. In addition, only cytochalasin D, a disruptor of tight junctions (TJs), changed TNGIIR transport rate significantly (p < 0.05), suggesting that the main transport route for TNGIIR across Caco-2 cell monolayers was paracellular pathway via TJs.

Distinct dynamics of ramping activity in the frontal cortex and caudate nucleus in monkeys.

The prefronto-striatal network is involved in many cognitive functions, including perceptual decision making and reward-modulated behaviors. For well-trained subjects, neural responses frequently show similar patterns in the prefrontal cortex and striatum, making it difficult to tease apart distinct regional contributions. Here I show that, despite similar mean firing rate patterns, prefrontal and striatal responses differ in other temporal dynamics for both perceptual and reward-based tasks. Compared with simulation results, the temporal dynamics of prefrontal activity are consistent with an accumulation of sensory evidence used to solve a perceptual task but not with an accumulation of reward context-related information used for the development of a reward bias. In contrast, the dynamics of striatal activity is consistent with an accumulation of reward context-related information and with an accumulation of sensory evidence during early stimulus viewing. These results suggest that prefrontal and striatal neurons may have specialized functions for different tasks even with similar average activity.

Long-term balanced fertilization increases the soil microbial functional diversity in a phosphorus-limited paddy soil.

The influence of long-term chemical fertilization on soil microbial communities has been one of the frontier topics of agricultural and environmental sciences and is critical for linking soil microbial flora with soil functions. In this study, 16S rRNA gene pyrosequencing and a functional gene array, geochip 4.0, were used to investigate the shifts in microbial composition and functional gene structure in paddy soils with different fertilization treatments over a 22-year period. These included a control without fertilizers; chemical nitrogen fertilizer (N); N and phosphate (NP); N and potassium (NK); and N, P and K (NPK). Based on 16S rRNA gene data, both species evenness and key genera were affected by P fertilization. Functional gene array-based analysis revealed that long-term fertilization significantly changed the overall microbial functional structures. Chemical fertilization significantly increased the diversity and abundance of most genes involved in C, N, P and S cycling, especially for the treatments NK and NPK. Significant correlations were found among functional gene structure and abundance, related soil enzymatic activities and rice yield, suggesting that a fertilizer-induced shift in the microbial community may accelerate the nutrient turnover in soil, which in turn influenced rice growth. The effect of N fertilization on soil microbial functional genes was mitigated by the addition of P fertilizer in this P-limited paddy soil, suggesting that balanced chemical fertilization is beneficial to the soil microbial community and its functions.

Isolation and characterisation of in vitro and cellular free radical scavenging peptides from corn peptide fractions.

Corn gluten meal, a corn processing industry by-product, is a good source for the preparation of bioactive peptides due to its special amino acid composition. In the present study, the in vitro and cellular free radical scavenging activities of corn peptide fractions (CPFs) were investigated. Results indicated that CPF1 (molecular weight less than 1 kDa) and CPF2 (molecular weight between 1 and 3 kDa) exhibited good hydroxyl radical, superoxide anion radical and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonicacid) diammonium salt (ABTS) radical scavenging activity and oxygen radical absorbance capacity (ORAC). Meanwhile, the in vitro radical scavenging activity of CPF1 was slightly higher than that of CPF2. Both CPF1 and CPF2 also exhibited significant cytoprotective effects and intracellular reactive oxygen species scavenging activity in Caco-2 cells exposed to hydrogen peroxide (H2O2). The amino acid composition analysis revealed that the CPF were rich in hydrophobic amino acids, which comprised of more than 45% of total amino acids. An antioxidant peptide sequence of Tyr-Phe-Cys-Leu-Thr (YFCLT) was identified from CPF1 using matrix-assisted laser desorption/ionization time-of-flight/time-of-flight mass spectrometry (MALDI TOF/TOF MS). The YFCLT exhibited excellent ABTS radical scavenging activity with a 50% effective concentration (EC50) value of 37.63 µM, which was much lower than that of Trolox. In conclusion, corn gluten meal might be a good source to prepare antioxidant peptides.

Modality-based organization of ascending somatosensory axons in the direct dorsal column pathway.

The long-standing doctrine regarding the functional organization of the direct dorsal column (DDC) pathway is the "somatotopic map" model, which suggests that somatosensory afferents are primarily organized by receptive field instead of modality. Using modality-specific genetic tracing, here we show that ascending mechanosensory and proprioceptive axons, two main types of the DDC afferents, are largely segregated into a medial-lateral pattern in the mouse dorsal column and medulla. In addition, we found that this modality-based organization is likely to be conserved in other mammalian species, including human. Furthermore, we identified key morphological differences between these two types of afferents, which explains how modality segregation is formed and why a rough "somatotopic map" was previously detected. Collectively, our results establish a new functional organization model for the mammalian direct dorsal column pathway and provide insight into how somatotopic and modality-based organization coexist in the central somatosensory pathway.